[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"glioblastoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:glioblastoma":628},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,202,0,25,[9,54,84,114,138,171,195,216,237,247,266,300,323,342,361,383,399,427,448,469,487,514,554,576,606],{"id":10,"slug":4,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":26,"conditions":27,"keywords":29,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":42,"lastUpdatePostDateStruct":43,"startDateStruct":46,"completionDateStruct":48,"leadSponsor":50,"locationsCount":53},"100054096",false,"NCT03970447","A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma","GBM AGILE: Global Adaptive Trial Master Protocol: An International, Seamless Phase II\u002FIII Response Adaptive Randomization Platform Trial Designed To Evaluate Multiple Regimens In Newly Diagnosed and Recurrent GBM","GBM AGILE","Newly Diagnosed Inclusion Criteria:\n\n* Age ≥ 18 years.\n* Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry \\[IHC\\] or sequencing for IDH) established following either a surgical resection or biopsy. An MRI scan with the required imaging sequences performed within 21 days prior to randomization preferably. The post-operative MRI scan performed within 96 hours of surgery or the MRI scan performed for radiation therapy planning may serve as the MRI scan performed during screening if all required imaging sequences were obtained.\n* Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization.\n* Availability of tumor tissue representative of GBM from definitive surgery or biopsy.\n\nRecurrent Inclusion Criteria:\n\n* Age ≥ 18 years.\n* Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry \\[IHC\\] or sequencing for IDH) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum radiation therapy (RT).\n* Evidence of recurrent disease demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria.\n* Two scans to confirm progression are required: at least 1 scan at the time of progression and 1 scan prior to the time of progression.\n* Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization.\n* Availability of tumor tissue representative of GBM from initial definitive surgery and\u002For, recurrent surgery, if performed.\n\nNewly Diagnosed Exclusion Criteria:\n\n* Received any prior treatment for glioma including: a. Prior prolifeprospan 20 with carmustine wafer. b. Prior intracerebral, intratumoral, or cerebral spinal fluid (CSF) agent. c. Prior radiation treatment for GBM or lower-grade glioma. d. Prior chemotherapy or immunotherapy for GBM or lower-grade glioma. Receiving additional, concurrent, active therapy for GBM outside of the trial.\n* Extensive leptomeningeal disease.\n* QTc \\> 470 msec\n* History of another malignancy in the previous 2 years, with a disease-free interval of \\\u003C 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.\n\nRecurrent Exclusion Criteria:\n\n* Early disease progression prior to 3 months (12 weeks) from the completion of RT.\n* More than 2 prior lines for chemotherapy administration. (NOTE: In the 1st line adjuvant setting, combination of temozolomide (TMZ) with an experimental agent, is considered one line of chemotherapy.)\n* Received any prior treatment with lomustine, agents part of any of the experimental arms, and bevacizumab or other vascular endothelial growth factor (VEGF) or VEGF receptor-mediated targeted agent.\n* Any prior treatment with prolifeprospan 20 with carmustine wafer.\n* Any prior treatment with an intracerebral agent.\n* Receiving additional, concurrent, active therapy for GBM outside of the trial\n* Extensive leptomeningeal disease.\n* QTc \\> 470 msec\n* History of another malignancy in the previous 2 years, with a disease-free interval of \\\u003C 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.","ALL","18 Years",{"count":20,"type":21},2250,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE2","PHASE3","Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II\u002FIII response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM.\n\nAll institutions are enrolling Newly Diagnosed participants. Institutions also enrolling Recurrent participants are marked with an asterisk (\\*).",[28],"Glioblastoma",[28,30,31,32,33,34,35,36,37,38,39,40],"Newly diagnosed","recurrent","O6-methylguanine-DNA-methyltransferase (MGMT) methylated","MGMT unmethylated","isocitrate dehydrogenase (IDH) wild-type","Bayesian","adaptive randomization","Master Protocol","Platform Trial","Phase 2","Phase 3","RECRUITING","2026-07-10",{"date":44,"type":45},"2026-07-13","ACTUAL",{"date":47,"type":45},"2019-07-30",{"date":49,"type":21},"2030-06",{"name":51,"class":52},"Global Coalition for Adaptive Research","OTHER",63,{"id":55,"slug":4,"hasResults":11,"nctId":56,"briefTitle":57,"officialTitle":58,"acronym":59,"eligibilityCriteria":60,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":61,"targetDuration":4,"studyType":22,"phases":63,"briefSummary":64,"conditions":65,"keywords":68,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":73,"lastUpdatePostDateStruct":74,"startDateStruct":76,"completionDateStruct":78,"leadSponsor":80,"locationsCount":83},"100508572","NCT05902169","Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM","A Randomized, Open-label, Multicentric, Two-arm Pivotal Trial of SonoCloud-9 Combined With Carboplatin (CBDCA) vs Standard of Care Lomustine (CCNU) or Temozolomide (TMZ) in Patients Undergoing Planned Resection for First Recurrence Glioblastoma.","SONOBIRD","Inclusion Criteria:\n\n1. Histologically proven glioblastoma (WHO criteria 2021), absence of IDH mutation demonstrated by negative IDH1 R132H staining on Immunohistochemistry.\n2. Patient must have received prior first line therapy that must have contained both:\n\n   1. Prior surgery or biopsy and standard fractionated radiotherapy (1.8-2 Gy\u002Ffraction, \\>56 Gy\\\u003C66 Gy) or hypofractionated radiotherapy (15 x 2.66 Gy or similar regimen)\n   2. One line of maintenance chemotherapy and\u002For immune- or biological therapy, (with or without Tumor-Treating Fields)\n3. First, unequivocal disease progression with\n\n   1. measurable tumor (\\>100 mm2 or 1 cm3, based on RANO criteria) documented (e.g., increase of 25% in tumor diameter) on MRI performed within 14 days of inclusion and,\n   2. interval of a minimum of 12 weeks since the completion of prior radiotherapy, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling\n4. Patient is candidate for craniotomy and at least 50% resection of enhancing region\n5. Maximal enhancing tumor diameter prior to inclusion ≤ 5 cm on T1w. (In case of planned lobectomy, post operative peritumoral brain or residual size ≤5 cm)\n6. WHO performance status ≤ 2 (equivalent to Karnofsky Performance Status (KPS) ≥ 70)\n7. Age ≥ 18 years\n8. Participant must be recovered from acute toxic effects (\\\u003Cgrade 2) of all prior anticancer therapy. Interval since last therapy to presumed date of surgery of at least:\n\n   1. ≥ 4 weeks or 5 half-lives (whichever is shorter) for\n\n      * Cytotoxic\n      * Other small chemical entity (e.g., targeted therapy)\n      * For biologics (e.g., antibodies, except bevacizumab)\n   2. ≥ 6 weeks of prior bevacizumab\n9. Adequate hematologic, hepatic, and renal laboratory values within 14 days of inclusion i.e.:\n\n   1. Hemoglobin ≥ 10 g\u002FdL, platelets ≥ 100,000\u002Fmm3, neutrophils ≥ 1500\u002Fmm3.\n   2. Liver function test with ≤ grade 1 alterations, except if due to antiepileptic drug therapy or isolated increased bilirubin due to Gilbert syndrome\n   3. Estimated glomerular filtration rate (eGFR) of at least 60 mL\u002Fmin\u002F1.73 m2 using Cockcroft Gault formula\n10. Patient able to understand clinical trial information and willing to provide signed and informed consent\n11. Patient of childbearing potential must have a negative pregnancy test within 14 days of inclusion and must agree to use a medically-acceptable method of birth control during the treatment period and, if randomized in the experimental arm, for at least 1 month after the last cycle of carboplatin\n12. A male patient must agree to use condoms during the treatment period and, if randomized in the experimental arm, for at least 3 months after the last cycle of carboplatin; the patient must also refrain from donating sperm during this period.\n13. Patient must be a beneficiary of a health plan that covers routine patient care costs. Patient must be a beneficiary of or affiliated with a social security scheme (according to country-specific requirements)\n\nNon-Inclusion Criteria:\n\n1. Multifocal enhancing tumor on T1w (unless all localized in a 5 cm diameter area)\n2. Posterior fossa tumor\n3. Known BRAF\u002F NTKR mutated patients\n4. Patient at risk of surgery site infection (e.g., 2 or more previous craniotomies\u002Fneurosurgery within the last 3 months, poor skin condition, and\u002For previously infected surgical field, or any other condition that is of increased infectious risk in the opinion of the neurosurgeon)\n5. Patient treated at high, stable -or average- dose of corticosteroids (≥ 6 mg\u002Fday dexamethasone or equivalent) in the 7 days prior to inclusion. Patients on dexamethasone for reasons other than mass effect may still be enrolled.\n6. Contra-indication to carboplatin, CCNU or TMZ\n7. Known history of hypersensitivity reactions to perflutren lipid microsphere components or to any of the inactive ingredients in ultrasound resonator\n8. Patient has received bevacizumab for other reasons (such as tumor progression) than treating edema\n9. Peripheral neuropathy or neuropathy ≥ grade 2\n10. Uncontrolled epilepsy or evidence of intracranial pressure\n11. Patient with known intracranial aneurism or having presented intra-tumor significant spontaneous hemorrhage\n12. Patient with unremovable coils, clips, shunts, intravascular stents, and\u002For wafer, or reservoirs\n13. Patient with medical need to be on continued anti-platelet aggregation therapy and\u002For anticoagulation. Patients for whom anticoagulation\u002Fplatelet aggregation can be temporarily interrupted may be eligible after discussion and prior authorization by the sponsor.\n14. Patient receiving enzyme-inducing antiepileptic drugs (namely phenytoin, carbamazepine and derivatives, phenobarbital), unless switched on another antiepileptic regimen\n15. History of other malignancy within 3 years prior to study start with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma, non-melanomatous skin cancer or carcinoma in situ of the uterine cervix\n16. Patient with known or suspected active or chronic infections\n17. Patient with known significant cardiac disease, known to have right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure \\> 90 mm Hg), uncontrolled systemic hypertension, or acute respiratory distress syndrome\n18. Known sensitivity\u002Fallergy to gadolinium, or other intravascular contrast agents\n19. Patient with impaired thermo-regulation or temperature sensation\n20. Pregnant, or breastfeeding patient\n21. Any other serious patient medical or psychological condition that may interfere with adequate and safe delivery of treatment and care (e.g., positive human immunodeficiency virus \\[HIV\\] status, potential blood-borne infections,…), circumstance (e.g., sinus opening during surgery), psychological, morphological characteristics (e.g., skin characteristics, bone thickness), or any pre-existing comorbidities that in the investigator's opinion may prevent the implantation of the device, may impair the ability of the patient to receive treatment with SonoCloud-9 or may be confounding for evaluation of the clinical trial endpoints\n22. Patients under guardianship, curatorship, under legal protection or deprived of liberty by an administrative or judicial decision\n\nExclusion Criterion:\n\nOccurrence of any major medical illnesses or impairments that in the Investigator's opinion may hampered the ability of the patient to receive treatment with SonoCloud-9 or may be confounding for evaluation of the clinical endpoints.",{"count":62,"type":21},560,[25],"The brain is protected from any toxic or inflammatory molecule by the blood-brain barrier (BBB). This physical barrier is located at the level of the blood vessel walls. Because of these barrier properties, the blood vessels are also impermeable to the passage of therapeutic molecules from the blood to the brain. The development of effective treatments against glioblastoma is thus limited due to the BBB that prevents most drugs injected in the bloodstream from getting into brain tissue where the tumour is seated. The SonoCloud-9 (SC9) is an investigational device using ultrasound technology and specially developed to open the BBB in the area of and surrounding the tumour. The transient opening of the BBB allows more drugs to reach the brain tumour tissue. Carboplatin is a chemotherapy that is approved to treat different cancer types alone or in combination with other drugs, and has been used in the treatment of glioblastoma. Despite its proven efficacy in the laboratory on glioblastoma cells, carboplatin does not readily cross the BBB in humans. A clinical trial has shown that in combination with the SonoCloud-9, more carboplatin can reach the brain tumour tissue. The objective of the proposed trial is to show that the association - carboplatin with the SonoCloud-9 - will increase efficacy of the drug in patients with recurrent glioblastoma.",[28,66,67],"Recurrent Glioblastoma","GBM",[69,70,71,72],"carboplatin","SonoCloud","blood-brain barrier","Low Intensity Pulsed Ultrasound (LIPU)","2026-06-30",{"date":75,"type":45},"2026-07-01",{"date":77,"type":45},"2024-01-29",{"date":79,"type":21},"2028-06-30",{"name":81,"class":82},"CarThera","INDUSTRY",49,{"id":85,"slug":4,"hasResults":11,"nctId":86,"briefTitle":87,"officialTitle":87,"acronym":4,"eligibilityCriteria":88,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":89,"targetDuration":4,"studyType":22,"phases":91,"briefSummary":93,"conditions":94,"keywords":99,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":105,"lastUpdatePostDateStruct":106,"startDateStruct":107,"completionDateStruct":109,"leadSponsor":111,"locationsCount":113},"100630882","NCT07493447","Pilot Study Evaluating Panitumumab-IRDye800 as an Optical Imaging Agent to Detect Intracranial Lesions During Neurosurgical Procedures","Inclusion Criteria:\n\n* Subjects with intracranial lesions undergoing surgical removal as their standard of care will be eligible. These may include subjects status post chemotherapy and\u002For radiation or subjects who have undergone diagnostic biopsy for their original diagnosis and are deemed to be candidates for resection.\n* Subject age ≥ 18 years.\n* Adequate hematologic and end-organ function appropriate for surgery and panitumumab infusion as determined by routine preoperative evaluation or designee prior to infusion. If liver function, renal function, and hematologic laboratory test results are acceptable for elective surgery and panitumumab infusion, the patient is considered eligible for the study. Laboratory results will need to be obtained within 30 days prior to initiation of study treatment include:\n\n  1. Chemistry Panel - Potassium, BUN (or urea), and Creatinine\n  2. CBC with differential - WBC, including ANC, hemoglobin, hematocrit, and platelet count\n  3. Magnesium and Phosphorus\n* Women of childbearing potential must have a negative pregnancy test within 7 days of study drug administration.\n* Ability to understand and willingness to sign a written informed document or written informed consent via a surrogate consent rider from the patients' healthcare decision maker.\n\nExclusion Criteria:\n\n* Had a myocardial infarction, cerebrovascular accident, or uncontrolled chronic heart failure within 6 months prior to enrollment.\n* History of infusion reactions to any monoclonal antibody therapies.\n* Women who are currently pregnant or breastfeeding.\n* Participants presenting with a baseline QTcF interval \\> than 480 milliseconds.\n* Magnesium or phosphorus lower than normal institutional values, and subject is symptomatic.\n* Patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents.\n* Patients with a history or evidence of interstitial pneumonitis or pulmonary fibrosis.\n* Patients with severe renal disease or anuria",{"count":90,"type":21},30,[92],"EARLY_PHASE1","This pilot clinical study evaluates the safety and imaging performance of panitumumab-IRDye800 (pan800), a fluorescent, EGFR-targeted imaging agent - in patients undergoing neurosurgical resection of intracranial lesions.",[95,28,96,97,98],"Meningioma","Acoustic Neuroma","Brain Cancer","Pituitary Adenoma",[100,101,102,28,95,98,96,103,104],"Cancer","Malignant","Benign","Brain Masses","Intracranial Lesion","2026-06-26",{"date":73,"type":45},{"date":108,"type":21},"2026-07",{"date":110,"type":21},"2031-06",{"name":112,"class":52},"Eben Rosenthal",1,{"id":115,"slug":4,"hasResults":11,"nctId":116,"briefTitle":117,"officialTitle":118,"acronym":119,"eligibilityCriteria":120,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":121,"targetDuration":4,"studyType":22,"phases":123,"briefSummary":124,"conditions":125,"keywords":126,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":129,"lastUpdatePostDateStruct":130,"startDateStruct":132,"completionDateStruct":134,"leadSponsor":136,"locationsCount":113},"100614825","NCT07284628","Vortioxetine for Newly Diagnosed Glioblastoma","A Phase II Drug Repurposing Trial of Vortioxetine for the Treatment of Patients With Newly Diagnosed Glioblastoma","ReVoGlio","Inclusion Criteria:\n\n1. Male or female, age ≥18 years\n2. Patients with histologically confirmed newly diagnosed glioblastoma per CNS WHO 2021 classification\n3. O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status known or tissue available for testing\n4. Karnofsky performance status (KPS) ≥ 70%\n5. Intent to treat with standard radiochemotherapy per EANO guidelines (radiotherapy will 60 Gy in 1.8-2 Gy fractions. Concomitant chemotherapy with temozolomide (75 mg\u002Fm2 daily throughout radiotherapy, including at weekends) followed by six cycles of maintenance temozolomide (150-200 mg\u002Fm2, 5 out of 28 days). Short course radiotherapy at 40 Gy is not allowed.\n6. Female patients must be either documented not to be Women of Childbearing Potential (WOCBP) or must have a negative pregnancy test within 14 days of starting treatment. Additionally WOCBP must agree to use, from the screening to 6 months following the last study drug administration, highly effective contraception methods, as defined by the \"Recommendations for contraception and pregnancy testing in clinical trials\" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group (www.hma.eu\u002Fctfg.html) and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion or vasectomized partner. WOCBP are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).\n7. Male subjects able to father children must agree to use two acceptable methods of contraception throughout the study and during 6 months following the last study drug administration (e.g., condom with spermicidal gel). Double-barrier contraception is required.\n8. Personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.\n9. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.\n\nExclusion Criteria:\n\n1\\. Prior treatment for newly diagnosed glioblastoma except surgery. 2. Intent to be treated with tumor-treating fields. 3. Inability to undergo contrast-enhanced MRI. 4. Inadequate bone marrow, renal and hepatic function:\n\n* Absolute neutrophil count (ANC) \\\u003C 1.5 x 10.9\u002FL; platelets \\\u003C 100 x 10.9\u002FL\n* Hemoglobin (Hb) \\\u003C 9.0 g\u002Fdl. Blood marrow values must be measured independently of transfusion.\n* Chronically impaired renal function as indicated by creatinine clearance \\\u003C 50 mL\u002Fmin or serum creatinine \\> 1.5 upper limit of normal (ULN).\n* Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN) 9. Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol, in the opinion of the investigator.\n\n  10\\. Any contra-indication to vortioxetine. 11. Medically documented history of active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g., risk of doing harm to self or others), or patients with active severe personality disorders.\n\n  12\\. Pregnancy or breast feeding. 13. Presence of active and uncontrolled infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.\n\n  14\\. Concurrent malignancies unless the patient has been disease-free without intervention for at least one year.\n\n  15\\. Requirement of concurrent use of other anti-cancer treatments or agents other than study medication.",{"count":122,"type":21},78,[24],"There is a very urgent need to improve on the currently limited treatment options for patients with glioblastoma. Despite extensive knowledge on the molecular pathogenesis of glioblastoma obtained through genomic, transcriptional and proteomic profiling, targeted therapy efforts have not yielded major advances, likely because of interindividual and intraindividual tumor heterogeneity and redundant oncogenic pathway activation.\n\nAccordingly, there is a strong rationale to approach the challenge of glioblastoma from a different angle, e.g., by ex vivo drug sensitivity profiling which is agnostic to the molecular profile of a tumor. This approach that we have termed \"pharmacoscopy\", has previously been explored in liquid cancers and probably led to improved patient outcomes. Using pharmacoscopy, the antidepressant drug, vortioxetine, has been identified as a lead candidate for further exploration in patients with glioblastoma. Vortioxetine also demonstrated synergistic anti-glioma activity in combination with temozolomide or lomustine.\n\nThe ReVoGlio trial aims at demonstrating that vortioxetine, a drug selected based on ex vivo drug profiling (pharmacoscopy), is of benefit for patients with newly diagnosed glioblastoma.",[28],[28,127,128],"Drug repurposing","Vortioxetine","2026-06-25",{"date":131,"type":45},"2026-06-29",{"date":133,"type":45},"2026-06-24",{"date":135,"type":21},"2029-06",{"name":137,"class":52},"University of Zurich",{"id":139,"slug":4,"hasResults":11,"nctId":140,"briefTitle":141,"officialTitle":142,"acronym":4,"eligibilityCriteria":143,"healthyVolunteers":144,"sex":17,"minAge":145,"maxAge":146,"enrollmentInfo":147,"targetDuration":4,"studyType":22,"phases":149,"briefSummary":150,"conditions":151,"keywords":160,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":129,"lastUpdatePostDateStruct":163,"startDateStruct":164,"completionDateStruct":166,"leadSponsor":168,"locationsCount":170},"100541748","NCT06333899","Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion","A Pilot Study of Lorlatinib for Treatment of Children With Newly Diagnosed High-Grade Glioma With ROS-1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) or ALK (Anaplastic Lymphoma Kinase) Fusion","Inclusion Criteria:\n\n1. Patients must be ≥ 12 months and ≤ 21 years of age at the time of study enrollment on TarGeT-SCR.\n2. Diagnosis:\n\n   Patients with newly diagnosed high-grade glioma (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors harbor an ALK or ROS-1 fusion alteration are eligible. Patients must have had histologically verified high-grade glioma from diagnostic biopsy or resection. For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology consistent with diffuse WHO Grade 2-4. All other HGGs must be Grade 3 or 4.\n3. Disease Status:\n\n   Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e., no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented ALK or ROS-1 fusion, must be discussed with the Study Chair on a case-by-case basis.\n4. Performance Level:\n\n   Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n5. Prior Therapy:\n\n   * Patients must not have received any prior anti-cancer chemotherapy.\n   * Prior use of corticosteroids is allowed (see below Exclusion Criteria)\n6. Organ Function Requirements 6.1 Adequate Bone Marrow Function Defined as:\n\n   * Peripheral absolute neutrophil count (ANC) ≥ 1000\u002FμL\n   * Platelet count ≥ 100,000\u002FμL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)\n   * Hemoglobin \\>8 g\u002FdL (may receive transfusions) 6.2 Adequate Renal Function Defined as:\n   * Serum creatinine within normal institutional limits OR Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 6.3 Adequate Liver Function Defined as:\n   * Total bilirubin ≤ 2 × institutional upper limit of normal\n   * AST(aspartate aminotransferase)\u002FALT(alanine transaminase) ≤ 2.5 × institutional upper limit of normal 6.4 Adequate Pulmonary Function Defined as: Pulse oximetry \\> 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest).\n\n6.5Adequate Cardiac Function Defined as: QTc ≤ 470 msec (by Bazett formula) 6.6 Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.\n\n6.7 Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines\n\nExclusion Criteria:\n\n1. Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.\n\n   Females of reproductive potential must use an effective non-hormonal method of contraception, since lorlatinib can render hormonal contraceptives ineffective, during study treatment and for at least 6 months after the final dose. Males with female partners of reproductive potential must use effective contraception during treatment with lorlatinib and for 3 months after the final dose.\n2. Concomitant Medications\n\n   * Investigational Agents\u002FDrugs: Patients who have previously received or are currently receiving another investigational drug are not eligible.\n   * Anti-cancer Agents: Patients who have previously received or are currently receiving other anti-cancer agents, including chemotherapy, immunotherapy, monoclonal antibodies, biologic or targeted therapy, are not eligible\n3. Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.\n4. Patients who have received prior solid organ transplantation are not eligible.\n5. Patients must not have malabsorption syndrome or other condition affecting oral absorption.\n6. Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to treatment with loraltinib. Moderate inducers of CYP3A4 should be avoided\n7. Avoid concomitant use of lorlatinib with certain CYP3A substrates, for which minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.\n8. P-glycoprotein (P-gp) substrates: Lorlatinib is considered a moderate P-gp inducer. Co-administration of lorlatinib with P-gp substrates including but not limited to digoxin should be avoided as the concentration of these drugs may be reduced by lorlatinib.\n9. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.\n10. Patients with a known personal history of acute or chronic severe psychiatric disorders or current history of suicidal ideation and history of suicide attempt.",true,"1 Year","21 Years",{"count":148,"type":21},15,[92],"The goal of this study is to determine the response of the study drug loratinib in treating children who are newly diagnosed high-grade glioma with a fusion in ALK or ROS1. It will also evaluate the safety of lorlatinib when given with chemotherapy or after radiation therapy.",[152,153,154,155,28,156,157,158,159],"High Grade Glioma","Diffuse Intrinsic Pontine Glioma","Anaplastic Astrocytoma","Infant Type Hemispheric Glioma","Glioblastoma Multiforme","WHO Grade III Glioma","WHO Grade IV Glioma","Diffuse Midline Glioma, H3K27-altered",[161,162,152,153],"ALK fusion","ROS fusion",{"date":131,"type":45},{"date":165,"type":45},"2025-08-03",{"date":167,"type":21},"2035-06-01",{"name":169,"class":52},"Nationwide Children's Hospital",18,{"id":172,"slug":4,"hasResults":11,"nctId":173,"briefTitle":174,"officialTitle":175,"acronym":4,"eligibilityCriteria":176,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":177,"enrollmentInfo":178,"targetDuration":4,"studyType":22,"phases":180,"briefSummary":182,"conditions":183,"keywords":184,"overallStatus":188,"whyStopped":4,"lastUpdateSubmitDate":133,"lastUpdatePostDateStruct":189,"startDateStruct":190,"completionDateStruct":191,"leadSponsor":193,"locationsCount":4},"100645167","NCT07678138","Exploratory Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of Tumor Neoantigen-pulsed Autologous Dendritic Cell Injection (YS247, Beijing YSCell Biotech Co., Ltd. [Abbreviated as YS])in Patients With Recurrent or Progressive Glioblastoma","Exploratory Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of Tumor Neoantigen-pulsed Autologous Dendritic Cell Injection (YS247) in Patients With Recurrent or Progressive Glioblastoma","Inclusion Criteria:\n\n1. Age 18-75 years (inclusive), any gender.\n2. Histologically confirmed GBM (WHO Grade IV).\n3. Recurrence\u002Fprogression confirmed by MRI after standard therapy (surgery, Stupp protocol); ≥1 measurable lesion (max diameter ≥1.0 cm) on contrast-enhanced MRI per RANO criteria.\n4. KPS score ≥60, expected survival ≥6 months.\n5. ECOG score 0-2.\n6. Bridging therapy allowed during sample preparation; washout ≥7 days or 5 half-lives (whichever longer) before initial treatment.\n7. Radiotherapy completed ≥8 weeks before study drug initiation.\n8. Toxicity from prior anti-tumor therapy recovered to CTCAE V5.0 Grade 1 or below (except alopecia).\n9. Adequate organ function:\n\n   * ANC ≥1.5×10⁹\u002FL, ALC ≥0.8×10⁹\u002FL, HGB ≥90 g\u002FL, PLT ≥100×10⁹\u002FL\n   * AST\u002FALT ≤2.5×ULN, TBIL ≤2.5×ULN, ALB ≥3 g\u002FdL, ALP ≤2.5×ULN\n   * INR\u002FAPTT ≤1.5×ULN (except therapeutic anticoagulation)\n   * Cr ≤1.5×ULN or CrCl ≥60 mL\u002Fmin (Cockcroft-Gault)\n   * Normal ECG, LVEF ≥50% (ECHO)\n   * Resting SpO₂ \\>92% without oxygen\n10. Adequate venous access for PBMC collection, no contraindications.\n11. Sufficient tumor and blood samples for NGS via resection or biopsy.\n12. Negative serum pregnancy test (fertile females); effective contraception throughout screening, study, and 6 months after last dose for fertile participants\u002Fpartners.\n13. Compliance with study procedures and follow-up.\n14. Voluntary participation and signed informed consent.\n\nExclusion Criteria:\n\n1. Any other active malignancy.\n2. Participation in another clinical trial within 4 weeks before enrollment.\n3. Prior gene transfer therapy.\n4. Concurrent anti-tumor therapy within 4 weeks before initial treatment (except allowed bridging); blood transfusion, EPO, G-CSF, or GM-CSF within 14 days before PBMC apheresis.\n5. Live virus\u002Frecombinant vaccine within 4 weeks before first treatment; expected need for live attenuated vaccine within 6 months after last dose.\n6. Severe allergy or hypersensitivity.\n7. MRI contrast contraindications (pacemaker, pump, contrast allergy).\n8. Positive HIV, HBV, HCV, or TP.\n9. Primary\u002Fsecondary immunodeficiency or autoimmune disease (SLE, RA, IBD, autoimmune thyroid disease, autoimmune hepatitis, MS, vasculitis, glomerulonephritis, psoriasis, uncontrolled asthma).\n10. Severe infection within 1 month before treatment, uncontrolled infection, or antibiotics in the past week (except prophylaxis).\n11. Systemic immunosuppressive therapy within 30 days before initial treatment (short-term use allowed with sponsor approval; permitted: inhaled steroids, mineralocorticoids, low-dose steroids ≤10 mg\u002Fday prednisone equivalent).\n12. Uncontrolled systemic disease (NYHA III\u002FIV heart failure, unstable angina, MI, cirrhosis, renal failure, severe lung disease, hematological\u002Fgastrointestinal\u002Forgan failure, diabetes, uncontrolled hypertension).\n13. ICD-11 psychiatric\u002Fneurological disorders (epilepsy, schizophrenia, dementia, addiction) per investigator judgment.\n14. Clinically significant bleeding within 3 months or bleeding diathesis; arterial\u002Fvenous thromboembolism within 6 months (TIA, stroke, DVT, PE).\n15. Irreversible electrolyte imbalance.\n16. Anti-tumor therapy before apheresis: cytotoxic within 14 days; investigational within 28 days; immunomodulator within 7 days; targeted within 28 days.\n17. Pregnant or lactating female.\n18. Any other condition deemed unsuitable by the investigator.","75 Years",{"count":179,"type":21},9,[181],"NA","This is a single-center, open-label, dose-escalation, multiple-dose investigator-initiated trial (IIT). The trial aims to evaluate the safety and tolerability of autologous dendritic cell injection sensitized with tumor neoantigens (YS247) in participants with recurrent or progressive glioblastoma, as well as to assess preliminary efficacy and pharmacodynamic characteristics. The study consists of four phases: screening, baseline, treatment, and follow-up. During the treatment phase, participants will be assigned to three dose groups (low, medium, and high) and enrolled following the \"3+3\" dose-escalation principle. YS247 will be administered subcutaneously once every 2 weeks for a total of 8 consecutive doses.",[28],[28,185,186,187],"Immune cell therapy","Dendritic cell (DC)","Tumor neoantigen","NOT_YET_RECRUITING",{"date":75,"type":45},{"date":73,"type":21},{"date":192,"type":21},"2028-05-30",{"name":194,"class":52},"Huanhu Hospital Affiliated to Tianjin Medical University",{"id":196,"slug":4,"hasResults":11,"nctId":197,"briefTitle":198,"officialTitle":199,"acronym":4,"eligibilityCriteria":200,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":201,"targetDuration":4,"studyType":22,"phases":203,"briefSummary":204,"conditions":205,"keywords":207,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":133,"lastUpdatePostDateStruct":209,"startDateStruct":210,"completionDateStruct":212,"leadSponsor":214,"locationsCount":113},"100593215","NCT07003542","A Phase 2 and Pharmacodynamic Study of Sitagliptin in Patients With Progressive Grade 4 Gliomas","Targeting Macrophage Migration Inhibitory Factor: A Phase 2 and Pharmacodynamic Study of Sitagliptin in Patients With Progressive Grade 4 Gliomas","Inclusion Criteria:\n\n1. Participants must have histologically or cytologically confirmed WHO grade 4 glioma (including tumors with molecularly defined grade 4 astrocytoma) for whom a clinically-indicated tumor resection is planned.\n2. Participants must not have received sitagliptin or other gliptins.\n3. Participants must, in the opinion of the investigator be able to tolerate a pre-operative dexamethasone dose of 4 mg\u002Fd or the equivalent dose of an alternate glucocorticoid.\n4. Age \\>18 years\n5. Karnofsky performance status ≥ 60%\n6. Participants must have adequate organ function and laboratory parameters within 21 days of study entry as defined below:\n\n   * Hemoglobin ≥ 9 g\u002Fdl\n   * Absolute neutrophil count ≥ 1,500\u002FmcL\n   * Platelet count ≥ 100,000\u002FmcL\n   * Total bilirubin \\\u003C 1.5x institutional upper limit of normal (ULN)\n   * AST (SGOT) ≤ 3x institutional ULN\n   * ALT (SGPT) ≤ 3x institutional ULN\n   * Calculated creatinine clearance \\> 50 mL\u002Fmin or creatinine \\\u003C 1.5x institutional upper limit of normal (ULN)\n   * Prothrombin time\u002Finternational normalized ratio (PT\u002FINR) \\\u003C 1.4 for participants not on warfarin.\n7. Participants on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:\n\n   * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)\n   * In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin.\n8. Women of childbearing potential must have a negative pregnancy test within 21 days of study entry. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while taking part in this study, she should inform her treating physician immediately. Men of reproductive potential treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug.\n9. Participants must be able to swallow whole tablets.\n10. Participants must have the following minimum intervals from prior treatments:\n\n    * surgery - 4 weeks\n    * nitrosoureas - 6 weeks\n    * cytotoxic chemotherapy - standard intervals depending on the most recent regimen. E.g., for temozolomide 23 days after most recent dose.\n    * For drugs not listed, the research nurse, treating investigator, and principal investigator will decide on the appropriate interval.\n    * Investigational therapy or non-cytotoxic therapy - 2 weeks.\n    * For bevacizumab - 4 weeks from expected date of protocol surgery\n11. Participants positive for human immunodeficiency virus (HIV) are allowed on study (note: HIV testing is not required), but HIV-positive participants must have:\n\n    * An undetectable viral load within 6 months of registration.\n    * A stable regimen of highly active anti-retroviral therapy (HAART)\n    * No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections\n12. For participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load Note: Known positive test for HCV ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy.\n13. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n\n    Note: A known positive test for HBV surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Participants who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g., participants immunized against hepatitis B)\n14. Patient must be deemed by investigator to be a candidate for post-operative chemotherapy.\n15. Participants must have the ability to understand and the willingness to sign a written informed consent document.\n\n    Exclusion Criteria:\n16. Prior treatment toxicities not resolved to ≤ Grade 1 according to NCI CTCAE Version 5.0 except alopecia and neuropathy.\n17. Participants receiving any other investigational agents.\n18. History of allergic reactions attributed to compounds of similar chemical or biologic composition to sitagliptin.\n19. Participants with uncontrolled diabetes mellitus\n20. Participants who require insulin therapy or a sulfonylurea\n21. Participants with documented history of hypoglycemia requiring medical intervention or who in the opinion of the investigator are not suitable to receive sitagliptin.\n22. Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n23. Other prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are excluded. Otherwise, participants with prior or concurrent malignancy are eligible.\n24. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 diarrhea of any etiology at screening) (National Cancer Institute \\[NCI\\] Common Terminology Criteria for Adverse Events Version 5.0 \\[CTCAE v.5.0\\]).\n25. Pregnant or breastfeeding.\n26. Unable or unwilling to swallow tablets.\n27. Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness\u002Fsocial situations that would, in the investigator's judgment, make the patient inappropriate for this study.",{"count":202,"type":21},48,[24],"The purpose of this study is to evaluate whether treating glioblastoma patients with sitagliptin can improve immune response against the tumor by targeting specific immune cells called myeloid-derived suppressor cells (MDSCs) that suppress your body's natural immune response against cancer.\n\nSitagliptin is an investigational drug for this condition that works by inhibiting an enzyme called dipeptidyl peptidase 4 (DPP-4), which MDSCs rely on to enter the brain and function. While sitagliptin is FDA-approved for diabetes treatment, its use in glioblastoma is investigational (experimental).",[28,206],"Brain Tumor",[208],"Myeloid-derived suppressor cells",{"date":129,"type":45},{"date":211,"type":45},"2026-03-16",{"date":213,"type":21},"2028-06",{"name":215,"class":52},"Case Comprehensive Cancer Center",{"id":217,"slug":4,"hasResults":11,"nctId":218,"briefTitle":219,"officialTitle":220,"acronym":4,"eligibilityCriteria":221,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":222,"targetDuration":4,"studyType":22,"phases":224,"briefSummary":226,"conditions":227,"keywords":228,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":133,"lastUpdatePostDateStruct":231,"startDateStruct":232,"completionDateStruct":234,"leadSponsor":236,"locationsCount":113},"100482675","NCT05565118","Prospective Surgical Study on the Pattern of Electrical Activity in High Grade Glioma as a Predictor of Progression","Prospective Surgical Study on the Pattern of Electrical Activity in High Grade Glioma (WHO Grade III and IV) as a Predictor of Progression","Inclusion Criteria:\n\n* Participants who have the appearance of high-grade glioma (HGG, WHO Grade 3 and 4, including GBM) on MR imaging are allowed to consent and will undergo the procedure if the frozen is consistent with HGG\n\nOR\n\n* Participants with a history of histologically-confirmed diagnosis of high- grade glioma that are undergoing resection of a recurrent\u002Fprogressive tumor that is likely recurrent\u002Fprogressive high- grade glioma as identified on preoperative MR imaging\n* Age ≥ 18 years old\n* Volumetric MRI within 1 month prior to surgery\n* Karnofsky performance status of 60 or higher\n* The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.\n* Participants must be considered appropriate neurosurgical candidates with the following screening\u002Fbaseline laboratory values within 1 month prior to surgery:\n\n  * Absolute neutrophil count ≥ 1500\u002FµL\n  * Platelets ≥ 100 000\u002FµL\n  * International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × Upper limit of normal (ULN) unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants\n  * Urine or Serum Pregnancy Test = Negative (Not applicable to participants with bilateral oophorectomy and\u002For hysterectomy or to those participants who are postmenopausal).\n\nExclusion Criteria:\n\n* Severe co-morbidity that would confer excess risk of surgery as determined by the treating physician.\n* Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.\n* Is pregnant\n* Coagulopathy or platelet dysfunction that increases the risk of intra and postoperative hemorrhage\n* Tumor location requiring DE placement\u002Fbiopsy in eloquent or critical region of the brain (e.g. primary motor and sensory cortices, speech and vision centers, thalamus, basal ganglia, cerebellum, brain stem) as deemed by the neurosurgeon designing the surgical plan",{"count":223,"type":21},10,[225],"PHASE1","The purpose of this study is to test the safety and feasibility of recording brain activity within and around high-grade glioma tumors at the time of surgery. A small biopsy will be taken at the sites of the recordings.",[152,28],[152,28,229,230],"Neural Recording","Electrical Activity",{"date":129,"type":45},{"date":233,"type":45},"2024-04-09",{"date":235,"type":21},"2026-12",{"name":215,"class":52},{"id":238,"slug":4,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":239,"targetDuration":4,"studyType":22,"phases":240,"briefSummary":26,"conditions":241,"keywords":242,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":133,"lastUpdatePostDateStruct":243,"startDateStruct":244,"completionDateStruct":245,"leadSponsor":246,"locationsCount":53},"100360233",{"count":20,"type":21},[24,25],[28],[28,30,31,32,33,34,35,36,37,38,39,40],{"date":105,"type":45},{"date":47,"type":45},{"date":49,"type":21},{"name":51,"class":52},{"id":248,"slug":4,"hasResults":11,"nctId":249,"briefTitle":250,"officialTitle":251,"acronym":4,"eligibilityCriteria":252,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":253,"targetDuration":4,"studyType":22,"phases":255,"briefSummary":256,"conditions":257,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":258,"lastUpdatePostDateStruct":259,"startDateStruct":260,"completionDateStruct":262,"leadSponsor":264,"locationsCount":113},"100644033","NCT07670026","Intensified Adjuvant Therapy for High-Risk Newly Diagnosed Glioblastoma With Subtotal Resection or Short-Term Progression","Intensified Adjuvant Therapy for High-Risk Newly Diagnosed Glioblastoma With Subtotal Resection or Short-Term Progression: A Prospective, Single-Arm Phase II Clinical Study","Inclusion Criteria:\n\n* Voluntary participation in the clinical study: fully understands and is informed about the study and has signed the informed consent form in writing; willing to comply with and able to complete all trial procedures.\n* Age: \\>=18 years; male or female.\n* Pathologically confirmed Glioblastoma.\n* Subtotal resection or recurrent\u002Fprogressive disease 4-6 weeks after surgery (before radiotherapy).\n* Adequate organ and bone marrow function, with no severe hematopoietic dysfunction or cardiac, pulmonary, hepatic, renal dysfunction, or immunodeficiency:\n\n  1. Complete blood count: absolute neutrophil count (ANC) \\>=1.5\\*10\\^9\u002FL (1500\u002Fmm3), platelets \\>=75\\*10\\^9\u002FL, hemoglobin \\>=9 g\u002FdL (if there is bone marrow involvement, platelets \\>=50\\*10\\^9\u002FL, ANC \\>=1.0\\*10\\^9\u002FL, hemoglobin \\>=8 g\u002FdL).\n  2. Liver function: serum bilirubin \\\u003C=1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \\\u003C=1.5 times ULN (if there is liver involvement, AST and ALT \\\u003C=5 times ULN are allowed).\n  3. Renal function: serum creatinine \\\u003C=1.5 times ULN.\n  4. Coagulation function: INR \\\u003C=1.5 times ULN; PT and APTT \\\u003C=1.5 times ULN (unless the subject is receiving anticoagulant therapy and PT and APTT at screening are within the expected range for anticoagulant therapy).\n* Left ventricular ejection fraction (LVEF) \\>=50% on cardiac function examination.\n* Negative serum pregnancy test, and effective contraceptive measures from signing the informed consent form until 6 months after the last chemotherapy.\n* Thyroid-stimulating hormone (TSH), free thyroxine (FT4), or free triiodothyronine (FT3) within the normal range ±10%.\n* Ophthalmologic examination: including dilated fundus examination, slit-lamp examination, and color fundus photography.\n\nExclusion Criteria:\n\n* Currently participating in another clinical study, or less than 4 weeks since completion of treatment in a previous clinical study.\n* History of malignancy other than Glioblastoma within the past 3 years, or another uncured primary malignancy.\n* Prior history of brain radiotherapy.\n* Pregnant or lactating women.\n* Patients assessed as having contraindications to radiotherapy.\n* Severe active comorbidity that would affect the study treatment.\n* Active infection requiring systemic anti-infective treatment, including but not limited to bacterial, fungal, or viral infection.\n* Within 6 months before screening, New York Heart Association (NYHA) class III or IV heart failure, unstable angina, severe poorly controlled ventricular arrhythmia, or electrocardiographic evidence of acute ischemia or myocardial infarction.\n* QTcF interval \\>480 msec, unless secondary to bundle branch block.\n* Uncontrolled concomitant disease, including but not limited to uncontrolled hypertension, active peptic ulcer disease, or hemorrhagic disease.\n* Prior history of mental illness; lack of capacity for civil conduct or limited capacity for civil conduct.\n* Any medical history or disease evidence, treatment, or abnormal laboratory value that may interfere with trial results or prevent the subject from fully participating in the study, or any other condition that the investigator considers unsuitable for enrollment.",{"count":254,"type":21},31,[24],"\\*\\*Brief Summary\\*\\*\n\nThe goal of this clinical trial is to learn whether intensified adjuvant treatment is safe and may help delay disease progression in adults with high-risk newly diagnosed glioblastoma. High-risk newly diagnosed glioblastoma in this study includes glioblastoma that has been partially removed by surgery or glioblastoma that shows early progression or recurrence before postoperative radiotherapy.\n\nThe main questions this study aims to answer are:\n\n* Does intensified adjuvant treatment improve median progression-free survival in participants with high-risk newly diagnosed glioblastoma?\n* How long do participants survive after receiving this treatment?\n* What medical problems do participants have during or after intensified adjuvant treatment?\n* How often do participants develop radiation necrosis?\n* How does this treatment affect participants' quality of life?\n\nParticipants will:\n\n* Receive postoperative concurrent radiotherapy and temozolomide chemotherapy.\n* Receive a higher radiation dose to the residual tumor or early recurrent\u002Fprogressive lesion, while standard radiation doses are given to the tumor bed and surrounding high-risk and low-risk areas.\n* Receive adjuvant temozolomide after concurrent chemoradiotherapy.\n* Receive sintilimab and bevacizumab by intravenous infusion once every 21 days for up to 1 year.\n* Have regular blood tests, biochemical tests, thyroid function tests, myocardial enzyme tests, electrocardiograms, and other safety assessments.\n* Have enhanced brain MRI scans regularly to evaluate disease status.\n* Be followed by clinic visits and\u002For telephone calls to collect information about disease progression, survival, side effects, later cancer treatments, and quality of life.",[28],"2026-06-22",{"date":129,"type":45},{"date":261,"type":45},"2025-12-01",{"date":263,"type":21},"2027-12-01",{"name":265,"class":52},"Second Affiliated Hospital, School of Medicine, Zhejiang University",{"id":267,"slug":4,"hasResults":11,"nctId":268,"briefTitle":269,"officialTitle":270,"acronym":4,"eligibilityCriteria":271,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":272,"targetDuration":4,"studyType":22,"phases":274,"briefSummary":275,"conditions":276,"keywords":282,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":258,"lastUpdatePostDateStruct":291,"startDateStruct":293,"completionDateStruct":295,"leadSponsor":297,"locationsCount":299},"100414594","NCT04678648","A Trial of RSC-1255 for Treatment of Patients With Advanced Malignancies","A Phase Ia\u002FIb, Open Label, Multi-center, Non-randomized Dose Escalation and Dose Expansion Study of RSC-1255 Alone or in Combination With Hydroxychloroquine in Patients With Advanced Solid Tumor Malignancies","Inclusion Criteria (Key Factors):\n\n1. Has pathologically confirmed advanced or metastatic malignancy characterized by one or more of the following:\n\n   * Participant is intolerant of existing therapy(ies) known to provide clinical benefit for their condition\n   * Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit\n   * Malignancy has progressed on standard therapy\n2. Has evaluable or measurable tumor(s) in dose-escalation by standard radiological and\u002For laboratory assessments as applicable to their malignancy.\n3. Has adequate performance status (PS): Eastern Co-operative Oncology Group (ECOG).\n4. Is age ≥ 18 years.\n5. Has either tissue agnostic tumors and documented RAS mutations or with glioblastoma with or without mutation in RAS\n\nExclusion Criteria (Key Factors):\n\n1. Participants receiving cancer therapy at the time of enrollment.\n2. Any clinically significant disease or condition affecting a major organ system.\n3. Significant cardiovascular disease or electrocardiogram (ECG) abnormalities.\n4. Known Gilbert's disease.\n5. Has had a previous (within 2 years) or has a current malignancy other than the target cancer.\n6. Intermittent hypokalemia\n7. Grade 1 or higher nausea, vomiting, diarrhea at baseline due to underlying disease",{"count":273,"type":21},134,[225],"RSC-101 is a Phase 1a\u002F1b clinical trial of RSC-1255 in adult study participants with advanced solid tumor malignancies who are intolerant of existing therapies known to provide clinical benefit, have disease that has progressed after standard therapy, or have previously failed other therapies. The study has two phases. The purpose of Phase 1a (Dose Escalation) is to confirm the appropriate treatment dose and Phase 1b (Dose Expansion) is to characterize the safety and efficacy of RSC-1255.",[277,278,279,280,28,281],"Advanced Malignant Solid Neoplasm","RAS Mutation","Lung Cancer","Colon Cancer","Pancreatic Cancer",[283,100,284,285,286,287,28,288,289,290],"Malignancy","Refractory","RAS mutation","Lung","Colon","RSC-1255","Progression","Pancreatic",{"date":292,"type":45},"2026-06-23",{"date":294,"type":45},"2021-03-03",{"date":296,"type":21},"2027-01-30",{"name":298,"class":82},"RasCal Therapeutics, Inc.",3,{"id":301,"slug":4,"hasResults":11,"nctId":302,"briefTitle":303,"officialTitle":304,"acronym":4,"eligibilityCriteria":305,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":306,"targetDuration":4,"studyType":22,"phases":308,"briefSummary":309,"conditions":310,"keywords":313,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":315,"lastUpdatePostDateStruct":316,"startDateStruct":317,"completionDateStruct":319,"leadSponsor":321,"locationsCount":113},"100643886","NCT07668869","TTFields Plus FET-PET-Guided Stereotactic Radiosurgery Versus TTFields Alone for Recurrent Glioblastoma (Tarrget 2.0)","Tumor Treating Fields (TTFields) Concomitant With Stereotactic Radiosurgery Based on FET-PET vs TTFields Alone for the Treatment of Recurrent, Glioblastoma (Tarrget 2.0)","Inclusion Criteria:\n\n* Age ≥18 years\n* Karnofsky Performance Status ≥70\n* Histologically confirmed IDH-wildtype glioblastoma\n* First, second, or third recurrence\n* Radiological recurrence according to RANO 2.0 criteria\n* Prior radiotherapy and temozolomide treatment\n* At least 6 months since completion of previous radiotherapy\n* Contrast-enhancing recurrent lesion visible on MRI\n* Maximum recurrent lesion diameter ≤5 cm\n* Available molecular profile including IDH and MGMT status\n* Adequate hematologic, renal, and hepatic function\n* Written informed consent\n\nExclusion Criteria:\n\n* Previous bevacizumab treatment\n* Planned chemotherapy or targeted therapy after study intervention\n* Previous stereotactic re-irradiation within the planned treatment field\n* More than three recurrences\n* Significant psychiatric disorders\n* Significant unrelated neurological disease\n* Implanted pacemaker, defibrillator, deep brain stimulator, or other incompatible electronic device\n* Pregnancy or breastfeeding\n* Active intracranial hemorrhage\n* Uncontrolled hypertension\n* Severe renal dysfunction\n* Participation in another interventional study likely to interfere with this study",{"count":307,"type":21},92,[181],"This study evaluates whether the addition of FET-PET-guided stereotactic radiosurgery (SRS) to Tumor Treating Fields (TTFields) improves survival outcomes in patients with recurrent IDH-wildtype glioblastoma.\n\nPatients with recurrent glioblastoma have limited treatment options and poor prognosis. TTFields is a non-invasive antimitotic therapy that has demonstrated efficacy in recurrent glioblastoma. Stereotactic radiosurgery is commonly used in selected patients with recurrent disease; however, treatment efficacy may be limited by the infiltrative nature of glioblastoma and challenges in accurate target delineation.\n\nThe study hypothesizes that combining TTFields with FET-PET-guided stereotactic radiosurgery will improve one-year overall survival compared with TTFields alone. Participants will be randomized in a 1:1 ratio to receive either TTFields plus stereotactic radiosurgery or TTFields alone.",[28,311,312],"Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype","Glioblastoma Multiforme, Adult",[314],"glioblastoma, TTF, SRS, radiosurgery, stereotactic radiotherapy","2026-06-19",{"date":129,"type":45},{"date":318,"type":45},"2025-12-30",{"date":320,"type":21},"2032-06",{"name":322,"class":52},"Prof. Franciszek Lukaszczyk Memorial Oncology Center",{"id":324,"slug":4,"hasResults":11,"nctId":325,"briefTitle":326,"officialTitle":327,"acronym":4,"eligibilityCriteria":328,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":329,"enrollmentInfo":330,"targetDuration":4,"studyType":22,"phases":332,"briefSummary":333,"conditions":334,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":315,"lastUpdatePostDateStruct":335,"startDateStruct":336,"completionDateStruct":338,"leadSponsor":340,"locationsCount":223},"100610287","NCT07225621","Adjuvant Temozolomide ± 5-Aminolevulinic Acid + Low Intensity Diffuse Ultrasound Sonodynamic Therapy System for Newly Diagnosed Glioblastoma","Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial Comparing Standard of Care Adjuvant Temozolomide With or Without 5-Aminolevulinic Acid (5-ALA) With Concomitant Low Intensity Diffuse Ultrasound (LIDU) Sonodynamic Therapy (SDT) System In Patients With Newly Diagnosed Glioblastoma After Completion of Chemoradiotherapy","Inclusion Criteria:\n\n1. Patient must provide informed consent, stating understanding of the procedures and investigational nature of the study treatment, and willingness to comply with study requirements\n2. ≥ 18 and ≤ 80 years of age\n3. WHO performance status of ≤ 2 at screening\n4. Newly diagnosed Histologically proven glioblastoma (WHO criteria 2021), absence of IDH mutation demonstrated by negative IDH1 R132H staining on Immunohistochemistry.\n5. GBM patients that have an absence of disease progression post craniotomy and TMZ\u002FRT. Note: patients must have undergone prior tumor resection to the extent safely feasible (biopsy only are not eligible).\n6. Completion of chemoradiation consisting of radiotherapy (30 x 20 Gy, or equivalent regimen, eg 33 x 18 Gy), with ≥ 90% of the planned radiation therapy dose delivered and concomitant TMZ chemotherapy (75 mg\u002Fm2), \\>66% of the planned doses administered.\n7. Any toxicity attributable to recently completed chemoradiation must be resolved to the patient's baseline level or ≤ Grade 2 (except alopecia or lymphopenia).\n8. Adequate bone marrow and organ function, defined by the following laboratory values: A. Absolute neutrophil count (ANC) ≥ 1000 cells\u002Fmm3 B. Platelet count ≥ 50,000 cells\u002Fmm3 C. Hemoglobin (Hgb) ≥ 8 g\u002Fdl D. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x upper limit of normal (ULN) E. Total bilirubin ≤ 3 x ULN (unless gilbert's syndrome, then patients may be eligible if total serum bilirubin is ≤ 5.0 x ULN or direct bilirubin is ≤ 3 x ULN) F. Creatinine clearance (CrCl) as estimated by Cockcroft-Gault equation of ≥ 50 ml\u002Fmin\n9. Adequate coagulation function defined as PT (prothrombin time)\u002FPTT (partial thromboplastin time) defined as either results within normal institutional values or not considered clinically significant \\\u003C1.5 x ULN.\n10. Non-pregnant, non-lactating females who are postmenopausal, surgically sterile (bilateral tubal ligation with surgery at least 6 weeks prior to study initiation or hysterectomy), or who agree to use effective contraceptive methods as defined by the protocol during the study and for 30 days after the last investigational treatment, see Appendix 1. Postmenopausal is defined as at least 12 months natural spontaneous amenorrhea and a serum follicle stimulating hormone (FSH) concentration ≥ 40 IU\u002FL, or at least 6 weeks following surgical menopause (bilateral oophorectomy). See Appendix 1, females on HRT and whose menopausal status is in doubt will be required to use one of the non-estrogen hormonal highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study enrollment.\n11. Women of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test within 7 days prior to first 5-ALA administration\n12. Male patients must be surgically sterile (i.e., 3 months post- vasectomy) or willing to use a highly effective double-barrier contraception method (e.g., male condom with diaphragm or male condom with cervical cap) for the duration of the study and for at least 30 days following SDT treatment. Male patients must not donate sperm from the time of study drug dosing until 30 days following SDT treatment.\n13. No anti-cancer treatment during adjuvant setting after completion of radiation therapy with anything other than temozolomide on Day 2 (+\u002F-1 day) for 5 days per the approved Package Insert (PI).\n\nExclusion Criteria:\n\n1. Any component of the tumor in the infratentorial location (cerebellar or brainstem tumors are excluded)\n2. Bihemispheric disease or tumors that involve the bilateral corpus callosum, or disease burden involving the brain stem or cerebellum based on MRI post-gadolinium enhancement,\n3. Multi- centric disease (enhancing or non-enhancing) or multi-focal disease (defined as 2 separate areas of contrast enhancement measuring at least 1 cm that are not contiguous and cannot be encompassed in sonication field on either fluid-attenuated inversion recovery (FLAIR) or T2 hyperintensity.\n4. Leptomeningeal disease\n5. 6\\. A diagnosis of glioscarcoma by histopathology Intent to undergo treatment with the tumor treating fields (TTF) at any time during the study, use prior to screening is permitted.\n\n7\\. Corticosteroid use \\> 4 mg\u002Fday of dexamethasone (or equivalent), steroid dose should be stable or decreasing for ≥1 week prior to randomization 8. Inability to undergo MRI or receive gadolinium (Gd)-based contrast agents 9. Hypersensitivity to 5-ALA or porphyrins 10. Patient head size \\> 16.6 cm in breadth (max width of head, above the ears) and \\> 21.3 cm in length (front to back) to ensure fit within the helmet transducer array. 11. Skull voids\u002Fdefects \\> 10 mm diameter if defect is open, or \\> 14 mm if defect is covered with titanium burr hole cover, titanium mesh, or similar repair hardware. Note, Longeviti Neuro Solutions or other sonolucent implants should be treated as open defects and therefore may not exceed 10 mm in diameter. 12. Hemorrhagic or ischemic stroke (including transient ischemic attacks) and central nervous system bleeding in the preceding 6 months that are not related to glioma surgery. History of prior intratumoral bleeding prior to screening is not an exclusion criterion; however, patients with a history of prior intratumoral or intracranial bleeding will undergo a non-contrast head CT to exclude acute bleeding. 13. Has any history of glioma, a concurrent malignancy, or malignancy within 3 years of randomization, unless definitive therapy is completed, with the exception of basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast that has completed curative therapy 14. Patients who have clinically significant cerebral edema requiring urgent intervention (e.g., surgery, initiation of steroids, escalating doses of steroids). 15. Patients with rapid clinical deterioration that, in the opinion of the investigator, is likely to worsen during the first cycle of treatment. 16. Any prior treatment for glioma, aside from surgical resection, and chemoradiation with TMZ. TTF is permitted prior to study entry. Agents used for diagnosis, imaging or visualization, even if investigational, are not exclusionary. Exclusionary treatments would include, but are not limited to: A. Stereotactic radiosurgery B. Placement of Gliadel® (carmustine; BCNU) wafers C. Any other intratumoral or intracavity treatment, D. Receipt of other chemotherapies, bevacizumab, immunotherapy (including vaccine) or investigational agents. 17. Acute or chronic types of porphyria. 18. Gastrointestinal disorder that negatively affects absorption. 19. Known active hepatitis B or C (Note: testing is not required). 20. Known human immunodeficiency virus (HIV) infection (Note: testing is not required). 21. Participation in another interventional clinical trial for GBM. (Observational studies are allowable) 22. Unable to avoid phototoxic drugs (e.g., St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, quinolones, and tetracyclines) for 24 hours prior to and following 5- ALA administration. 23. Any other concurrent severe or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, cardiac disease, clinically significant psychiatric or neurological disorder, active or uncontrolled infection). 24. Women who are pregnant or breastfeeding 25. Patients with a condition the Investigator believes would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results or put the patient at undue risk.","80 Years",{"count":331,"type":21},103,[24],"The purpose of this research is to test an investigational device using ultrasound along with an investigational drug to see if it is useful in treating glioblastoma following standard of care therapy surgery and chemoradiation. This study is evaluating an experimental treatment for glioblastoma that uses an investigational drug (5-ALA) combined with a non-invasive ultrasound device (LIDU) to target tumor cells. Patients meeting the entry requirements to be in the study, will be equally randomly assigned to receive the study device plus the active study drug plus active ultrasound, or to a \"sham\" procedure where the ultrasound is not being activated and the study drug is a placebo (looks the same but does not contain active drug). Neither the patient or the investigator will know who is in the active group or not. Both groups will continue to receive the standard therapy of oral Temozolomide.",[28,67],{"date":292,"type":45},{"date":337,"type":45},"2026-01-28",{"date":339,"type":21},"2028-12",{"name":341,"class":82},"Alpheus Medical, Inc.",{"id":343,"slug":4,"hasResults":11,"nctId":344,"briefTitle":345,"officialTitle":346,"acronym":347,"eligibilityCriteria":348,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":177,"enrollmentInfo":349,"targetDuration":4,"studyType":22,"phases":351,"briefSummary":352,"conditions":353,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":315,"lastUpdatePostDateStruct":354,"startDateStruct":355,"completionDateStruct":357,"leadSponsor":359,"locationsCount":113},"100484641","NCT05590689","Radiodynamic Therapy (RDT) With Gliolan in Patients With First Recurrence of Brain Tumor","Phase I\u002FII Dose Escalation Trial of Radiodynamic Therapy (RDT) With 5-Aminolevulinic Acid in Patients With First Recurrence of Glioblastoma","ALA-RDTinGBM","Inclusion Criteria:\n\n* Written patient consent after comprehensive information\n* Age \\>\u002F= 18 years\n* Recurrence of supratentorial glioblastoma after initial resection and adjuvant therapy (e.g. radio-chemotherapy, targeted therapies, antiangiogenic therapies as determined by the tumor board) (with planned second resection cohort 0 and 1), second or third recurrences permitted\n* Clinically indicated further radiotherapy as per decision of the tumor board as part of therapy for recurrence\n* Histological verification of recurrent glioblastoma independent of methylated MGMT promotor status when alkylating chemotherapy failed at this time.\n* Karnofsky Performance Score ≥ 60\n* For female and male patients and their female partners of childbearing\u002Freproductive potential(\\*): Willingness to apply highly effective contraception (Pearl index \\\u003C1) during the entire study (and for at least 6 months after the first application of 5-ALA). Such methods include:\n\n  1. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: I. oral II. intravaginal III. transdermal\n  2. progestogen only hormonal contraception associated with inhibition of ovulation: I. oral II. injectable III. implantable\n  3. intrauterine device (IUD)\n  4. intrauterine hormone-releasing system (IUS)\n  5. bilateral tubal occlusion\n  6. vasectomised partner\n  7. male patients have to use a condom\n  8. sexual abstinence\n* Pre-menopausal(\\*) female patients with childbearing potential: a negative pregnancy test must be obtained max. 72h prior to treatment start\n* Adequate liver function: bilirubin \\\u003C 1.5 times above upper limit of normal range (ULN), alanine transaminase (ALT\u002FSGPT) and aspartate transaminase (AST\u002FSGOT) \\\u003C 3 times ULN. In the case of documented or suspected Gilbert's disease bilirubin \\\u003C 3 times ULN.\n* Adequate renal function: creatinine \\\u003C 3 times above ULN; eGFR \\>\u002F= 60 ml\u002Fmin, Blood clotting: INR\u002FQuick\u002FPT and PTT within acceptable limits according to the investigator.\n\n(\\*) Definition: A man is considered of reproductive potential after puberty unless permanently sterile by bilateral orchidectomy. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A post-menopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.\n\nExclusion Criteria:\n\n* Patient unable to undergo imaging by MRI, PET or contrast-enhanced CT for whatever reason (e.g. pace-maker)\n* Pregnant and breastfeeding women\n* Past medical history of diseases with poor prognosis, e.g., severe coronary heart disease, heart failure (NYHA III\u002FIV), severe and poorly controlled diabetes, immune deficiency, residual deficits after stroke, severe mental retardation or other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)\n* Any active infection (at the discretion of the investigator)\n* Hypersensitivity against porphyrins\n* Known diagnosis of porphyria\n* Participation in another clinical trial with therapeutic intervention or use of any other therapeutic interventional agent other than the standard therapy since diagnosis of glioblastoma\n* Known intolerance to study medication\n* Pre-treatment with other potentially phototoxic or photosensitizing substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts, products containing St. John's wort ) during the 2 weeks preceding RDT",{"count":350,"type":21},34,[225,24],"The investigational drug 5-ALA (known under the trade name Gliolan®) is an approved drug for the surgical removal of malignant glioma (WHO grade III and IV). In this trial, the drug is being tested outside of its actual approval as a radiosensitizer in combination with conventional radiotherapy for first-time recurrence (relapse) of malignant glioma. In this clinical trial, the investigational drug 5-ALA is being used for the first time in a multiple dose escalation regimen in combination with radiotherapy following surgical removal of a recurrent malignant glioma in humans. The investigational drug, 5-ALA, has been used as a single dose to date as a standard of care for visualization of malignant tissue in the surgical removal of gliomas.\n\nThe planned clinical trial will first and foremost investigate how well repeated administration of the investigational drug 5-ALA is tolerated in combination with radiotherapy. At the same time, the design of the trial serves to optimize this novel therapeutic procedure with regard to the frequency of administration of the investigational drug 5-ALA in combination with radiotherapy for future clinical trials.\n\nAs a secondary objective, the efficacy of additional 5-ALA administration will also be investigated.",[28],{"date":292,"type":45},{"date":356,"type":45},"2022-11-09",{"date":358,"type":21},"2028-01",{"name":360,"class":52},"Universität Münster",{"id":362,"slug":4,"hasResults":11,"nctId":363,"briefTitle":364,"officialTitle":364,"acronym":4,"eligibilityCriteria":365,"healthyVolunteers":144,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":366,"targetDuration":4,"studyType":368,"phases":4,"briefSummary":369,"conditions":370,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":375,"lastUpdatePostDateStruct":376,"startDateStruct":377,"completionDateStruct":379,"leadSponsor":381,"locationsCount":113},"100644107","NCT07664579","Investigating the Feasibility and Acceptability of an Innovative Interdisciplinary Supportive Care Program: Couples Coping Together Against Cancer","Inclusion Criteria:\n\n* Have received a diagnosis of a primary brain tumor (glioblastoma), or other cancers (breast, lung, etc.)\n* Are new patients to City of Hope (COH) (all sites) or receive at least some of their care at City of Hope- Duarte Campus (care is defined as: procedures, consults, laboratories, imaging, surgery, and\u002For treatment)\n* The patient is in a committed relationship\u002Fpartnership with a partner and the partner is available and willing to participate\n* Are English or Spanish speaking\n* ≥ 18 years of age\n* Have access to a smartphone, computer\u002Flaptop or internet connection to complete all study procedures\n\nExclusion Criteria:\n\n* Significant cognitive impairment\n* Inpatient psychiatric treatment for severe mental illness or overt signs of severe psychopathology (e.g., psychosis)\n* Visual, hearing, voice, or motor impairment that prevents completion of study procedures as evidenced by clinical judgment\n* Committed partners will be excluded from the study if they:\n\n  * Refuse to complete informed consent\n  * Have cognitive impairment\n  * Have severe mental illness that would prevent informed consent and completion of study activities as evidenced by clinical judgment",{"count":367,"type":21},160,"OBSERVATIONAL","This study evaluates how useful and acceptable the components of the \"Couples Coping Together Against Cancer\", referred to as \"The Program\", are to the participants with cancer.",[371,28,372,373,374],"Anatomic Stage IV Breast Cancer AJCC v8","Lung Carcinoma","Malignant Solid Neoplasm","Metastatic Breast Carcinoma","2026-06-18",{"date":133,"type":45},{"date":378,"type":45},"2024-07-05",{"date":380,"type":21},"2026-11-16",{"name":382,"class":52},"City of Hope Medical Center",{"id":384,"slug":4,"hasResults":11,"nctId":385,"briefTitle":386,"officialTitle":387,"acronym":4,"eligibilityCriteria":388,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":389,"targetDuration":4,"studyType":22,"phases":390,"briefSummary":391,"conditions":392,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":375,"lastUpdatePostDateStruct":393,"startDateStruct":394,"completionDateStruct":395,"leadSponsor":397,"locationsCount":113},"100622749","NCT07387666","Imaging Acetadote Metabolism in Glioblastoma","A Prospective, Open-label Phase 0 Single-center Study to Assess the Effect of Acetadote on Metabolism in Newly Diagnosed Glioblastoma","Inclusion Criteria:\n\n* 1\\. Glioblastoma\n* 2\\. Newly diagnosed with no prior surgery, radiation, chemotherapy, or other tumor-treating agent\n* 3\\. Age ≥18 years\n* 4\\. KPS \\> 70\n* 5\\. Adequate organ and marrow function as defined below:\n* \\- Bilirubin ≤1.5 times upper limit of normal\n* \\- AST and ALT ≤ 3 times ULN\n* \\- Creatinine ≤ 1.5 x ULN and\u002For GFR ≤ 60 mL\u002Fmin\n* -ANC ≥ 1000 cells\u002Ful\n* \\- Platelet ≥ 100,000\u002Ful\n* \\- Hemoglobin ≥ 9 g\u002Fdl\n* 6\\. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.\n* 6a. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:\n* \\- Has not undergone a hysterectomy or bilateral oophorectomy; or\n* \\- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).\n* 7\\. Ability to understand and the willingness to sign a written informed consent.\n\nExclusion Criteria:\n\n* 1.Chemotherapy, radiotherapy, or other cancer therapy within 4 weeks prior to starting study treatment.\n* 2\\. Subjects must have recovered from prior treatment-related toxicities to grade 2 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism from prior immune checkpoint inhibitor treatment).\n* 3\\. Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.\n* 4\\. Brain metastases\n* 5\\. History of allergic or hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to Acetadote.\n* 6\\. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that, in the opinion of the investigator, would limit compliance with study requirements.\n* 7\\. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.",{"count":223,"type":21},[92],"This goal of this clinical trial is to evaluate how Acetadote affects metabolism in patients with glioblastoma. Drugs like Acetadote, which affect the level of damage in a cell (oxidative stress), may impact brain tumor metabolism and slow the growth of brain tumors.\n\nThe investigators are evaluating how Acetadote affects glioblastoma metabolism by using MRI-based methods and by determining the changes in metabolism in brain tumor tissue resected from patients with a new diagnosis of glioblastoma.",[28,67],{"date":292,"type":45},{"date":375,"type":45},{"date":396,"type":21},"2028-07-01",{"name":398,"class":52},"University of Texas Southwestern Medical Center",{"id":400,"slug":4,"hasResults":11,"nctId":401,"briefTitle":402,"officialTitle":403,"acronym":4,"eligibilityCriteria":404,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":405,"targetDuration":4,"studyType":22,"phases":407,"briefSummary":408,"conditions":409,"keywords":410,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":419,"lastUpdatePostDateStruct":420,"startDateStruct":421,"completionDateStruct":423,"leadSponsor":425,"locationsCount":113},"100623155","NCT07392957","Safety and Efficacy of CTX-009 With or Without CTX-471 for Recurrent Glioblastoma","A Phase IB\u002FII Open-label Study of the Safety and Preliminary Efficacy of CTX-009 Administered Either as a Monotherapy or in Combination With CTX-471 in Patients With Recurrent Glioblastoma","Inclusion Criteria:\n\n* Histologically or radiographically confirmed recurrent CNS WHO grade 4 IDH wild-type glioma following standard of care treatment including radiation, chemotherapy, and\u002For tumor-treating fields. No more than 2 recurrences are allowed.\n* Patients may receive palliative treatment for recurrent disease prior to study enrollment with surgery or laser thermal ablation but must wait at least 4 weeks post-procedure to start study drug(s) and must have recovered from all procedure-related complications.\n* At least 18 years of age.\n* KPS performance status ≥ 60%\n* Adequate bone marrow and organ function as defined below:\n\n  * Absolute neutrophil count ≥ 1.0 K\u002Fcumm\n  * Platelets ≥ 75 K\u002Fcumm\n  * Hemoglobin ≥ 8.0 g\u002FdL\n  * Total bilirubin ≤ 1.5 x IULN, unless suspected or documented history of Gilbert's Syndrome, in which case ≤ 2.5 x IULN\n  * AST(SGOT)\u002FALT(SGPT) ≤ 2.5 x IULN\n  * Creatinine clearance \\> 30 mL\u002Fmin by Cockcroft-Gault\n  * Urine Protein : Creatinine ratio (UPCR) \\\u003C 300 mg\u002Fg\n* QTcF \\\u003C 480 msec; in the setting of bundle branch block or other arrhythmia that makes QTcF unreliable, a JT interval \\\u003C 350 msec can be used as a substitute.\n* The effects of CTX-009 and CTX-471 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 4 months after completion of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s\u002Fhe must inform her treating physician immediately.\n* Resolution, or stable control with medical management, of all prior anti-cancer therapy toxicities to ≤ grade 1 per NCI-CTCAE v5.0. If the patient has had major surgery, 4 weeks must have elapsed from the date of surgery and the first dose of study drug(s).\n* Stable or decreasing dose of corticosteroids and anti-seizure medications for 7 days prior to start of study drug(s). For Arm 2: a maximum of 2 mg daily dose of dexamethasone or equivalent at time of study drug(s) initiation is allowed.\n* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.\n\nExclusion Criteria:\n\n* Have progressed on prior anti-VEGF-A therapy (i.e., bevacizumab) or developed clinically significant adverse reaction to any anti-VEGF therapy (i.e., bevacizumab, regorafenib) which led to discontinuation of treatment. Prior treatment with low dose anti-VEGF therapy for management of symptomatic vasogenic edema or radiation necrosis is permitted as long as progression was not noted while receiving treatment with the anti-VEGF agent, and is not needed for continued control of symptoms. A 4-week washout from last dose of low-dose anti-VEGF therapy is required.\n* Prior systemic anti-cancer therapy including: investigational agents or immunotherapy within 4 weeks (can consider 2 week interval for agents with known 5 half-lives \\\u003C14 days following discussion with study PI); chemotherapy within 4 weeks (6 weeks for BCNU or CCNU); or targeted therapy within 2 weeks prior to treatment.\n\nNote: participants must have recovered from all clinically significant AEs due to previous therapies to ≤ grade 1 or baseline. This does not include AEs deemed not clinically significant by treating physician (i.e., alopecia). Participants with endocrine-related AEs ≤ grade 2 requiring treatment or hormone replacement are eligible if controlled (i.e., clinically asymptomatic) on stable dose of replacement therapy.\n\n* Use of aspirin, NSAIDs, or other antiplatelet agents within 7 days of study drug(s) initiation. Regular use (i.e., daily) of these agents should be avoided while on study treatment.\n* Use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes within 7 days of study drug(s) initiation. Prophylactic dosing of DOAC, such as apixaban or edoxaban, or LMWH for patency of venous access devices is allowed (preference is given to DOAC over LMWH).\n* History of intraparenchymal or subdural hemorrhage. History of hemorrhage-related or gastroenterological disease including active hemorrhage, hemorrhagic diathesis, coagulopathy, or tumor in great arteries. History of clinically significant gastroenterological disease, such as peptic ulcer, GI bleeding, GI or non-GI fistula, perforation, abdominal abscess, percutaneous drains, clinical symptoms and signs of GI obstruction, need for parenteral hydration or nutrition, or inflammatory bowel disease (IBD).\n* History of unprovoked high-risk thromboembolic events.\n* A history of the following cardiovascular diseases in the past 5 years (a case-by-case evaluation can be considered in consultation with the study PI):\n\n  * Congestive heart failure that corresponds to Class II or a higher class under NYHA classification or \\\u003C 50% of LVEF\n  * Uncontrolled hypertension (140\u002F90 mmHg despite best care including anti-hypertensive medications). White coat hypertension is not exclusionary.\n  * Hypertensive crisis or pre-existing hypertensive encephalopathy\n  * Pulmonary hypertension\n  * Myocardial infarction\n  * Uncontrolled arrhythmia\n  * Unstable angina\n* Significant vascular diseases (e.g., aortic aneurysm requiring surgery or recent peripheral artery thrombosis) within 6 months prior to study entry\n* For Arm 2: Prior treatment with other investigational immune-oncology therapies targeting CD137 (4-1BB).\n* For Arm 2: Systemic therapy with non-steroidal immunosuppressive agents within 7 days prior to first dose. Patients with a prior history of autoimmune disease not requiring immunosuppressive therapy may be eligible following discussion with the study PI. Topical, intranasal, intraocular, or inhaled corticosteroids and physiologic replacement for patients with adrenal insufficiency are allowed.\n* Prior solid organ or hematologic cell transplantation.\n* For Arm 2: Has received a live or live-attenuated vaccine within 30 days prior to the first dose. Note: administration of killed vaccines is allowed.\n* Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.\n* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to CTX-009 or CTX-471.\n* Active uncontrolled seizure disorder.\n* Active uncontrolled intercurrent illness including, but not limited to: infection, hypertension, open wound(s), or cardiac arrhythmia. Chronic illnesses controlled (i.e., clinically asymptomatic) with oral medications are allowed.\n* Pregnant and\u002For breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose for Arm 1 or 72 hours of first dose for Arm 2.\n* HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.\n* Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.\n* History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.",{"count":406,"type":21},54,[225,24],"This is a phase IB\u002FII, open-label study evaluating CTX-009 as monotherapy and in combination with CTX-471. The study evaluates the safety and efficacy of the monotherapy and the combination in patients with recurrent glioblastoma. The study tests the hypothesis that treatment with CTX-009 alone or in combination with CTX-471 will lead to enhanced tumor control and prolongation of overall survival of patients with recurrent glioblastoma.\n\nCTX-009 expands on existing anti-angiogenic therapies by ablating key compensatory and resistance mechanisms to bevacizumab, CTX-471 restores local immune reactivity through activation of costimulatory immune mediators. Combination of these two agents may further impair tumor proliferation through synergistic effects on the tumor microenvironment",[28],[411,412,413,414,415,416,417,418],"VEGF","4-1BB","CD137","glioblastoma","immunotherapy","targeted therapy","CTX-009","CTX-471","2026-06-17",{"date":258,"type":45},{"date":422,"type":45},"2026-06-16",{"date":424,"type":21},"2031-06-30",{"name":426,"class":52},"Washington University School of Medicine",{"id":428,"slug":4,"hasResults":11,"nctId":429,"briefTitle":430,"officialTitle":431,"acronym":4,"eligibilityCriteria":432,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":433,"targetDuration":4,"studyType":22,"phases":435,"briefSummary":436,"conditions":437,"keywords":439,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":419,"lastUpdatePostDateStruct":442,"startDateStruct":443,"completionDateStruct":445,"leadSponsor":447,"locationsCount":113},"100485925","NCT05607407","Methimazole in Patients With Progressive Glioblastoma","Targeting Transsulfuration Via Suppression of Thyroid Hormone Signaling in Progressive Glioblastoma: Phase 2 and Pharmacodynamic Trial of Methimazole in Patients With Progressive Glioblastoma","Inclusion Criteria:\n\n* Subjects must have histologically or cytologically confirmed WHO grade 4 glioma (including tumors with molecularly defined grade 4 astrocytoma) for which a clinically indicated tumor resection is planned.\n* Subjects must not have received methimazole for this disease.\n* Age is greater than or equal to 18 years of age\n* Performance status: Karnofsky Performance status ≥ 70%\n* Subjects must have adequate organ function and laboratory parameters within 21 days of study entry as defined below: Hemoglobin ≥ 8 g\u002Fdl, Absolute neutrophil count ≥ 1,200\u002FmcL, Platelet count ≥ 75,000\u002FmcL, Total bilirubin \\\u003C 1.5 x institutional upper limit of normal (ULN), AST (SGOT) ≤ 3 X institutional ULN, ALT (SGPT) ≤ 3 X institutional ULN, Calculated creatinine clearance \\> 50 mL\u002Fmin, Prothrombin time\u002Finternational normalized ratio (PT\u002FINR) \\\u003C1.4 for patients not on warfarin, Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria: No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices), In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin\n* Subjects must have normal thyroid function within 21 days of study entry as defined below: ≤ 3 X institutional ULN\n* Women of childbearing potential must have a negative pregnancy test within 21 days of study entry. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men of reproductive potential treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug.\n* Patients must be able to swallow whole tablets.\n* Patients must have the following minimum intervals from prior treatments: surgery - 4 weeks, nitrosoureas - 6 weeks, cytotoxic chemotherapy - standard intervals depending on the most recent regimen. i.e., for temozolomide 5 of 28, 23 days after most recent temozolomide; for temozolomide 21 of 28 days, 7 days after most recent dose; etoposide 14 of 21 days, 7 days after last dose. For drugs not listed, the research nurse, treating investigator, and principal investigator will determine the appropriate interval, Investigational therapy or non-cytotoxic therapy - 2 weeks, For bevacizumab - 4 weeks from anticipated date of protocol surgery\n* Patients positive for human immunodeficiency virus (HIV) are allowed on study (note: HIV testing is not required), but HIV-positive patients must have: An undetectable viral load within 6 months of registration, A stable regimen of highly active anti-retroviral therapy (HAART), No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections\n* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n* For patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load\n* Patient must be deemed by investigator to be a candidate for post-operative chemotherapy.\n* Subjects must have the ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Prior treatment toxicities not resolved to ≤ Grade 1 according to NCI CTCAE Version 5.0 except alopecia and neuropathy.\n* Subjects receiving any other investigational agents.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to methimazole.\n* Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Other prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are excluded. Otherwise, patients with prior or concurrent malignancy are eligible.\n* Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute \\[NCI\\] Common Terminology Criteria for Adverse Events Version 5.0 \\[CTCAE v.5.0\\] diarrhea of any etiology at screening).\n* Pregnant or breastfeeding.\n* Known history of hyperthyroidism or hypothyroidism\n* Unable or unwilling to swallow tablets.\n* Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness\u002Fsocial situations that would, in the Investigator's judgment, make the patient inappropriate for this study.",{"count":434,"type":21},19,[24],"The purpose of this study is to test the effectiveness, safety, and tolerability of a drug called Methimazole. The investigational drug, Methimazole is not FDA approved for brain tumors, but it is used to treat thyroid illnesses. Different doses of Methimazole will be given to several study participants with glioblastoma. The first several study participants will receive the lowest dose. If the drug does not cause serious side effects, it will be given to other study participants at a higher dose. The doses will continue to increase for every group of study participants until the side effects occur that require the dose to be lowered. The procedures in this study are research blood draws, physical exams, collection of medical history, MRI scans, and study drug administration.",[28,438],"Glioma",[440,441],"Transsulfuration","Methimazole",{"date":375,"type":45},{"date":444,"type":45},"2023-01-30",{"date":446,"type":21},"2026-09",{"name":215,"class":52},{"id":449,"slug":4,"hasResults":11,"nctId":450,"briefTitle":451,"officialTitle":452,"acronym":4,"eligibilityCriteria":453,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":454,"targetDuration":4,"studyType":22,"phases":456,"briefSummary":457,"conditions":458,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":461,"lastUpdatePostDateStruct":462,"startDateStruct":463,"completionDateStruct":465,"leadSponsor":467,"locationsCount":113},"100634599","NCT07541781","Sitagliptin in Recurrent\u002FProgressive Grade 4 Glioma","Targeting Myeloid-Derived Suppressor Cells in Patients With Recurrent\u002FProgressive Grade 4 Glioma: Phase 1 Trial of Sitagliptin","Inclusion Criteria:\n\nPhase 1b\n\n* Subjects must have histologically or cytologically confirmed WHO grade 4 glioma for which disease recurrence\u002Fprogression after first line therapy is diagnosed by the treating physician.\n* Subjects must not have received sitagliptin or bevacizumab for this disease.\n* Age \\>18 years\n* Performance status: ECOG performance status 0-2\n* Subjects must have adequate organ function and laboratory parameters within 21 days of study entry as defined below:\n\n  1. Hemoglobin ≥ 9 g\u002Fdl\n  2. Absolute neutrophil count ≥ 1,500\u002FmcL\n  3. Platelet count ≥ 100,000\u002FmcL\n  4. Total bilirubin \\\u003C 1.5 x institutional upper limit of normal (ULN)\n  5. AST (SGOT) ≤ 3 X institutional ULN\n  6. ALT (SGPT) ≤ 3 X institutional ULN\n  7. Calculated creatinine clearance \\> 50 mL\u002Fmin\n  8. Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio.\n\n     For UPC ratio \\> 0.5, 24-hour urine protein must be obtained and must be \\\u003C 1000 mg.\n  9. Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:\n\n     * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)\n     * In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin\n* Subjects must have the ability to understand and the willingness to sign a written informed consent document.\n* Women of childbearing potential, defined as any female who has experienced menarche and has not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy) and is not postmenopausal (≥12 months of spontaneous amenorrhea without an alternative medical cause), must have a negative pregnancy test within 7 days prior to treatment start. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug.\n* Subjects must be able to swallow whole tablets.\n* Participants must have controlled blood pressure, defined as systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 100 mg Hg, with or without antihypertensive therapy\n* Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior study treatment\n* Subjects must have the following minimum intervals from prior treatments until planned treatment initiation of Cycle 1 Day 1:\n\n  * surgery - 4 weeks\n  * nitrosoureas - 6 weeks\n  * cytotoxic chemotherapy - standard intervals depending on the most recent regimen. i.e., for temozolomide 5 of 28, 23 days after most recent temozolomide; for temozolomide 21 of 28 days, 7 days after most recent dose; etoposide 14 of 21 days, 7 days after last dose.\n  * For drugs not listed, the research nurse, treating investigator, and principal investigator will determine the appropriate interval.\n  * Investigational therapy or non-cytotoxic GBM related therapy - 2 weeks\n* Subject is not deemed as a surgical candidate.\n\nPilot Phase\n\n* Subjects must have histologically or cytologically confirmed WHO grade 4 glioma for which disease recurrence\u002Fprogression after first line therapy is diagnosed by the treating physician.\n* Subjects must not have received sitagliptin or bevacizumab for this disease.\n* Age \\>18 years\n* Performance status: ECOG performance status 0-2\n* Subjects must have adequate organ function and laboratory parameters within 21 days of study entry as defined below:\n\n  1. Hemoglobin ≥ 9 g\u002Fdl\n  2. Absolute neutrophil count ≥ 1,500\u002FmcL\n  3. Platelet count ≥ 100,000\u002FmcL\n  4. Total bilirubin \\\u003C 1.5 x institutional upper limit of normal (ULN)\n  5. AST (SGOT) ≤ 3 X institutional ULN Version date: 30March2026 Page 16\n  6. ALT (SGPT) ≤ 3 X institutional ULN\n  7. Calculated creatinine clearance \\> 50 mL\u002Fmin\n  8. Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio.\n\n     For UPC ratio \\> 0.5, 24-hour urine protein must be obtained and must be \\\u003C 1000 mg.\n  9. Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria:\n\n     * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)\n     * In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin\n* Subjects must have the ability to understand and the willingness to sign a written informed consent document.\n* Women of childbearing potential, defined as any female who has experienced menarche and has not undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy) and is not postmenopausal (≥12 months of spontaneous amenorrhea without an alternative medical cause), must have a negative pregnancy test within 7 days of treatment start. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug.\n* Subjects must be able to swallow whole tablets.\n* Subjects must have controlled blood pressure, defined as systolic blood pressure ≤ 160 mg Hg or diastolic pressure ≤ 100 mg Hg, with or without antihypertensive therapy\n* Electrocardiogram without evidence of acute cardiac ischemia within 14 days prior to treatment start\n* Subjects must have the following minimum intervals from prior treatments until planned treatment initiation of Cycle 1Day1:\n\n  * surgery - 4 weeks\n  * nitrosoureas - 6 weeks\n  * cytotoxic chemotherapy - standard intervals depending on the most recent regimen. i.e., for temozolomide 5 of 28, 23 days after most recent temozolomide; for temozolomide 21 of 28 days, 7 days after most recent dose; etoposide 14 of 21 days, 7 days after last dose.\n  * For drugs not listed, the research nurse, treating investigator, and principal investigator will determine the appropriate interval.\n  * Investigational therapy or GBM related non-cytotoxic therapy - 2 weeks\n  * For bevacizumab (if for a different cancer) - 4 weeks from the expected date of protocol surgery\n* Subject is deemed as a surgical candidate.\n\nExclusion Criteria (for phase 1b and pilot phase)\n\n* Prior treatment toxicities not resolved to ≤ Grade 1 according to NCI CTCAE Version 5.0 except for alopecia and neuropathy.\n* Subjects receiving any other investigational agents.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to sitagliptin or bevacizumab.\n* Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Known HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with sitagliptin and\u002For bevacizumab. In addition, these subjects are at increased risk of lethal infections when treated with marrow suppressive therapy.\n* Other malignancy within the past 2 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or vulva; c) prostate cancer of Gleason Score 6 or less with stable prostate specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder, or benign tumors of the adrenal or pancreas.\n* Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute \\[NCI\\] Common Terminology Criteria for Adverse Events Version 5.0 \\[CTCAE v.5.0\\] diarrhea of any etiology at screening).\n* Known active infection with hepatitis B or hepatitis C virus.\n* Pregnant or breastfeeding.\n* Subjects who receive insulin or sulfonylurea for diabetes mellitus.\n* Subjects with history of type 1 diabetes, uncontrolled type 2 diabetes, hypoglycemia requiring medical intervention, or those who are deemed not suitable to receive sitagliptin at the discretion of the investigators.\n* Unable or unwilling to swallow tablets.\n* Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness\u002Fsocial situations that would, in the Investigator's judgment, make the patient inappropriate for this study.\n* Arterial ischemic event (e.g., unstable angina, myocardial infarction, stroke) within 6 months of study consent.\n* Subjects with history of hematologic bleeding disorder.",{"count":455,"type":21},45,[225],"Sitagliptin, when combined with standard-of-care drug bevacizumab, is being tested to 1) find out if it is effective at treating gliomas that have returned or progressed after treatment, and 2) find out what the highest dose of sitagliptin is appropriate to give when combined with bevacizumab.",[438,28,459,66,460],"Recurrent Glioma","Grade 4 Malignant Glioma of Brain (Disorder)","2026-06-15",{"date":419,"type":45},{"date":464,"type":45},"2026-06-11",{"date":466,"type":21},"2030-06-11",{"name":468,"class":52},"Kailin Yang, MD, PhD",{"id":470,"slug":4,"hasResults":11,"nctId":471,"briefTitle":472,"officialTitle":473,"acronym":4,"eligibilityCriteria":474,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":475,"targetDuration":4,"studyType":22,"phases":477,"briefSummary":478,"conditions":479,"keywords":4,"overallStatus":188,"whyStopped":4,"lastUpdateSubmitDate":464,"lastUpdatePostDateStruct":480,"startDateStruct":481,"completionDateStruct":483,"leadSponsor":485,"locationsCount":113},"100550531","NCT06448286","PH Weighted Chemical Exchange Saturation Transfer MRI-Based Surgical Resection to Improve Survival in Patients With Glioblastoma","PH Weighted Chemical Exchange Saturation Transfer Based Surgical Resections of Glioblastoma","Inclusion Criteria:\n\n* Male or female ≥ 18 years of age\n* Documentation of a newly diagnosed World Health Organization (WHO) grade IV glioblastoma as evidenced by clinical features and imaging data\n* Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study\n\nExclusion Criteria:\n\n* Male or female \\\u003C 18 years of age\n* Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data\n* Not medically cleared for surgery\n* Previous treatment (any chemotherapy, molecular therapy, immunotherapy, or radiation therapy)",{"count":476,"type":21},60,[25],"This phase III trial compares pH weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI)-based surgical resections to standard of care surgical resections for the treatment of patients with glioblastoma. Standard of care therapy for glioblastoma is surgery to remove tumor tissue that enhances on standard MRI imaging, however, it has been shown that significant tumor burden exists in the region around the tumor tissue that does not enhance with standard MRI. MRI is a procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and tumor tissue. CEST MRI is a technique that uses differences in the tissue environment, like protein concentration or intracellular pH, to generate contrast differences. CEST MRI may identify tumor tissue that does not enhance with standard of care MRI. PH weighted CEST MRI based surgical resection may be more effective compared to standard of care surgical resection in treating patients with glioblastoma.",[28],{"date":461,"type":45},{"date":482,"type":21},"2026-12-01",{"date":484,"type":21},"2030-06-01",{"name":486,"class":52},"Jonsson Comprehensive Cancer Center",{"id":488,"slug":4,"hasResults":11,"nctId":489,"briefTitle":490,"officialTitle":491,"acronym":4,"eligibilityCriteria":492,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":493,"targetDuration":4,"studyType":22,"phases":494,"briefSummary":495,"conditions":496,"keywords":498,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":504,"lastUpdatePostDateStruct":505,"startDateStruct":507,"completionDateStruct":509,"leadSponsor":511,"locationsCount":513},"100587938","NCT06934889","Study of ABBV-637 or ABBV-155 With ERAS-801 for People With Glioblastoma","Phase Ib Trial of ABBV-637 or ABBV-155 in Combination With ERAS-801 for Glioblastoma With Amplification of the Epidermal Growth Factor Receptor","Inclusion Criteria:\n\n* Patients must be 18 years of age or older at the time of consent signing.\n* All Patients must have WHO Grade IV Glioblastoma\u002FGliosarcoma using WHO 2021 criteria and include the diagnosis of molecular GBM, recurrent patients must be progressive or recurrent following radiation therapy +\u002F- chemotherapy\n* Patients must be IDH wild type by CLIA-certified laboratory assay available at time of consent.\n* Patients must have evidence of EGFR gene amplification by CLIA-certified laboratory assay at time of consent.\n* Patients must have measurable disease as per RANO criteria pre-operatively (there is no requirement for post-operative disease to be present or absent). \\[cohort A\u002FB only\\]\n* Patients must be able to tolerate MRIs\n* Patients may have no more than 2 prior therapy regimens. \\[cohort A\u002FB only\\]\n* Patients must have recovered from severe toxicity of prior therapy. The following intervals from previous treatments are required to be eligible:\n\n  1. 12 weeks from the completion of radiation\n  2. 6 weeks from a nitrosourea chemotherapy\n  3. 3 weeks from a non-nitrosourea chemotherapy\n  4. 4 weeks from any investigational (not FDA-approved) agents\n  5. 6 months from the last treatment with bevacizumab\n  6. 2 weeks or 5 half-lives from administration of a non-cytotoxic, Chemotherapies other than bevacizumab, whichever is shorter\n* Patients must be undergoing surgery that is clinically indicated as determined by their care providers. \\[cohort A\u002FB only\\] Patients must be eligible for surgical resection according to the following criteria:\n\n  a. Expectation that the surgeon is able to resect at least 500 mg of tumor from enhancing tumor with low risk of inducing neurological injury.\n* Paraffin embedded tissue must be available from initial surgical resection at diagnosis (prior to any treatment). The following amount of tissue is requested: 1 formalin-fixed, paraffin embedded (FFPE) tissue block (preferred) or 10 FFPE unstained slides (5µm thick).\n* Patients must have a Karnofsky Performance Status (KPS) ≥60% (i.e. the patient must be able to care for himself\u002Fherself with occasional help from others).\n* Patients must have the following organ and marrow function:\n\n  1. Absolute neutrophil count \\>1,200\u002FmcL\n  2. Platelets \\>100,000\u002FmcL\n  3. Hemoglobin \\> 9 g\u002FdL .\n  4. Total bilirubin ≤ institutional upper limit of normal, or ≤ 3.0 mg\u002FdL for subjects with Gilbert's syndrome\n  5. AST (SGOT) and ALT (SGPT) ≤ 3 × institutional upper limit of normal\n  6. Creatinine ≤ institutional upper limit of normal OR Creatinine clearance \\>60 ml\u002Fmin\u002F1.73m2 for patients with creatinine levels above institutional normal\n  7. APTT\u002FPTT ≤ 1.5 x institutional upper limit of normal\n* Echocardiogram with ejection fraction ≥ 50% and no other clinically significant finding that, in the opinion of the investigator, would increase the subject's susceptibility to cardiac toxicity.\n\n  a. If ECHO cannot be performed for structural or safety reasons, a MUGA may be obtained instead after discussion with treating investigator.\n* Patients must have a 12-lead electrocardiogram performed within 2 weeks of treatment start with QT interval corrected for heart rate (QTc) \\\u003C 450 msec (using Fridericia's correction), and no clinically significant abnormalities. (Cohorts A, B, E \\& F only)\n* Women of childbearing potential must have a negative serum pregnancy test prior to study entry. Women of childbearing potential and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after completion of treatment administration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.\n* A negative serum pregnancy test for all female subjects (except postmenopausal) at the screening visit and a negative urine pregnancy test for all female subjects (except postmenopausal) at baseline before the first dose of study drug.\n* If female, subject must be either postmenopausal, OR permanently surgically sterile OR, for women of childbearing potential, practicing at least 1 protocol-specified method of birth control that is effective from study Day 1 through at least 4 months after the last dose of study drug.\n* If male, and subject is sexually active with female partner(s) of childbearing potential, he must agree from study Day 1 through 4 months after the last dose of study drug to practice the protocol-specified contraception.\n* If female, subject must not be pregnant, breastfeeding, or considering becoming pregnant during the study while receiving study drug and for at least 4 months after the last dose of study drug.\n* If male, subject must not be considering fathering a child or donating sperm during the study or for 4 months after the last dose of study drug.\n* No known active viral hepatitis infection (including hepatitis B and C) or human immunodeficiency virus (HIV) with the following exceptions:\n\n  * Subjects with a history of hepatitis B that is considered cured may be enrolled at the discretion of the treating investigator.\n  * Subjects with a history of hepatitis C that is considered cured with definitive therapy may be enrolled at the discretion of the treating investigator.\n  * Subjects with HIV and undetectable viral load, so long as ongoing antiretroviral therapy does not pose risk of adverse drug-drug interactions, at the discretion of the treating investigator.\n* Patients must have no concurrent malignancy that requires active therapy.\n* Patients must be able to swallow medication by mouth, either tablets or dispersed in solution.\n\nExclusion Criteria:\n\n* Patients may not be receiving any other investigational agents.\n* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the investigational agents are ineligible.\n* Patients with prior therapy with EGFR targeting agents are ineligible because treatment with EGFR kinase inhibitors or other EGFR-targeted agents has the potential to deplete the tumor of EGFR-amplified or EGFR mutant cell populations and confound the evaluation of the investigational regimen. Patients would only be eligible if surgery on a recurrence after the EGFR-targeted therapy confirmed persistence of an EGFR alteration.\n* Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol. Patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs. Patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of study drug(s).\n* Patients must not have evidence of significant hematologic, renal, or hepatic dysfunctioPatients must not have evidence of significant intracranial hemorrhage (For example, in the recurrent setting, circumstances where the intracranial hemorrhage would obscure the amount and quality of tissue obtained at the time of the on-treatment surgery).\n* Patients with uncontrolled intercurrent illness including, but not limited to, hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002F social situations that would limit compliance with study requirements, are ineligible.\n* Participants with clinically significant cardiovascular disease including, but not limited to:\n\n  * No recent history (within 6 months) of congestive heart failure (defined as New York Heart Association, Class 2 or higher), ischemic cardiovascular event, cardiac arrhythmia requiring pharmacological or surgical intervention, pericardial effusion, or pericarditis.\n  * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, e.g., complete left bundle branch block, second- or third-degree heart block, PR-interval \\> 250 ms.\n  * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, or any concomitant medication know to prolong the QT interval.\n* No history of clinically significant medical and\u002For psychiatric conditions or any other reason that, in the opinion of the investigator, would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug\n* Pregnant women are excluded from this study because the investigational regimens have potential for teratogenic or abortifacients effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated on this study.\n* HIV-positive patients on strong CYP3A4 inducers or inhibitors are ineligible because of the potential for pharmacokinetic interactions.\n* Patients who have acute or currently active\u002Frequiring anti-viral therapy hepatic or biliary disease are ineligible (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases from the primary brain tumor, or stable chronic liver disease per investigator assessment).\n* Patients receiving P-gp inhibitors\u002FP-gp substrates with narrow therapeutic index are ineligible.\n* Patients who are receiving a drug that has a risk of QTc prolongation with known risk of if QTc is ≥ 460 msec. are ineligible. (Temozolomide is allowed for cohorts C,D, E and F)\n* Subject must not have systemically used known moderate or strong cytochrome P450 (CYP)3A inhibitors within 10 days before the first dose of study drug and throughout the study.\n* Subject must not have received any live vaccine within 2 weeks before the first dose of study drug, or be expected to need a live vaccination during study participation including at least 4 weeks after the last dose of study drug.",{"count":476,"type":21},[225],"The researchers are doing this study to find out whether the drugs ABBV-637 and ABBV-155 are safe treatments that cause few or mild side effects when given alone or in combination with ERAS-801 in people with recurrent GBM.",[28,497],"Gliosarcoma",[499,500,501,502,503],"WHO grade IV","ABBV-637","ABBV-155","ERAS-801","24-409","2026-06-09",{"date":506,"type":45},"2026-06-10",{"date":508,"type":45},"2025-04-07",{"date":510,"type":21},"2028-04",{"name":512,"class":52},"Memorial Sloan Kettering Cancer Center",11,{"id":515,"slug":4,"hasResults":11,"nctId":516,"briefTitle":517,"officialTitle":518,"acronym":4,"eligibilityCriteria":519,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":520,"targetDuration":4,"studyType":22,"phases":521,"briefSummary":522,"conditions":523,"keywords":529,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":504,"lastUpdatePostDateStruct":546,"startDateStruct":547,"completionDateStruct":549,"leadSponsor":551,"locationsCount":553},"100461030","NCT05283330","Safety and Tolerability of ²¹²Pb-DOTAM-GRPR1 in Adult Subjects With Recurrent or Metastatic GRPR-expressing Tumors","A Phase 1 Open-Label, First-in-human, Dose Escalation and Expansion Study to Determine the Safety, Tolerability, Dosimetry, Pharmacokinetics, and Preliminary Efficacy of 212Pb-DOTAM-GRPR1 in Adult Participants With Recurrent or Metastatic GRPR-expressing Tumors","1. Adult participants (age ≥ 18 years old) with any of the following advanced or metastatic solid tumors (documented history of histologically confirmed diagnosis):\n\n   1. Metastatic castration-resistant prostate cancer (mCRPC) including neuroendocrine prostate cancer (NEPC) (enrolled only in SAD and MAD Q6W)\n   2. HR+\u002FHER2- breast cancer (estrogen receptor\u002FER expression \\>10% of tumor cell nuclei stain, regardless of progesterone receptor\u002FPgR expression); HER2-negative including HER2-low (as per relevant ASCO\u002FCAP guidelines)\n   3. Colorectal cancer\n   4. Cervical cancer\n   5. Non-small-cell lung cancer (NSCLC)\n   6. Recurrent glioblastoma (only enrolled in MAD Q4W cohorts) with evidence of recurrent disease (RD) demonstrated by disease progression using modified Response Assessment in Neuro-Oncology (RANO 2.0) criteria. Note: If surgery is performed for GBM recurrence, pre-surgery MRI will be used for confirmation of RD and residual and measurable disease post-surgery is not required but surgery must have confirmed the recurrence diagnosis by MRI.\n2. Capable of giving signed informed consent\n3. All participants must have progressed on at least 2 prior systemic therapies, except for recurrent GB\n4. For participants with mCRPC: Prior orchiectomy and\u002For ongoing androgen deprivation therapy and a castrate level of serum testosterone (\\\u003C50 ng\u002FdL or \\\u003C1.7 nmol\u002FL)\n5. Presence of at least 1 measurable lesion per RECIST 1.1 as assessed by the Investigator (not applicable for GBM). At least 1 identified measurable lesion must show GRPR uptake in 203Pb-DOTAM-GRPR1 SPECT\u002FCT (uptake greater than that of the background) as assessed by the Investigator.\n6. For participants with prostate cancer that do not have measurable soft tissue disease, 203Pb-DOTAM-GRPR1 uptake in bone lesions \\> uptake in background is acceptable for eligibility.\n7. Eastern Cooperative Oncology Group (ECOG) status 0-1. Participants with ECOG status of 2 may be approved on a case-by-case basis in discussion with the Sponsor.\n8. Adequate bone marrow, hepatic, and renal function, as assessed by the following laboratory requirements:\n\n   1. White blood cell (WBC) ≥3000\u002F mm3 (≥ 3 x 109\u002FL)\n   2. Absolute neutrophil count (ANC) ≥1500\u002Fmm3 (≥1.5 x 109\u002FL)\n   3. Platelets ≥100,000\u002Fmm3 (≥ 100 x 109\u002FL)\n   4. Hemoglobin (Hb) ≥9.0 g\u002FdL\n   5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3x upper limit of normal (ULN) or ≤ 5 x ULN in the presence of liver metastases\n   6. Total bilirubin: ≤1.5 x ULN, except if documented history of Gilbert's disease who are eligible if total bilirubin ≤ 3 x ULN\n   7. Adequate renal function defined by creatinine clearance (CLCR) ≥ 60 mL\u002Fmin calculated as follows: CLCR = eGFR in ml\u002Fmin\u002F1.73 m2 calculated by the Modified Diet in Renal Disease (MDRD) x participant body surface area (BSA) in m2 ÷ 1.73\n   8. Serum amylase and\u002For lipase ≤1.5 x ULN\n9. For women of childbearing potential (WOCBP) and men with partners of childbearing potential: be willing to use highly effective methods of contraception or sexual abstinence, if part of participant's lifestyle, throughout the study and for 7 months for WOCBP, 4 months for men after the last \\[212Pb\\]Pb-DOTAM-GRPR1 administration or for 10 days following \\[203Pb\\]Pb-DOTAM-GRPR1 administration and participant is not proceeding to 212Pb-DOTAM-GRPR1 treatment, as outlined in protocol.\n\n   Participants with Recurrent Glioblastoma:\n10. Having first or second glioblastoma recurrence, after standard therapy that includes prior radiation therapy (RT) and at least 12 weeks from completion of RT prior to first administration of 212Pb-DOTAM-GRPR1. In case surgery has been performed for GBM recurrence, the surgery has to be completed at least 4 weeks prior to 212Pb-DOTAM-GRPR1 treatment start, with post-surgery recovery without any complications related to surgical procedure.\n11. Presence of 203Pb-DOTAM-GRPR1 uptake by SPECT\u002FCT scan in the tumor lesion(s).\n12. Presence of Gadolinium enhancement in the MRI in the tumor lesion(s) shown at the time of diagnosis of tumor recurrence.",{"count":202,"type":21},[225],"A Phase 1 Open-Label, First-in-human, Dose Escalation and Expansion Study to Determine the Safety, Tolerability, Dosimetry, Pharmacokinetics, and Preliminary Efficacy of 212Pb-DOTAM-GRPR1 in Adult Participants with Recurrent or Metastatic GRPR-expressing Tumors",[524,525,280,526,527,28,528],"Cervical Cancer","Breast Cancer","NSCLC","mCRPC (Metastatic Castration-resistant Prostate Cancer)","Nonsmall Cell Lung Cancer",[530,531,532,533,534,535,536,537,524,538,539,540,541,542,543,544,545],"Metastatic Cancer","Advanced Cancer","Recurrent Cancer","Prostate Cancer, Castration-Resistant","Metastatic Prostate Cancer","Breast Cancer, Hormone Receptor Positive","Non-Small Cell Lung Cancer","Colorectal Cancer","Glioblastoma, Recurrent","Radioligand Therapy","Targeted Radiation Therapy","Gastrin-Releasing Peptide Receptor or Bombesin receptor subtype-2","Targeted Alpha Therapy","Lead-212 Radiopharmaceutical Therapy","Lead-203 Radiopharmaceutical Diagnostic","SPECT\u002FCT",{"date":464,"type":45},{"date":548,"type":45},"2022-12-22",{"date":550,"type":21},"2032-05",{"name":552,"class":82},"Orano Med Theranostics, SAS",8,{"id":555,"slug":4,"hasResults":11,"nctId":556,"briefTitle":557,"officialTitle":558,"acronym":4,"eligibilityCriteria":559,"healthyVolunteers":11,"sex":17,"minAge":560,"maxAge":561,"enrollmentInfo":562,"targetDuration":4,"studyType":368,"phases":4,"briefSummary":564,"conditions":565,"keywords":4,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":568,"lastUpdatePostDateStruct":569,"startDateStruct":570,"completionDateStruct":572,"leadSponsor":574,"locationsCount":575},"100503755","NCT05839379","Targeted Pediatric High-Grade Glioma Therapy","Molecularly-Guided Phase II Umbrella Trial for Children, Adolescents, and Young Adults Newly Diagnosed With High-Grade Glioma, Including Diffuse Intrinsic Pontine Glioma","Inclusion Criteria:\n\n1. Age: Patients must be ≥12 months and ≤39 years of age at the time of enrollment onto this screening protocol.\n2. Diagnosis: Patients with newly diagnosed HGG, including DIPG are eligible. Diagnosis must have histologic confirmation from biopsy or resection. The diagnosis of HGG must have been confirmed by pathology review at the local site. For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology consistent with diffuse WHO grade 2-4 glioma (eg, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, H3K27-altered diffuse midline glioma). For all other tumors, histologic grade must be WHO grade 3-4.\n3. Disease Status: There are no disease status requirements for enrollment.\n\n   * Measurable disease is not required. Patients without measurable disease are eligible.\n   * Patients with metastatic\u002Fdisseminated or multifocal disease or gliomatosis cerebri are eligible.\n   * Patients with a primary spinal tumor are eligible.\n   * Patients with secondary, radiation related HGG are eligible.\n4. Prior Therapy for HGG: Surgery, radiation, and\u002For dexamethasone are permissible. Temozolomide concurrent with radiation is permissible. Prior administration of avastin\u002Fbevacizumab is allowed (individual treatment arms have different washout period requirements, check individual arm eligibility). No other prior anticancer therapy for HGG will be allowed.\n\n   * Participants screening for assignment to TarGeT-L may not have received radiation.\n\n   Timing from surgery to start of RT: For patients who have started RT, radiation must have started \\\u003C42 days from definitive surgery or biopsy, however it is strongly recommended patients start RT within 31 days from definitive surgery (if patient had two surgeries, radiation must have started within 31 days from second surgery).\n5. Tumor Sample Availability OR results from previous molecular profiling\u002Ftargeted sequencing\n\n   * If a patient screens through OPTION #1, tumor sample in addition to normal comparator tissue (peripheral blood, saliva, or buccal swab) must be submitted for comprehensive molecular screening at the time of screening enrollment.\n   * If a patient screens through OPTIONS #2 or #3, results from previously performed molecular profiling must be submitted following enrollment. It is highly recommended that results be uploaded within 7 days of enrollment (if results are available at time of enrollment) or within 7 days of results becoming available (if pending at time of enrollment) to allow adequate time for central review.\n6. Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.\n7. Enrollment timeline: Patients are eligible to enroll on the TarGeT-SCR anytime between diagnosis and the following specific timepoints post completion of RT (if relevant)\n\n   * Patients screening through OPTION #1 are eligible to enroll anytime between diagnosis and 10 days post RT (if completing RT).\n   * Patients screening through OPTIONS #2 or #3 are eligible to enroll anytime between diagnosis and 21 days post RT (if completing RT).\n   * Participants screening for TarGeT-L (lorlatinib) are eligible to enroll on TarGeT-SCR anytime between diagnosis and 31 days post definitive surgery (to allow time for molecular review).\n\nHowever, it is important to note the following:\n\n* For treatment protocols that include targeted therapy administered concurrently with RT, patients must start treatment within 10 calendar days of starting RT.\n* For treatment protocols that only include maintenance\u002Fadjuvant therapy (no systemic therapy given concurrently with radiation), patients must start treatment by 35 days post RT\n\n  #SCREENING OPTIONS\n* OPTION1: Molecular screening through CONNECT TarGeT Clinical Testing Laboratories\n* OPTION2: Molecular screening through a national comprehensive tumor profiling program\n* OPTION3: Clinically validated targeted sequencing or focused profiling\n\nExclusion Criteria:\n\n-Tumors that do not meet HGG and DIPG diagnoses specified above","12 Months","39 Years",{"count":563,"type":21},350,"The goal of this study is to perform genetic sequencing on brain tumors from children, adolescents, and young adult patients who have been newly diagnosed with a high-grade glioma. This molecular profiling will decide if patients are eligible to participate in a subsequent treatment-based clinical trial based on the genetic alterations identified in their tumor.",[152,153,154,28,156,566,567,157,158],"Diffuse Midline Glioma, H3 K27M-Mutant","Metastatic Brain Tumor","2026-06-08",{"date":506,"type":45},{"date":571,"type":45},"2024-08-02",{"date":573,"type":21},"2034-08-28",{"name":169,"class":52},21,{"id":577,"slug":4,"hasResults":11,"nctId":578,"briefTitle":579,"officialTitle":580,"acronym":581,"eligibilityCriteria":582,"healthyVolunteers":11,"sex":17,"minAge":583,"maxAge":146,"enrollmentInfo":584,"targetDuration":4,"studyType":22,"phases":586,"briefSummary":587,"conditions":588,"keywords":596,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":568,"lastUpdatePostDateStruct":598,"startDateStruct":599,"completionDateStruct":601,"leadSponsor":603,"locationsCount":605},"100418695","NCT04732065","ONC206 for Treatment of Newly Diagnosed, Recurrent Diffuse Midline Gliomas, and Other Recurrent Malignant CNS Tumors","Open Label Phase 1 and Target Validation Study of ONC206 in Children and Young Adults With Newly Diagnosed or Recurrent Diffuse Midline Glioma (DMG), and Other Recurrent Primary Malignant Central Nervous System (CNS) Tumors","PNOC023","Inclusion Criteria:\n\n* ARM A: Children and young adults with DMG, H3K27 altered (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who completed at least one line of prior therapy. Prior treatment must have included focal radiation therapy and patients must be within 4-14 weeks from completion of radiation therapy to registration (patients must start treatment within 1 week from registration), have not started any other therapies post-radiation, and have no evidence of disease progression.\n* ARM A: Tumor tissue confirmation of DMG, H3K27 altered is mandatory and pathology must be consistent with a DMG, H3K27 altered.\n* ARM A: Participants must have recovered from all acute side effects of prior therapy.\n* ARM A: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur (these should be discussed with the study team)\n* ARM B: Newly diagnosed children and young adults (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) with a diagnosis of DMG, H3K27 altered are eligible, including spinal cord DMGs.\n* ARM B: Tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG, H3K27 altered.\n* ARM C: Children and young adults with DMGs (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who have evidence of progression but have not been treated for this progression and are recommended to get re-irradiation.\n* ARM C: Patients must have undergone prior focal radiation therapy as part of their initial therapy and should be at least 6 months from prior radiation therapy. If timing is less than 6 months from prior focal radiation, these patients need to be discussed with the study chair(s).\n* ARM C: Tumor tissue confirmation is mandatory and pathology must be consistent with a DMG, H3K27 altered.\n* ARM C: Participants must have recovered from all acute side effects of prior therapy\n* ARM C: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur (these should be discussed with the study team)\n* ARM D: Children and young adults with recurrent primary malignant CNS tumors, excluding DMGs, (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who have evidence of progression but have not been treated for this progression. Participants who received a surgical resection for that progression are eligible if surgery has no curative intent. These patients need to be discussed with the study team.\n* ARM D: Prior tumor tissue confirmation is mandatory and pathology from the primary tumor must be consistent with malignant CNS tumor (diagnosis of ependymoma is allowed).Tissue at the time of progression is not required.\n* ARM D: Participants must have recovered from all acute side effects of prior therapy\n* ARM D: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur (these should be discussed with the study team). Bevacizumab used for pseudoprogression does not require a wash out period.\n* TARGET VALIDATION: Newly diagnosed children and adults (2 years of age and above) with imaging consistent with a DMG, H3K27 altered are eligible.\n* TARGET VALIDATION: Children and young adults with recurrent primary malignant CNS tumors, including recurrent DMG, (2 years of age and above) who have evidence of progression but have not been treated for this progression.\n* TARGET VALIDATION: Participants must undergo tumor tissue collection as part of their standard of care\n* Participants who are receiving steroids must be on a stable or decreasing dose for at least 3 days prior to registration.\n* Peripheral absolute neutrophil count (ANC) \\>= neutrophil 1.0 g\u002Fl.\n* Platelet count \\>= 100 x 10\\^9\u002FL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n* Serum creatinine \\\u003C 1.5 Upper Limit normal (ULN) based on age and gender.\n* Total bilirubin \\\u003C= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin \\\u003C 3 x ULN or direct bilirubin \\\u003C 1.5 x ULN.\n* Alanine aminotransferase (ALT) \\\u003C= 3 x ULN.\n* Aspartate aminotransferase (AST) \\\u003C= 3 x ULN.\n* Patients with seizure disorder may be enrolled if seizure disorder is well controlled\n* The effects of ONC206 on the developing human fetus is unknown. For this reason, females of child-bearing potential and males must agree to use adequate contraception. Adequate methods include: hormonal or barrier method of birth control; or abstinence prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Males treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation\n* Karnofsky \\>= 50 for participants \\> 16 years of age and Lansky \\>= 50 for participants =\\\u003C 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score\n* Participants must be willing to provide adequate tissue. A minimum of 10-20 paraffin embedded unstained slides OR 1 block with tumor content of 40% or greater is required. Frozen tissue is also acceptable. Participants who previously enrolled on PNOC022 and provided adequate tissue, may not need to submit additional tissue - confirm with Study Chairs. Participants who do not meet this criterion may be discussed on a case-by-case basis with the Study Chairs.\n* A legal parent\u002Fguardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate\n* Patients must be enrolled on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution\n\nExclusion Criteria:\n\n* Arm A \\& B: For tumors that do not have a pontine or spinal cord epicenter the following specific exclusion criteria apply: Thalamic DMG and cerebellar, H3K27 altered that has undergone standard radiation without concurrent therapy (other than temozolomide).\n* Arm C \\& D: Patients who participated in trials investigating ONC201 in the upfront setting will not be eligible. Prior ONC201 exposure as part of PNOC022 or expanded access programs will be allowed.\n* Participants who are currently receiving another investigational drug are not eligible.\n* Participants who are currently receiving other anti-cancer agents are not eligible.\n* Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV) or hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible. Note: Participants that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-intravenous (IV) steroids are not necessarily excluded from the study but need to be discussed with the study chair.\n* Participants with uncontrolled infection.\n* Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy.\n* Active illicit drug use or diagnosis of alcoholism.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC206.\n* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant or family.\n* Any participants with illnesses that may affect absorption of ONC206.\n* Any participants on strong inhibitors or inducers of CYP3A4, 2D6, 1A2, 2C9 and 2C19 at least 14 days prior and throughout the study.","2 Years",{"count":585,"type":21},208,[225],"This phase I trial studies the effects and best dose of ONC206 alone or in combination with radiation therapy in treating patients with diffuse midline gliomas that is newly diagnosed or has come back (recurrent) or other recurrent primary malignant CNS tumors. ONC206 is a recently discovered compound that may stop cancer cells from growing. This drug has been shown in laboratory experiments to kill brain tumor cells by causing a so called \"stress response\" in tumor cells. This stress response causes cancer cells to die, but without affecting normal cells. ONC206 alone or in combination with radiation therapy may be effective in treating newly diagnosed or recurrent diffuse midline gliomas and other recurrent primary malignant CNS tumors.",[589,28,590,591,592,593,594,595],"Diffuse Midline Glioma (DMG)","Recurrent Ependymoma","Recurrent Malignant Central Nervous System Neoplasm","Spinal Cord Glioma","World Health Organization (WHO) Grade III Glioma","CNS Tumor","Central Nervous System Tumor",[597],"H3 K27M-Mutant",{"date":464,"type":45},{"date":600,"type":45},"2021-08-23",{"date":602,"type":21},"2027-07-31",{"name":604,"class":52},"Sabine Mueller, MD, PhD",7,{"id":607,"slug":4,"hasResults":11,"nctId":608,"briefTitle":609,"officialTitle":610,"acronym":4,"eligibilityCriteria":611,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":612,"targetDuration":4,"studyType":22,"phases":613,"briefSummary":614,"conditions":615,"keywords":617,"overallStatus":41,"whyStopped":4,"lastUpdateSubmitDate":620,"lastUpdatePostDateStruct":621,"startDateStruct":622,"completionDateStruct":624,"leadSponsor":626,"locationsCount":299},"100628690","NCT07464925","A Phase 1 Safety and Dose Finding Study of GLIX1 in Adults With Recurrent or Progressive High-grade Glioma","An Open-Label Phase 1 Safety and Dose Finding Study of Orally Administered GLIX1 in Adults With Recurrent or Progressive High-grade Glioma","Main Inclusion Criteria:\n\n* Adult patients aged ≥18 years at the time of informed consent\n* Participants must have histologically confirmed Grade 3 or Grade 4 glioma\n* Recurrent or progressive disease\n* A maximum of two prior treatment lines\n* Interval of at least 3 months since the last day off of radiotherapy, unless tumor progression and index lesion is outside the prior radiation field.\n* Interval since last dose of systemic therapy and Baseline MRI of ≥28 days, except:\n\n  * for nitrosoureas (e.g., lomustine, carmustine, fotemustine): 42 days (6 weeks)\n  * for monoclonal antibodies: 42 days (6 weeks)\n  * for small molecules, 4 weeks or at least 5 half-lives (whatever is longer)\n* Recovered from all toxicities from prior treatments to Grade 1 or less by NCI CTCAE v6.0:\n* Participants receiving corticosteroids must be on a stable or decreasing dose of ≤6 mg daily dexamethasone (or ≤40 mg prednisone) for the 7 days prior to the start of study treatment.\n* Participants with seizures must be adequately controlled on a stable regimen of anti-epileptic drugs.\n* Adequate performance status: Eastern Cooperative Oncology Group (ECOG) 0 or 1.\n* Ability to swallow tablets or capsules.\n* Adequate hematological, liver and renal function.\n* Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to first dosing. Women must use a highly effective form of contraception (with Pearl Index \\\u003C1%) for the duration of the study and for at least 3 months after the last dose of study medication.\n* Men with partners of childbearing potential must be willing to use condoms in combination with a second effective method of contraception by the partner during the study and for at least 3 months after the last dose of study medication.\n\nMain Exclusion Criteria:\n\n* Known contraindication for gadolinium (Gd) based, contrast-enhanced MRI\n* Prior history of another invasive malignancy unless a complete remission was achieved at least 3 years prior to enrolment AND no additional therapy is required during the study period, except for anti-estrogen or androgen therapy and\u002For bisphosphonates or denosumab.\n* Participants with known active or uncontrolled infection, and\u002For unexplained fever \\>38°C in the 3 days prior to the start of study treatment.\n* Major non-tumor related surgical procedure or significant traumatic injury within 28 days prior to signing of consent.\n* Receiving any investigational products (defined as treatment for which there is currently no regulatory authority-approved indication) within 4 weeks or 5 half-lives (whichever is the longest) prior to Baseline MRI.",{"count":90,"type":21},[225],"This is an open-label, multicenter dose-escalation study to be followed by a dose expansion to define the optimal dose of GLIX1 as monotherapy by reviewing safety and tolerability, disease characteristics and pharmacokinetic profiles and preliminary clinical activity in participants with a high grade diffuse glioma that progressed during or recurred after prior standard of care therapies or investigational therapies as clinically indicated.\n\nPatients will be treated daily with GLIX1 capsules until disease progression or unacceptable safety.",[616,438,28],"Glioblastoma Multiforme of Brain",[618,438,67,28,619],"GLIX1","TET2","2026-06-07",{"date":504,"type":45},{"date":623,"type":45},"2026-04-20",{"date":625,"type":21},"2027-12",{"name":627,"class":82},"Tetragon Biosciences Ltd",""]