[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"metastatic-breast-cancer\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:metastatic-breast-cancer":639},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,172,0,25,[9,41,66,87,106,130,154,174,203,228,249,274,305,352,379,399,419,440,463,483,502,538,556,589,611],{"id":10,"slug":4,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":4,"eligibilityCriteria":14,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":17,"targetDuration":4,"studyType":20,"phases":21,"briefSummary":23,"conditions":24,"keywords":26,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":29,"lastUpdatePostDateStruct":30,"startDateStruct":33,"completionDateStruct":35,"leadSponsor":37,"locationsCount":40},"100053487",false,"NCT07624617","Fast-Her: Fasting Effects on Breast Cancer Treatment","Inclusion Criteria:\n\n* Age ≥18 years\n* Histologically confirmed metastatic breast cancer\n* Menopausal or medically ovarian suppressed\n* Currently receiving capivasertib therapy (2 tablets twice daily, 4 days per week)\n* Stable on current capivasertib regimen for at least 2 weeks\n* an ECOG performance status of 0-1\n* BMI ≥25kg\u002Fm2\n* Able to provide informed consent\n* Willing to comply with study procedures including CGM wear, food tracking by mCC app and dietary modifications\n* Access to smartphone or tablet for mobile application use\n\nExclusion Criteria:\n\n* Type 1 diabetes mellitus\n* Uncontrolled type 2 diabetes (HbA1c \\>9.0%)\n* History of severe hypoglycemia\n* Eating disorders or contraindications to fasting\n* Pregnancy or breastfeeding\n* Significant gastrointestinal disorders affecting food absorption\n* Unable to fast for medical reasons\n* Concurrent participation in other dietary intervention studies\n* A history of significantly abnormal lab results within 4 weeks of consent date, such as hematologic (Hgb \\\u003C 10.0, platelets \\\u003C 100), hepatic (LFTs \\> 2X nl), renal (Cr \\> 1.5)","ALL","18 Years",{"count":18,"type":19},15,"ESTIMATED","INTERVENTIONAL",[22],"NA","We hypothesize that promoting a fasting state will strengthen the anti-cancer effects of PI3K inhibitors in metastatic breast cancer (MBC) treatment. The primary objective of this study is to assess acceptability of prolonged fasting in this population.",[25],"Metastatic Breast Cancer",[27],"capivasertib","RECRUITING","2026-07-09",{"date":31,"type":32},"2026-07-13","ACTUAL",{"date":34,"type":32},"2026-05-18",{"date":36,"type":19},"2027-07-01",{"name":38,"class":39},"University of Minnesota","OTHER",1,{"id":42,"slug":4,"hasResults":11,"nctId":43,"briefTitle":44,"officialTitle":45,"acronym":4,"eligibilityCriteria":46,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":47,"targetDuration":4,"studyType":20,"phases":49,"briefSummary":51,"conditions":52,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":56,"lastUpdatePostDateStruct":57,"startDateStruct":59,"completionDateStruct":61,"leadSponsor":63,"locationsCount":65},"100520894","NCT06062498","Elacestrant vs Elacestrant Plus a CDK4\u002F6 Inhibitor in Patients With ERpositive\u002FHER2-negative Advanced or Metastatic Breast Cancer","Randomized Phase II Study of Elacestrant vs Elacestrant Plus a CDK4\u002F6 Inhibitor (Palbociclib, Abemaciclib, or Ribociclib) in Patients With ER+\u002FHER2- Advanced or Metastatic Breast Cancer With Prior Exposure to a CKD4\u002F6 Inhibitor","Inclusion Criteria All Arms:\n\n* Patients must have histologically or cytologically confirmed ER-positive and HER2- negative breast cancer as per the American Society of Clinical Oncology (ASCO)\u002FCollege of American Pathologists (CAP) guidelines (Allison et al, 2020, Wolff et al, 2018).\n\nNote: In the context of this trial, ER status will be considered positive if \\>10% of tumor cells demonstrate positive nuclear staining by immunohistochemistry. Note: Fresh biopsy is not a requirement.\n\n* Patients must have a confirmed ESR1 mutation. Note: This information will be drawn from patients' treatment charts. Mutational analysis will be done as standard of care; there is no research-related mutational testing for this study. ctDNA may be used for mutational testing.\n* Patients must have at least one measurable lesion (as per RECIST v1.1) lesion anywhere in the body or a mainly lytic metastatic bone lesion. Note: Lytic bone lesions with identifiable soft tissue components that can be evaluated by cross-sectional imaging techniques such as CT or MRI can be considered as measurable lesions if the soft tissue component meets the definition of measurability per RECIST v1.1.\n* Patients must have received at least 2 prior endocrine therapies, including a CDK4\u002F6 inhibitor in the metastatic disease setting.\n* Patients must be age ≥ 18 years. Patients of childbearing potential (POCBP) may be premenopausal, postmenopausal, or perimenopausal.\n* Potential POCBP who may be menopausal and are \\\u003C 55 years of age must have a serum follicle-stimulating hormone (FSH) level \\> 40 mIU\u002FmL to confirm menopause.\n* Patients must exhibit an ECOG performance status of 0 or 1.\n* Patients must have adequate organ and bone marrow function as defined below:\n\nLeukocytes (WBC) ≥ 3,000\u002FmcL Absolute neutrophil count (ANC) ≥ 1,500\u002FmcL Hemoglobin (Hgb) ≥ 80-100 g\u002FdL Platelets (PLT) ≥ 50,000\u002FmcL Total serum bilirubin \\\u003C 1.5 x Institutional upper limit of normal (ULN) AST (SGOT) ≤ 3 x institutional ULN (no liver metastases)\n\n* 5 x institutional ULN (liver metastases present) ALT (SGPT) ≤ 3 x institutional ULN\n* 5 x institutional ULN (liver metastases present) Cockcroft-Gault based creatinine clearance\n\n  * 50 mL\u002Fmin\n\nNote:\n\n* Creatinine clearance (DMAB)\n\n  = (\\[140-age in years\\] × weight in kg)\u002F (\\[serum creatinine in mg\u002FdL\\] × 72)\n* Creatinine clearance (DFAB) = (0.85 × \\[140-age in years\\] × weight in kg)\u002F (\\[serum creatinine in mg\u002FdL\\] × 72) Note: Growth factor\u002Ftransfusion support to attain these levels is not permitted.\n\n  * For patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration.\n  * For patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.\n  * Patients with a known 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  * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are eligible.\n  * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. Elacestrant is a known teratogen. For this reason, patients of child-bearing potential (POCBP) and their partners with sperm-producing reproductive capacity must agree to use adequate contraception (see Appendix B) from time of informed consent, for the duration of study participation, and for 7 days following completion of elacestrant therapy.\n\nShould a POCBP become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately. Patients with sperm-producing reproductive capacity (PWSPRC) treated or enrolled on this protocol must also agree to use adequate contraception with partners of childbearing potential from time of informed consent, for the duration of study participation, and 7 days after completion of administration. Note: A POCBP is any patient (regardless of gender, sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) with an egg-producing reproductive tract who meets the following criteria:\n\n* Has not undergone a hysterectomy or bilateral oophorectomy\n* Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \\> 12 months) Note: POCBP who are on combination therapy with any study CKD4\u002F6 inhibitor (palbociclib, abemaciclib, or ribociclib) must agree to use adequate contraception from time of informed consent, for the duration of study participation, and for 21 days following completion of CKD4\u002F6 inhibitor therapy. POCBP must have a negative pregnancy test prior to registration on study. If initial urine pregnancy test is positive or cannot be confirmed negative, serum pregnancy test will be required. -Patients must have the ability to understand and the willingness to sign a written informed consent document.\n\nInclusion Criteria - Combination Therapy Arm 2 with Palbociclib, Abemaciclib, or Ribociclib\n\n-Patients who have been treated with one or two prior hormonal therapies in the metastatic setting if at least one hormonal therapy was in combination with a CDK4\u002F6 inhibitor.\n\nNotes:\n\n* Patients who are already on or have already been exposed to one or two of the study CDK4\u002F6 inhibitors at registration will be assigned a different study CDK4\u002F6 inhibitor (e.g., if a patient has already been exposed to abemaciclib, they will be given ribociclib or palbociclib; similarly, if a patient has already been exposed to palbociclib and abemaciclib, they will be given ribociclib.)\n* One-to-one randomization will be done by the QA team once patients have been registered.\n\nExclusion Criteria All Arms:\n\n* Patients who have received prior elacestrant.\n* Patients who have had chemotherapy or radiotherapy ≤ 28 days (6 weeks for nitrosureas or mitomycin C) prior to registration.\n* Patients who have taken steroid therapy or any other immunosuppressive therapy within 7 days of first dose prior to trial treatment.\n* Patients with brain metastases. Note: Patients with stable brain or subdural metastases are allowed if the patient has completed local therapy and was on a stable or decreasing dose of corticosteroids at baseline for brain management for at least 4 weeks before starting treatment in this study. The dose must be \\\u003C2.0 mg\u002Fday of dexamethasone or equivalent. Any signs (e.g., radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment. RANO criteria are used to evaluate brain metastases\n* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \\> Grade 3) with the exception of alopecia.\n* Patients who are receiving any other investigational agents. For patients who were previously on palbociclib, abemaciclib, or ribociclib, the washout period between stopping that CDK4\u002F6 inhibitor and starting a different one is 14 days.\n* Patients with advanced, symptomatic visceral spread who are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or liver involvement \\>50%.\n* Patients with documented pneumonitis\u002Finterstitial lung disease prior to registration.\n* Patients who have received major surgery within 28 days before starting trial therapy.\n* Patients who are taking strong or moderate CYP3A4 inducers or strong or moderate CYP3A4 inhibitors. See Section 4.4 for additional incompatibilities.\n* Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to elacestrant. Note: Refer to exclusion criteria below for eligibility criteria related to study CDK4\u002F6 inhibitors.\n* Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following:\n\n  * Hypertension that is not controlled on medication\n  * Psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n  * Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints\n* Patients with refractory or chronic nausea, gastrointestinal conditions (including significant gastric or bowel resection or gastric bypass surgery), history of malabsorption syndrome, or any other uncontrolled gastrointestinal condition that impact the absorption of the study drug. Similarly, patients who are unable to take\u002Fretain oral medications.",{"count":48,"type":19},174,[50],"PHASE2","Breast cancer is not only the leading cause of cancer in women, but also the leading cause of cancer deaths in women. Estrogen receptor-positive and HER2-negative breast cancer is the most prevalent breast cancer subtype. Endocrine therapy is the mainstay of treatment; however, due to the varied nature of the disease, development of resistance to this therapeutic approach is very common in the metastatic setting.\n\nThe purpose of this study is to see whether the effectiveness of elacestrant can be enhanced by combining it with a targeted agent such as a CDK4\u002F6 inhibitor to treat patients with ER+\u002FHER2- or metastatic breast cancer with prior exposure to a CDK4\u002F6 inhibitor.",[53,54,55,25],"Estrogen-receptor-positive Breast Cancer","HER2\u002FNeu-Negative Breast Cancer","Advanced Breast Cancerv","2026-06-30",{"date":58,"type":32},"2026-07-02",{"date":60,"type":32},"2023-09-29",{"date":62,"type":19},"2029-07-01",{"name":64,"class":39},"Northwestern University",3,{"id":67,"slug":4,"hasResults":11,"nctId":68,"briefTitle":69,"officialTitle":70,"acronym":4,"eligibilityCriteria":71,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":72,"targetDuration":74,"studyType":75,"phases":4,"briefSummary":76,"conditions":77,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":56,"lastUpdatePostDateStruct":79,"startDateStruct":80,"completionDateStruct":82,"leadSponsor":84,"locationsCount":86},"100513364","NCT05964504","Improving Survival for Metastatic Lobular Breast Cancer (PLUMB Registry)","Improving Survival for Those With Metastatic Lobular Breast Cancer Through Development of the Multi-center PLUMB Registry-a Prospective Study of LobUlar Metastatic Breast Cancer","Inclusion Criteria:\n\n1. Histologically confirmed invasive lobular carcinoma. Mixed lobular\u002Fductal cancer is allowed.\n2. Age \\>=18 years\n3. Any receptor subtype.\n4. Ability to understand a written informed consent document, and the willingness to sign it.\n\nExclusion Criteria:\n\n1. Stage I-III breast cancer.\n2. Lack of lobular histology on tumor biopsy.\n3. Other active cancer (prior treated cancer with no current evidence of disease is allowed).",{"count":73,"type":19},12,"10 Years","OBSERVATIONAL","This is a prospective observational registry for patients with invasive lobular carcinoma (ILC) of the breast. After the first 1cohort is enrolled, the collected data will be utilized to develop an ILC specific response assessment tool.",[25,78],"Lobular Breast Carcinoma",{"date":58,"type":32},{"date":81,"type":32},"2023-12-20",{"date":83,"type":19},"2036-02-28",{"name":85,"class":39},"University of California, San Francisco",4,{"id":88,"slug":4,"hasResults":11,"nctId":89,"briefTitle":90,"officialTitle":91,"acronym":4,"eligibilityCriteria":92,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":93,"targetDuration":4,"studyType":20,"phases":95,"briefSummary":96,"conditions":97,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":56,"lastUpdatePostDateStruct":99,"startDateStruct":100,"completionDateStruct":102,"leadSponsor":104,"locationsCount":65},"100241546","NCT02422641","Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis","Traditional Incision and Drainage of Cutaneous Abscess Vs. Minimally Invasive Incision and Drainage With Vessel Loop: A Randomized Controlled Trail","Inclusion Criteria\n\n* Adults (male and female) age \\>18\n* Eastern Cooperative Group (ECOG) Performance Scale 0-1 (see Appendix I)\n* Histologically or cytologically confirmed invasive breast cancer of the following subtype:\n* TRIPLE NEGATIVE (ER-negative, PR-negative, and HER2-negative disease). Triple-negative patients will be defined per ASCO-CAP Guidelines.\n* HER2-POSITIVE: HER2-positive patients will be defined per ASCO-CAP Guidelines.\n* HORMONE REFRACTORY: Patients with ER\u002FPR-positive disease according to ASCO-CAP guidelines above may be considered if they have disease progression after two lines of hormonal therapy (administered in the adjuvant or metastatic setting), or are deemed clinically hormone-resistant taking into consideration the rate of progression of disease or a short interval of time on first line hormonal therapy before progression. Clinically hormone-resistant patients MUST also be discussed with the Study Chair, Study co-chair or designee in advance for approval.\n\nNOTE: ASCO-CAP guidelines state that ER and PR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. HER2-positive is defined as HER2 IHC 3+, ISH ≥ 2.0, or average HER2 copy number ≥ 6.0 signals.\n\nNOTE: A patient who has a change in receptor status (e.g. PR negative to positive) may be stratified as triple negative or hormone positive, contrary to the most recent receptor testing, for the purposes of the study, based upon the clinical course at the discretion of the Study Chair, Study co-chair, or designee in advance for approval.\n\n* Cytologic or unequivocal radiographic confirmation of leptomeningeal metastasis by dural puncture and\u002For neuroimaging with or without known brain metastasis\n* Adequate organ function as follows:\n\nEstimated creatinine clearance \\>70 cc\u002Fmin (calculated by Cockcroft-Gault formula) White blood cell counts \\>3000 cells\u002FmcL Absolute neutrophil count \\>1500 cells\u002FmcL Platelet count \\>100,000 cells\u002FmcL Hematocrit \\>30% Serum bilirubin \\\u003C1.5 x the ULN or \\\u003C5x the ULN if secondary to liver metastasis Alanine aminotransferase or aspartate aminotransferase \\\u003C2.5x the ULN or \\\u003C5x the ULN if secondary to liver metastasis Alkaline phosphatase \\\u003C2.5x the ULN or \\\u003C5x the ULN if secondary to liver metastasis\n\n\\- Able to provide confirmed consent\n\nExclusion Criteria\n\n* Prior allergy or adverse reaction to methotrexate\n* New York Heart Association Heart Failure Class \\>3\n* Active diabetes insipidus\n* Active mucositis\n* Chemotherapy or stereotactic radiotherapy within the last 2 weeks\n* Partial brain radiotherapy (i.e. \\\u003C40% of total brain volume) within the last 2 weeks\n* Whole brain radiotherapy within the last 6 months or partial brain radiotherapy exceeding \\>40% of total brain volume within the last 6 months\n* Prior treatment with any methotrexate containing systemic regimen within 1 year (excluding intrathecal methotrexate)\n* Concurrent or planned systemic chemotherapy, radiotherapy, new hormonal or anti- HER2 directed therapy directed at management of breast cancer (existing anti-HER2 therapy can be continued as recently recommended in the National Consensus Guidelines (26)\n* Uncontrolled or progressive systemic disease or other concurrent condition which in the Investigator's opinion makes HD-MTX an undesirable treatment option for the patient or would jeopardize compliance\n* Contraindication to MRI\n* Use of salicylates, non-steroidal anti-inflammatory drugs, or sulfonamide medications within one week of start of methotrexate\n* Pregnant women or women who are breastfeeding.\n* Patients with significant visceral fluid collections including ascites, pericardial effusions, pleural effusions or others may experience delayed clearance of methotrexate because of third space accumulation which could result in methotrexate toxicity and inability to tolerate the proposed study treatment. While these are not absolute exclusions the Study Chair or co-Chairs should be contacted to discuss possible enrollment. Patients with significant ascites defined as European Association for the Study of the Liver \\> grade 2 (Appendix IV), or with asymptomatic pleural effusions with an estimated size \\>200 mL, or with symptomatic pleural effusion of any size will be excluded.\n\nNOTE: Systemic staging of the chest\u002Fabdomen\u002Fpelvis is required for study entry. See Sections 8.1.9. Body fluid will be assessed based on this study.",{"count":94,"type":19},16,[50],"This study is a prospective evaluation of systemic, intravenous high-dose methotrexate (HD-MTX, 8 g\u002Fm2) in patients with triple negative, HER2-positive, and hormone refractory breast cancer with leptomeningeal metastasis (LMD) with or without brain parenchymal involvement.",[25,98],"Leptomeningeal Disease",{"date":58,"type":32},{"date":101,"type":4},"2015-05",{"date":103,"type":19},"2027-07",{"name":105,"class":39},"Wake Forest University Health Sciences",{"id":107,"slug":4,"hasResults":11,"nctId":108,"briefTitle":109,"officialTitle":110,"acronym":111,"eligibilityCriteria":112,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":113,"enrollmentInfo":114,"targetDuration":4,"studyType":75,"phases":4,"briefSummary":116,"conditions":117,"keywords":118,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":120,"lastUpdatePostDateStruct":121,"startDateStruct":122,"completionDateStruct":124,"leadSponsor":126,"locationsCount":129},"100548192","NCT06417801","Minimally Interventional Study on Prevalence of Emerging ESR1 Mutations in Liquid Biopsy in Three Cohorts of Patients With Breast Cancer in Comparison With Patient's Baseline ESR1 Mutation Status as Defined by Tissue Profiling.","Minimally Interventional Study on Prevalence of Emerging ESR1 Mutations in Liquid Biopsy in Three Cohorts of Patients With Breast Cancer, With and Without Prior Therapies inMetastatic Setting, and During First-line Aromatase InhibitorPlus CDK4\u002F6 Inhibitor Therapy, in Comparison With Patient's Baseline ESR1 Mutation Status as Defined by Tissue Profiling.","Pangeia-2","Inclusion Criteria:\n\nCohort 1:\n\n* BC patients, male and female,\n* 18 years old and older,\n* Pre or post menopausal,\n* With HR+ (ER and\u002For PR positive) and Her-2 negative (confirmed centrally),\n* Locally advanced irresectable and\u002For metastatic disease\n* Confirmation of HR and Her-2 status may be performed in the primary tumor or in the metastatic lesion (patients with discordant results may be included),\n* Patients must be candidates to CDK4\u002F6i therapy in combination with endocrine therapy in the first line setting (with or without ovarian suppression)\n* Patients may have received one previous line of chemotherapy in the metastatic setting, but no endocrine therapy in the metastatic setting is allowed,\n* Patients may have received chemotherapy in the neo\u002Fadjuvant setting,\n* Patients may have received endocrine therapy (with or without ovarian suppression) in the neo\u002Fadjuvant setting,\n* Patients may have received a CDK4\u002F6i in the adjuvant setting, provided they are still candidates for CDK4\u002F6i therapy in the metastatic setting,\n* Patients must be able to undergo a liquid biopsy procedure before starting their first line treatment,\n* All patients must fill and sign an informed consent form.\n\nCohort 2:\n\n* BC patients,\n* Male and female,\n* 18 years old and older,\n* pre or post menopausal,\n* With HR+ (ER and\u002For PR positive) and Her-2 negative (confirmed centrally),\n* Locally advanced irresectable and\u002For metastatic disease who have progressed on a CDK4\u002F6i in combination with endocrine therapy (with or without ovarian suppression) in the first or second line setting,\n* All other non-conflicting inclusion criteria for cohort 1 apply.\n\nCohort 3:\n\n* BC Patients,\n* Male and female,\n* 18 years or older,\n* pre- or post-menopausal,\n* With HR+ (ER and\u002For PR positive), HER2-negative (centrally confirmed) locally advanced unresectable and\u002For metastatic disease,\n* Confirmation of HR and HER2 status may be performed on the primary tumour or the metastatic lesion (patients with discordant results may be included),\n* Patients must be on first-line hormonal therapy with an aromatase inhibitor plus a CDK4\u002F6 inhibitor (with or without ovarian suppression) for at least 6 months,\n* No clinical or radiological evidence of progressive disease,\n* Patients may have received a prior line of chemotherapy in the metastatic setting; however, prior endocrine therapy in the metastatic setting is not permitted,\n* Patients may have received chemotherapy in the neoadjuvant\u002Fadjuvant setting,\n* Patients may have received endocrine therapy (with or without ovarian suppression) in the neoadjuvant\u002Fadjuvant setting,\n* Patients may have received a CDK4\u002F6 inhibitor in the adjuvant setting, provided they are still eligible for CDK4\u002F6 inhibitor therapy in the metastatic setting,\n* Patients must be able to undergo a liquid biopsy procedure before starting their first-line treatment,\n* All patients must read and sign an Informed Consent Form.\n\nExclusion Criteria:\n\n* Patients WITHOUT HR+ (ER- and\u002For PR-positive)\u002FHER2-negative disease,\n* Patients without radiological and\u002For pathological confirmation of locally unresectable and\u002For metastatic breast cancer,\n* Patients who are NOT candidates for further systemic treatment following a diagnosis of metastatic disease or disease progression,\n* Patients who have already started a CDK4\u002F6 inhibitor in combination with endocrine therapy (with or without ovarian suppression) for first-line metastatic disease (for Cohort 1);\n* Patients who have already started a new line of treatment for metastatic disease following progression on a CDK4\u002F6 inhibitor in combination with endocrine therapy (with or without ovarian suppression) (for Cohort 2);\n* Patients with any suspicion of clinical or radiological disease progression at the time of the first liquid biopsy collection (for Cohort 3),\n* Patients who are NOT able to undergo a liquid biopsy procedure,\n* Patients who are NOT able to provide informed consent.","100 Years",{"count":115,"type":19},170,"Minimally interventional study on prevalence of emerging ESR1 mutations in liquid biopsy in three cohorts of patients with breast cancer (with and without prior therapies in metastatic setting, and during first-line aromatase inhibitor plus CDK4\u002F6 inhibitor therapy) in comparison with patient's baseline ESR1 mutation status as defined by tissue profiling.",[25],[119],"Breast Cancer; ER-positive; ESR-1 mutation","2026-06-26",{"date":56,"type":32},{"date":123,"type":32},"2024-06-17",{"date":125,"type":19},"2027-12-30",{"name":127,"class":128},"AstraZeneca","INDUSTRY",6,{"id":131,"slug":4,"hasResults":11,"nctId":132,"briefTitle":133,"officialTitle":134,"acronym":4,"eligibilityCriteria":135,"healthyVolunteers":11,"sex":15,"minAge":136,"maxAge":4,"enrollmentInfo":137,"targetDuration":4,"studyType":20,"phases":139,"briefSummary":141,"conditions":142,"keywords":143,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":120,"lastUpdatePostDateStruct":145,"startDateStruct":147,"completionDateStruct":149,"leadSponsor":151,"locationsCount":153},"100545127","NCT06377852","The CDK4\u002F6 Inhibitor Dosing Knowledge (CDK) Study","Comparing Oral Drug Dosing Strategies in Older Patients With Metastatic Breast Cancer to Maximize Tolerance and Reduce Discontinuation: The CDK4\u002F6 Inhibitor Dosing Knowledge (CDK) Study","Inclusion Criteria:\n\n1. Hormone receptor positive (HR+) HER2 negative metastatic breast cancer. Cut-off values for positive\u002Fnegative staining should be as per standard practice in accordance with ASCO\u002FCAP (American Society of Clinical Oncology\u002FCollege of American Pathologists) guidelines. Verification of histology is preferred at the time of recurrence and where not possible or necessary in the judgment of the treating physician, the study will accept histology from the initial diagnosis.\n2. Candidate for planned endocrine therapy in combination with 1st use of palbociclib or ribociclib, in the metastatic setting. The planned endocrine partner can be an aromatase inhibitor (letrozole, anastrozole, exemestane) or fulvestrant, selected through patient\u002Fprovider choice.\n3. Aged 65 years or older\n4. Adequate bone marrow and organ function. Laboratory values must be within normal institutional limits, or within ranges as indicated below, or demonstrate minor abnormalities that are deemed clinically non-significant by the investigator.\n\n   * Absolute neutrophil count ≥ 1,000\u002FµL\n   * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (participants with documented Gilbert's disease are allowed total bilirubin up to 5X ULN)\n   * AST (SGOT)\u002FALT (SGPT) \\\u003C3 x institutional ULN, or ≤ 5 x ULN for subjects with documented metastatic disease to the liver.\n5. Baseline QTc ≤ 480 ms (only for ribociclib patients)\n6. Ability to understand and the willingness to provide informed consent. Note: Remote consent is allowed per institutional guidelines.\n\nExclusion Criteria:\n\n1. Previous treatment with a CDK4\u002F6 inhibitor for metastatic breast cancer, or previous treatment within the past 12 months with a CDK4\u002F6 inhibitor in the neo\u002Fadjuvant breast cancer setting.\n2. Received greater than 30 days (in the metastatic setting) of the specific endocrine therapy agent planned as partner to the CDK4\u002F6 inhibitor in the study at the time of randomization.\n3. Known history of intolerance or allergy to the planned agents used in this trial.\n4. Uncontrolled intercurrent illness that, as evaluated by the treating clinician, would hinder compliance with study requirements.\n5. Concurrent therapy with other investigational agents.\n6. Rapidly progressive brain metastases.\n7. Active or chronic Hepatitis B or C are eligible provided they meet liver function laboratory criteria and are not on medication with a known interaction with the study agents.\n8. Current use of drugs that have known potential to prolong the QT interval (e.g., antiarrhythmic drugs), for patients on ribociclib. Note: If concomitant use cannot be avoided, monitor ECG when initiating, during concomitant use, and as clinically indicated. Refer to crediblemeds.org as a resource.\n9. Prior or concurrent malignancies that are undergoing active treatment.","65 Years",{"count":138,"type":19},500,[140],"PHASE3","The purpose of this study is to generate evidence on an alternative dosing strategy for CDK4\u002F6 inhibitors to help more patients with Metastatic Breast Cancer (MBC) (age ≥ 65 years) tolerate side effects and stay on treatment longer, to derive the most clinical benefit from these drugs.\n\nThe primary objective of the CDK Study is to compare time to treatment discontinuation (TTD) on the approved dosing for palbociclib (125 mg orally daily on days 1-21 of 28-day cycle) or ribociclib (600 mg orally daily on days 1-21 of 28-day cycle) vs. TTD using titrated dosing approach with the same schedule but starting at a lower dose of palbociclib (100 mg or 75 mg) or ribociclib (400 mg or 200 mg) and escalating the dose if well-tolerated in combination with provider\u002Fpatient choice endocrine therapy (aromatase inhibitor (AI) or fulvestrant) in patients age 65 or older with HR+\u002FHER2- MBC. The secondary and exploratory objectives will generate evidence needed to personalize treatment decisions by comparing patient-centric secondary outcomes and evaluating baseline factors.\n\nTogether with their treating physician, participants will choose the CDK4\u002F6 inhibitor (palbociclib or ribociclib) and which endocrine therapy (aromatase inhibitor or fulvestrant) of their choice but will be randomized to either Arm 1 (indicated dosing) or Arm 2 (titrated dosing).\n\nNote: Telehealth visits are allowed at any time per institutional guidelines. In addition, the study allows for remote consenting per institutional guidelines.",[25],[144],"MBC",{"date":146,"type":32},"2026-06-29",{"date":148,"type":32},"2024-10-29",{"date":150,"type":19},"2028-09-01",{"name":152,"class":39},"American Society of Clinical Oncology",73,{"id":155,"slug":4,"hasResults":11,"nctId":156,"briefTitle":157,"officialTitle":158,"acronym":159,"eligibilityCriteria":160,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":161,"targetDuration":4,"studyType":20,"phases":163,"briefSummary":164,"conditions":165,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":120,"lastUpdatePostDateStruct":166,"startDateStruct":167,"completionDateStruct":169,"leadSponsor":171,"locationsCount":173},"100507964","NCT05894239","A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer","A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo As Maintenance Therapy After First Line Induction Therapy in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer","INAVO122","Inclusion Criteria:\n\n* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1\n* Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection\n* Confirmation of HER2 biomarker eligibility based on valid results from central testing of tumor tissue documenting HER2-positivity\n* Confirmation of PIK3CA-mutation biomarker eligibility based on valid results from central testing of tumor tissue documenting PIK3CA-mutated tumor status\n* Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of \\>= 6 months\n* LVEF (left ventricular ejection fraction) of at least 50% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)\n* Adequate hematologic and organ function prior to initiation of study treatment\n\nExclusion Criteria:\n\n* Prior treatment in the locally advanced or metastatic setting with any PI3K, AKT, or mTOR inhibitor or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway\n* Any prior systemic non-hormonal anti-cancer therapy for locally advanced or metastatic HER2-positive breast cancer prior to initiation of induction therapy\n* History or active inflammatory bowel disease\n* Disease progression within 6 months of receiving any HER2-targeted therapy\n* Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes\n* Participants with active HBV infection\n* Clinically significant and active liver disease, including severe liver impairment, viral or other hepatitis, current alcohol abuse, or cirrhosis\n* Symptomatic active lung disease, including pneumonitis or interstitial lung disease\n* Any history of leptomeningeal disease or carcinomatous meningitis\n* Serious infection requiring IV antibiotics within 7 days prior to Day 1 of Cycle 1\n* Any concurrent ocular or intraocular condition that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition\n* Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye",{"count":162,"type":19},230,[140],"This study will evaluate the efficacy and safety of inavolisib in combination with Phesgo (pertuzumab, trastuzumab, and rHuPH20 injection for subcutaneous use) compared with placebo in combination with Phesgo, as maintenance therapy, after induction therapy in participants with previously untreated HER2-positive advanced breast cancer (ABC).",[25],{"date":146,"type":32},{"date":168,"type":32},"2023-09-08",{"date":170,"type":19},"2032-12-28",{"name":172,"class":128},"Hoffmann-La Roche",192,{"id":175,"slug":4,"hasResults":11,"nctId":176,"briefTitle":177,"officialTitle":177,"acronym":178,"eligibilityCriteria":179,"healthyVolunteers":11,"sex":180,"minAge":16,"maxAge":4,"enrollmentInfo":181,"targetDuration":4,"studyType":20,"phases":183,"briefSummary":184,"conditions":185,"keywords":186,"overallStatus":194,"whyStopped":4,"lastUpdateSubmitDate":195,"lastUpdatePostDateStruct":196,"startDateStruct":197,"completionDateStruct":199,"leadSponsor":201,"locationsCount":40},"100645033","NCT07676344","CRYO-TOUCH: Cryoablation of the Primary Breast Tumor in Metastatic Breast Cancer","CRYO-TOUCH","Inclusion Criteria:\n\n* Female aged ≥18 years.\n* Histologically confirmed metastatic breast carcinoma, regardless of histological subtype, hormone receptor status, HER2 status, or tumor grade.\n* Receiving systemic anticancer treatment for metastatic breast cancer, including chemotherapy, immunotherapy, endocrine therapy, targeted therapy, or combination regimens.\n* Clinical response or stable disease according to RECIST v1.1 on the most recent imaging assessment performed within 3 months before enrollment, except for the primary breast lesion, which may be progressing.\n* Eligible for cryoablation of the primary breast tumor:\n* ECOG Performance Status ≤2.\n* Effective contraception for women of childbearing potential.\n* Able and willing to provide written informed consent.\n\nExclusion Criteria:\n\n* Contraindication to cryoablation according to the investigator and\u002For interventional radiologist.\n* Contraindication to gadolinium-enhanced breast MRI according to institutional practice and radiologist assessment.\n* Pregnant or breastfeeding women.\n* Participation in another interventional clinical study with an ongoing exclusion period or that could interfere with the present study according to investigator judgment.\n* Psychiatric disorder or any medical condition that, in the opinion of the investigator, could compromise study participation or compliance with study procedures.\n* Adults under legal protection or unable to provide informed consent.\n* Persons deprived of liberty by judicial or administrative decision.\n* Absence of health insurance coverage.","FEMALE",{"count":182,"type":19},42,[22],"Metastatic breast cancer remains an incurable disease for most patients. While surgical treatment of the primary breast tumor is commonly performed in localized breast cancer, its role in metastatic breast cancer remains controversial due to the lack of demonstrated survival benefit and the potential interruption of systemic anticancer therapies.\n\nCryoablation is a minimally invasive outpatient procedure that destroys tumor tissue through controlled freezing. In localized breast cancer, cryoablation has shown promising results regarding local tumor control, safety, and patient quality of life. However, evidence regarding its use in metastatic breast cancer remains limited.The primary objective of this prospective single-center cohort study is to evaluate local tumor control 12 months after cryoablation of the primary breast tumor in patients with metastatic breast cancer.",[25],[25,187,188,189,190,191,192,193],"Cryoablation","Interventional Radiology","Local Tumor Control","Quality of Life","Implementation Science","Breast-Q","Minimally Invasive Therapy","NOT_YET_RECRUITING","2026-06-24",{"date":56,"type":32},{"date":198,"type":19},"2026-10-01",{"date":200,"type":19},"2030-01-01",{"name":202,"class":39},"Hospices Civils de Lyon",{"id":204,"slug":4,"hasResults":11,"nctId":205,"briefTitle":206,"officialTitle":207,"acronym":4,"eligibilityCriteria":208,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":209,"targetDuration":4,"studyType":75,"phases":4,"briefSummary":211,"conditions":212,"keywords":216,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":195,"lastUpdatePostDateStruct":220,"startDateStruct":221,"completionDateStruct":223,"leadSponsor":225,"locationsCount":227},"100511921","NCT05945732","DESTINY Breast Respond HER2-(Ultra)Low Europe","A Prospective, Non-interventional Study (NIS) With Trastuzumab Deruxtecan For Patients With HER2-(Ultra)Low Expressing Unresectable and\u002For Metastatic Breast Cancer Accompanied By a Disease Registry of Patients Treated With Conventional Chemotherapy (DESTINY Breast Respond HER2-(Ultra)Low Europe)","Inclusion Criteria:\n\nStudy Group 1 and Study Group 2\n\n* Adult patient (age ≥ 18 years) with histological or cytological confirmed diagnosis of unresectable and\u002For mBC\n* Decision to newly initiate therapy of T-DXd or conventional chemotherapy according to the physicians choice per SmPC\n* Written and signed Informed Consent to participate in the study\n\nStudy Group 1\n\n* Documented HER2-low status (IHC1+, IHC2+\u002FISH-)\n* Patients who have received prior chemotherapy in the metastatic setting or\n* Patients who have developed disease recurrence during or within 6 months of completing adjuvant chemotherapy\n\nStudy Group 2:\n\n* Documented HR+ status\n* Documented HER2-low status (IHC1+ or IHC2+\u002FISH-) or HER2-ultralow (defined as IHC 0 with membrane staining \\[IHC \\> 0 to \\\u003C1+\\]) status\n* Patients who have received at least one endocrine therapy in the metastatic setting\n* Patients who have NOT received prior chemotherapy in the metastatic setting\n\nExclusion Criteria:\n\nStudy Group 1 and Study Group 2\n\n* Pregnancy or breastfeeding\n* Patients who at time of data collection for this study are participating in or have participated in an interventional study that remains blinded.\n\nNo other specific exclusion criteria are defined, as patients will be treated according to the proposed indication statements in the SmPC.",{"count":210,"type":19},2295,"Trastuzumab deruxtecan (T-DXd) as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.\n\nBased on the extended therapeutic indication of Trastuzumab deruxtecan (Enhertu®), a new patient population will be enrolled, comprising adult patients with unresectable or metastatic HR-positive, HER2-low, or HER2-(ultra)low breast cancer who have received at least one endocrine therapy in the metastatic setting and are not considered suitable for endocrine therapy as the next line of treatment.",[213,25,214,215],"Unresectable Breast Cancer","HER2-low Expressing Breast Cancer","HER2-(Ultra)Low Expressing Breast Cancer",[213,25,214,217,218,219],"Trastuzumab Deruxtecan","Enhertu®","HER2-(ultra)low Expressing Breast Cancer",{"date":146,"type":32},{"date":222,"type":32},"2023-10-24",{"date":224,"type":19},"2030-12-31",{"name":226,"class":128},"Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company",211,{"id":229,"slug":4,"hasResults":11,"nctId":230,"briefTitle":231,"officialTitle":232,"acronym":4,"eligibilityCriteria":233,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":234,"targetDuration":4,"studyType":20,"phases":236,"briefSummary":237,"conditions":238,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":195,"lastUpdatePostDateStruct":241,"startDateStruct":243,"completionDateStruct":245,"leadSponsor":247,"locationsCount":40},"100406500","NCT04573231","Evaluation of PSMA in HER2- AR+ Metastatic Breast Cancer","Evaluation of Prostate Specific Membrane Antigen (PSMA) in HER2-negative, Androgen Receptor (AR)-Positive Metastatic Breast Cancer With 18F-DCFPyL PSMA-based PET\u002FCT","Inclusion Criteria:\n\n* Patients diagnosed with metastatic HER2-negative breast cancer AR expression of ≥ 10%\n\nExclusion Criteria:\n\n* Other (non-breast) known active malignancy. Participants with previously treated cancers which are in remission or have no evidence of disease are eligible.\n* Unable to lie flat during or tolerate PET\u002FCT\n* Participants with any medical condition or other circumstances that, in the opinion of the investigator, compromise the safety or compliance of the subject to produce reliable data or completing the study\n* Women of childbearing potential must not be pregnant or breast feeding (pregnancy test negative within 7 days prior to PET\u002FCT",{"count":235,"type":19},13,[50],"The purpose of this research is to determine the expression of prostate specific membrane antigen (PSMA) in human epidermal growth factor receptor 2 (HER2)-negative, androgen receptor (AR)-positive metastatic breast cancer, and to determine its role in resistance to the anti-androgen, bicalutamide. The investigators hypothesize that PSMA expression will correlate with resistance to anti-androgen therapies, as has been documented in prostate cancer, and this can be used to select patients most likely to benefit from these therapies in future clinical trials. 15 people with HER2-negative, AR-positive metastatic breast cancer will be enrolled and be on study for about 3 days.",[239,240,25],"Breast Cancer","HER2-negative Breast Cancer",{"date":242,"type":32},"2026-06-25",{"date":244,"type":32},"2021-05-24",{"date":246,"type":19},"2026-07",{"name":248,"class":39},"University of Wisconsin, Madison",{"id":250,"slug":4,"hasResults":11,"nctId":251,"briefTitle":252,"officialTitle":253,"acronym":4,"eligibilityCriteria":254,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":255,"targetDuration":4,"studyType":20,"phases":257,"briefSummary":259,"conditions":260,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":265,"lastUpdatePostDateStruct":266,"startDateStruct":267,"completionDateStruct":269,"leadSponsor":271,"locationsCount":273},"100541015","NCT06324357","Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread","Beamion BCGC-1: A Phase Ib Dose Escalation and Phase II Dose Optimization, Randomized, Open-label, Multicenter Trial of Oral Zongertinib (BI 1810631) Alone or in Combination With Other Agents for the Treatment of Patients With Advanced HER2+ Metastatic Breast Cancer (mBC), Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (mGEAC), or Metastatic Colorectal Cancer (mCRC)","Inclusion criteria:\n\n* Patients ≥18 years of age or over the legal age of consent in countries where that is greater than 18 years at the time of signature of the informed consent form (ICF)\n* Cohorts A to K and Cohort O: Documented Human epidermal growth factor receptor 2 overexpressing and\u002For amplified (HER2+), metastatic breast cancer (mBC) or metastatic gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma (mGEAC).\n* Cohorts L (L-ext), M, and N (metastatic colorectal cancer (mCRC)): Documented Human epidermal growth factor receptor 2 (HER2) overexpression\u002Famplification according to American Society of Clinical Oncology\u002FCollege of American Pathologists (ASCO\u002FCAP) gastric cancer guidelines and according to the result of local testing.\n* For dose optimization and justification (Phase II): Patient must provide tumor tissue from locations not radiated prior to biopsy, if possible, collected through archival tissue\n* History of prior treatment lines in palliative setting:\n\n  * For cohorts A, B, C, D, E, F, G, H, I, I-ext, J, J-ext, K and O documented investigator assessed progression after HER2-directed treatment for unresectable locally advanced or metastatic disease (For Cohorts D, H, I (I-ext), J (J-ext) - patients must have been pretreated with trastuzumab deruxtecan (T-DXd) and have progressed or have been intolerant to previous T-DXd).\n  * For cohorts L, L-ext, M and N documented progression or recurrence of disease during or following their latest line of therapy. Patients must have had at least one prior line of therapy for locally advanced unresectable disease or metastatic disease (adjuvant and neoadjuvant therapy excluded) and documented disease progression or recurrence of disease during or following their latest line of therapy. In the opinion of the Investigator, patients must be unlikely to tolerate or derive clinically meaningful benefit from further standard of care therapy known to prolong survival.\n* Presence of at least one measurable lesion according to RECIST 1.1\n* Eastern Cooperative Oncology Group (ECOG) score of 0 or 1\n* Adequate organ function based on laboratory values Further inclusion criteria apply.\n\nExclusion criteria:\n\n* Previous treatment with:\n\n  * Any small molecule HER2 inhibitor in the palliative setting in Cohorts D, E, F, H, L, L-ext, M, and N. In Cohort D allowed in up to 15 patients in each dose level (DL).\n  * T-DXd in Cohorts E and F. In Cohort E allowed in up to 15 patients in each DL.\n  * trastuzumab emtansine (T-DM1) in the palliative setting in Cohort D and H. In Cohort H allowed in up to 15 patients in each DL.\n  * Capecitabine in Cohort D and H. In Cohort D allowed in up to 15 patients in each DL\n* Presence of uncontrolled and\u002For symptomatic brain metastases, or leptomeningeal disease\n* Mean resting corrected QT interval (QT interval corrected for heart rate by Fridericia´s formula (QTcF)) \\>470 msec.\n* Any factors that increase the risk of QT interval corrected for heart rate (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, personal or family history of long QT syndrome or unexplained sudden death under 40 years-of-age.\n* Ejection fraction \\\u003C50% or the lower limit of normal of the institutional standard within 28 days prior to randomization\n* History of (non-infectious) interstitial lung disease (ILD)\u002Fpneumonitis that required steroids, current ILD\u002Fpneumonitis, or where suspected ILD\u002Fpneumonitis cannot be ruled out by imaging at screening Further exclusion criteria apply.",{"count":256,"type":19},768,[258,50],"PHASE1","This study is open to adults aged 18 years and older with different types of HER2+ cancer that has spread and cannot be removed by surgery. People can take part in this study if their tumours show HER2 aberrations and previous treatment was not successful. The purpose of this study is to find a suitable dose of zongertinib that people with different types of HER2+ cancer that has spread can tolerate best when taken together with trastuzumab deruxtecan (T-DXd), with trastuzumab emtansine (T-DM1), with trastuzumab and capecitabine, with zanidatamab, or with mFOLFOX6 (with or without trastuzumab). Another purpose is to check whether zongertinib alone and in combination with other treatments can make tumours shrink. Zongertinib inhibits HER2. HER2 causes cancer cells to grow.\n\nIn this study, participants receive treatment in cycles. Study participants are treated with zongertinib alone or in combination with other treatments. This study has 2 parts. In Part 1, participants in different groups receive increasing doses of zongertinib. In Part 2, participants are put into different groups by chance. Each group receives a different dose of zongertinib. Every participant has an equal chance of being in each group.\n\nDuring the study, the participants visit the study site regularly. In this study, researchers want to find the highest dose of zongertinib that participants can tolerate when taken together with other treatments. To find this out, researchers look at certain severe health problems that a number of participants have. The doctors regularly check the size of the tumour with imaging methods (CT\u002FMRI) during the study. The doctors also regularly check participants' health and take note of any unwanted effects.",[25,261,262,263,264],"Metastatic Gastric Adenocarcinoma","Gastroesophageal Junction Adenocarcinoma","Esophageal Adenocarcinoma","Colorectal Cancer","2026-06-23",{"date":195,"type":32},{"date":268,"type":32},"2024-06-03",{"date":270,"type":19},"2029-01-08",{"name":272,"class":128},"Boehringer Ingelheim",108,{"id":275,"slug":4,"hasResults":11,"nctId":276,"briefTitle":277,"officialTitle":278,"acronym":4,"eligibilityCriteria":279,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":280,"targetDuration":4,"studyType":20,"phases":282,"briefSummary":283,"conditions":284,"keywords":287,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":296,"lastUpdatePostDateStruct":297,"startDateStruct":298,"completionDateStruct":300,"leadSponsor":302,"locationsCount":304},"100579664","NCT06827236","A Clinical Study to Find the Optimal Dose of an Investigational Treatment Called BNT323 When Used in Combination With Another Investigational Treatment, BNT327, and to Test if That Combination Treatment is Safe and Beneficial for Patients With Advanced Breast Cancer","A Phase I\u002FII, Multi-site, Open-label, Two-part Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of BNT323 in Combination With BNT327 in Participants With Advanced Breast Cancer","Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):\n\n* Have pathologically documented BC that:\n\n  * Is locally advanced, unresectable or metastatic.\n  * Has a confirmed HER2 status as determined by the local laboratory as standard of care testing prior to study screening (Part 1, Part 2 Cohorts 2 and 4) or the central laboratory (Part 2, Cohorts 1 and 3) from the most recently collected pre-randomization tumor sample.\n  * Has a documented history of HER2 expression consistent with the subgroup definitions (i.e., HER2-low, HER2-ultralow, HER2-null, HER2-positive, or TNBC) as per current American Society of Clinical Oncology\u002FCollege of American Pathologists guidelines.\n* Have measurable disease defined by RECIST v1.1.\n* Has left ventricular ejection fraction ≥55% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization\u002Fenrollment.\n\nKey Exclusion Criteria:\n\n* Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.\n* Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events.\n* Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization\u002Fenrollment.\n* Have a history of (non-infectious) interstitial lung disease (ILD)\u002Fpneumonitis that required steroids, have current ILD\u002Fpneumonitis, or where suspected ILD\u002Fpneumonitis cannot be ruled out by imaging at screening.\n* Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugates with topoisomerase I inhibitor payloads such as trastuzumab deruxtecan.\n* Have received any of the following therapies or drugs prior to the initiation of the study:\n\n  * Participants who have received prior treatment with BNT323.\n  * Participants who received prior treatment with a programmed death-ligand 1 (PD-L1) \u002F vascular endothelial growth factor (VEGF) bispecific antibody. Note: Prior treatment with programmed death 1 (PD-1)\u002FVEGF bispecific antibodies, PD-1\u002FPD-L1 inhibitors or anti-VEGF therapies are permitted.\n  * Have received other systemic immunostimulatory agents or immunosuppressive therapies (such as interferon-α, interleukin-2, or methotrexate) within 4 weeks prior to the initiation of study treatment or are within five half-lives of the treatment drug (whichever is longer). Exception: excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).\n  * Have received systemic corticosteroids (at a dosage greater than 10 mg\u002Fday of prednisone or an equivalent dose of other corticosteroids) within 3 weeks prior to the initiation of study treatment.\n\nNOTE: Other protocol defined Inclusion\u002FExclusion criteria apply.",{"count":281,"type":19},380,[258,50],"This is a Phase I\u002FII, multi-site, open-label, two-part study designed to evaluate the efficacy, safety, optimized dose and contribution of components of BNT323 (also known as trastuzumab pamirtecan and DB-1303) in combination with BNT327 (also known as pumitamig and PM8002) in participants with hormone receptor-positive (HR+) or hormone receptor-negative (HR-), Human epidermal growth factor receptor (HER)2-positive, HER2-low (immunohistochemistry \\[IHC\\] 1+ or IHC 2+\u002Fin situ hybridization -), HER2-ultralow (IHC 0, with membrane staining) or HER2-null breast cancer (BC), or triple-negative breast cancer (TNBC).",[285,286,25],"Locally Advanced Breast Cancer","Unresectable Breast Carcinoma",[288,289,290,291,292,293,294,295],"Breast Cancer (BC)","Human epidermal growth factor receptor 2 (HER2)","IHC scores 0, 1+, 2+, and 3+","Antibody drug conjugate (ADC)","Programmed Death-1 (PD-1)","Programmed Death Ligand-1 (PD-L1)","Programmed Death-1 monoclonal antibodies","Anti vascular endothelial growth factor-A (anti-VEGF-A)","2026-06-22",{"date":265,"type":32},{"date":299,"type":32},"2025-04-23",{"date":301,"type":19},"2029-08",{"name":303,"class":128},"BioNTech SE",56,{"id":306,"slug":4,"hasResults":11,"nctId":307,"briefTitle":308,"officialTitle":309,"acronym":4,"eligibilityCriteria":310,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":311,"targetDuration":4,"studyType":20,"phases":313,"briefSummary":314,"conditions":315,"keywords":326,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":344,"lastUpdatePostDateStruct":345,"startDateStruct":346,"completionDateStruct":347,"leadSponsor":349,"locationsCount":351},"100564176","NCT06625775","Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors","A Phase 1a\u002F1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-10203 in Subjects With Advanced Solid Tumors (The BREAKER-101 Study)","Inclusion Criteria:\n\n* Locally advanced and unresectable or metastatic HER2-positive advanced breast cancer (aBC), HR-positive\u002FHER2-negative advanced breast cancer, KRAS mutant advanced colorectal cancer (aCRC), or KRAS mutant advanced non-small cell lung cancer (aNSCLC)\n* Measurable disease by RECIST v1.1 (except for HR-positive HER2-negative aBC where evaluable bone-only disease is permitted)\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1\n* Adequate LVEF assessed by ECHO or MUGA (BBO-10203 + Trastuzumab cohorts only)\n* Stable brain metastases\n* Patients with HER2-positive aBC: Must have had at least 2 prior lines of anti-HER2-directed therapy. Only 1 prior line is acceptable where there is no other regionally available standard of care (SoC)\n* Monotherapy Cohort patients with HR-positive, HER2-negative aBC, KRAS mutant aCRC or aNSCLC: Must have progression on, or disease recurrence after at least one line of SOC treatment or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from SoC therapy\n* BBO-10203 + Fulvestrant combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, must have been treated with a CDK4\u002F6i\n* BBO-10203 + Fulvestrant + ribociclib combination cohort patients with HR-positive, HER2-negative aBC: confirmed PIK3CA mutation, no prior systemic therapy in the aBC setting permitted\n* BBO-10203 + FOLFOX + Bevacizumab combination cohort patients with KRAS mutant aCRC: One prior line of irinotecan-containing therapy for locally advanced or metastatic CRC is allowed but not required\n\nExclusion Criteria:\n\n* Patients with KRAS mutant aCRC who have KRAS G12R mutation, BRAFV600E mutation, HER2amp, or dMMR\u002FMSI-H tumors\n* Patients with KRAS mutant aNSCLC who have KRAS G12R mutation, or tumors with other targetable driver mutations (eg, EGFR, anaplastic lymphoma kinase, ROS1\u002FBRAF\u002FRET\u002FMET\u002FEGFR exon20 insertion\u002FNTRK\u002FHER2)\n* Patients with untreated and\u002For non-stable brain metastases\n\nOther inclusion\u002Fexclusion criteria are specified in the protocol",{"count":312,"type":19},392,[258],"First in human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of BBO-10203, a PI3Kα:RAS breaker, alone and in combination with other anti-cancer agents in patients with advanced solid tumors.",[316,25,317,318,319,320,321,322,323,324,325],"Solid Tumor, Adult","Advanced Breast Cancer","HER2 Mutation-Related Tumors","HER2-positive Metastatic Breast Cancer","KRAS Mutant Metastatic Colorectal Cancer","Metastatic Lung Cancer","Metastatic Colorectal Cancer","Advanced Lung Cancer","HR-positive, HER2-negative Advanced Breast Cancer","HER2-positive Advanced Breast Cancer",[327,328,329,330,331,332,333,334,335,336,337,338,339,340,341,342,343],"BREAKER-101","BridgeBio Oncology Therapeutics","BBOT","Phase1","Phase 1a\u002F1b","Trastuzumab","Breast","Colorectal","Non-Small Cell Lung Cancer","CRC","NSCLC","Metastatic Cancer","Advanced Cancer","HER2-positive","HR-positive","HR-positive, HER2-negative","HER2-negative","2026-06-18",{"date":265,"type":32},{"date":148,"type":32},{"date":348,"type":19},"2028-11",{"name":350,"class":128},"TheRas, Inc., d\u002Fb\u002Fa BBOT (BridgeBio Oncology Therapeutics)",40,{"id":353,"slug":4,"hasResults":11,"nctId":354,"briefTitle":355,"officialTitle":356,"acronym":4,"eligibilityCriteria":357,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":358,"targetDuration":4,"studyType":20,"phases":360,"briefSummary":361,"conditions":362,"keywords":364,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":370,"lastUpdatePostDateStruct":371,"startDateStruct":372,"completionDateStruct":374,"leadSponsor":376,"locationsCount":378},"100574257","NCT06756932","BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)\u002FHuman Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer","A Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-21447 (a Bcl-2 Inhibitor) Combinations for Patients With HR+\u002FHER2- Metastatic Breast Cancer","Inclusion Criteria:\n\n* Histologically or cytologically confirmed HR+\u002FHER2- metastatic breast cancer. Part 1A and 1B: Participants must have received ≥ 1 prior line(s) of treatment for advanced\u002Fmetastatic disease, including prior endocrine therapy and CDK4\u002F6 inhibitor in either the adjuvant or advanced\u002Fmetastatic setting. Part 2: Participants must have received 1-3 prior line(s) of treatment for advanced\u002Fmetastatic disease, including prior endocrine therapy and CDK4\u002F6 inhibitor in either the adjuvant or advanced\u002Fmetastatic setting.\n* Female participants will be required (either continue ongoing or initiate as soon as feasible) to have ovarian function suppression using gonadotropin-releasing hormone (GnRH) agonists (such as goserelin) or be postmenopausal.\n* Male participants may be required to use GnRH agonists when being treated with fulvestrant at the discretion of the investigator.\n* Participants must have a stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1.\n* Adequate organ function.\n* Female participants of childbearing potential and nonsterile male participants with female partners of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study and for 7 days after the last dose of BGB-21447, 6 months after the last dose of BGB-43395, and 2 years after the last dose of fulvestrant.\n* Food effect substudy only: Participants who are able and willing to fast overnight (≥ 10 hours) and consume a high-fat meal.\n\nExclusion Criteria:\n\n* Prior Bcl-2 inhibitor exposure. For triplet combination cohorts only: Prior therapy selectively targeting CDK4.\n* Known leptomeningeal disease or uncontrolled, untreated brain metastases.\n* Any malignancy ≤ 3 years before the first dose of study treatment(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, treated papillary thyroid carcinoma, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).\n* For Part 1B: Uncontrolled diabetes.\n* History of hepatitis B or active Hepatitis C infection\n* China Only: Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA \\> 500 IU\u002Fml (or \\> 2500 copies\u002Fml) at screening.\n\nNote: Other protocol defined Inclusion\u002FExclusion criteria may apply.",{"count":359,"type":19},120,[258],"This is a dose escalation and dose expansion study to assess the safety and tolerability of BGB-21447 (a B-cell leukemia\u002Flymphoma 2 inhibitor, Bcl-2i) in combination with fulvestrant, with or without BGB-43395 (cyclin-dependent kinase 4 inhibitor, CDK4i), in adults with HR+\u002FHER2- metastatic breast cancer.",[363,240,25],"Hormone-receptor-positive Breast Cancer",[365,366,367,368,369],"BGB-21447","BGB-43395","metastatic breast cancer","Bcl-2i","CDK4i","2026-06-17",{"date":296,"type":32},{"date":373,"type":32},"2025-02-04",{"date":375,"type":19},"2027-07-30",{"name":377,"class":128},"BeOne Medicines",14,{"id":380,"slug":4,"hasResults":11,"nctId":381,"briefTitle":382,"officialTitle":383,"acronym":384,"eligibilityCriteria":385,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":386,"targetDuration":4,"studyType":20,"phases":388,"briefSummary":389,"conditions":390,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":370,"lastUpdatePostDateStruct":391,"startDateStruct":392,"completionDateStruct":394,"leadSponsor":396,"locationsCount":398},"100492782","NCT05696626","Evaluation of Lasofoxifene Combined With Abemaciclib Compared With Fulvestrant Combined With Abemaciclib in Locally Advanced or Metastatic ER+\u002FHER2- Breast Cancer With an ESR1 Mutation","An Open Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of the Combination of Lasofoxifene and Abemaciclib to the Combination of Fulvestrant and Abemaciclib for the Treatment of Pre- and Postmenopausal Women and Men With Locally Advanced or Metastatic ER+\u002FHER2- Breast Cancer With an ESR1 Mutation","ELAINEIII","Inclusion Criteria:\n\n1. Pre- or postmenopausal women or men.\n2. Locally advanced and\u002For metastatic ER+ breast cancer with radiological or clinical evidence of progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease.\n3. Histological or cytological confirmation of ER+\u002FHER2 - disease\n4. No evidence of progression for at least 6 months on an AI\u002FCDKi combination for advanced breast cancer.\n5. At least 1 or more ESR1 point mutations in the ESR1 ligand binding domain as assessed in cell- free ctDNA obtained from a blood or breast cancer tissue.\n6. Locally advanced or metastatic breast cancer with at least 1 measurable (according to RECIST 1.1) lesion with or without non-measurable lesions.\n7. Subjects may have received 1 cytotoxic chemotherapy regimen in the metastatic disease setting prior to study entry, but must have recovered from chemotherapy acute toxicity excluding alopecia and Grade 2 peripheral neuropathy.\n8. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1\n9. Adequate organ function\n10. Able to swallow tablets\n11. Brain metastases are allowed only if the following 4 parameters hold:\n\n    1. Asymptomatic,\n    2. Definitively treated (e.g., radiotherapy, surgery),\n    3. Not requiring steroids up to 4 weeks before study treatment initiation, AND\n    4. Central nervous system disease stable for \\>3 months prior to registration as documented by magnetic resonance imagining (MRI).\n12. Able to understand and voluntarily sign a written informed consent before any screening procedures.\n13. Every attempt should be made to obtain a biopsy of metastatic breast cancer tissue, when safe and feasible, to provide histological or cytological confirmation of ER+\u002FHER2- disease as assessed by a local laboratory, according to American Society of Clinical Oncology\u002FCollege of American Pathologists guidelines, using slides, paraffin blocks, or paraffin samples. If a biopsy is done, it may undergo genomic testing at some point to assess for ESR1 mutations and correlation with ctDNA results. If a biopsy is not possible or inappropriate from a clinical standpoint, the ER and HER2 status from the subject's most recent biopsy must confirm that the subject is ER+ and HER2\n\nExclusion Criteria:\n\n1. Lymphangitic carcinomatosis involving the lung.\n2. History of Grade 3 or Grade 4 interstitial lung disease (ILD) on previous therapy.\n3. Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.\n4. Prior progression of disease on abemaciclib, fulvestrant, or other selective estrogen receptor degrader (SERD) therapy.\n5. Subjects with a known hypersensitivity to fulvestrant or to any of the excipients\n6. Radiotherapy within 30 days prior to Visit 0 (Day 1) except in case of localized radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to Visit 0 (Day 1). Subjects must have recovered from radiotherapy toxicities prior to Visit 0 (Day 1).\n7. Known RB1 mutations or deletions that in the opinion of the investigator confer resistance to CDK4\u002F6i. (Screening for RB1 mutation is not required for entry.)\n8. History of long QTc (Q-T interval corrected for heart rate) syndrome or a QTc of \\>480 msec.\n9. History of a pulmonary embolus (PE), deep vein thrombosis (DVT), or any known thrombophilia, unless the event occurred greater than 6 months prior to screening and the subject is treated with chronic anticoagulant therapy such as apixaban (Eliquis) or rivaroxaban (Xarelto).\n10. Lasofoxifene is not recommended for use in subjects with conditions that place them at increased risk for VTEs (such as severe congestive heart failure \\[CHF\\] or prolonged immobilization).\n11. On concomitant strong CYP3A4 inhibitors.\n12. On strong and moderate CYP3A4 inducers.\n13. Any significant co-morbidity that would impact the study or the subject's safety, including subjects with significant malabsorption.\n14. Active systemic bacterial or fungal infection (requiring intravenous \\[IV\\] antibiotics or antifungals at the time of initiating study treatment).\n15. Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).\n16. History of malignancy within the past 5 years (excluding breast cancer), except basal cell or squamous cell carcinoma of the skin curatively treated by surgery.\n17. Positive serum pregnancy test (only if premenopausal).\n18. Sexually active premenopausal women and men unwilling to use double-barrier contraception.\n19. Women who are breast feeding\n20. History of non-compliance to medical regimens.\n21. Unwilling or unable to comply with the protocol.\n22. Current participation in any clinical research trial involving an investigational drug or device within the last 30 days.\n23. Subjects with a history of familial hypertriglyceridemia or fasting triglyceride levels \\>880 mg\u002FdL at screening.\n24. Fasting triglyceride level \\>300 mg\u002FdL and ≤880 mg\u002FdL at screening. Subjects may be retested and enrolled if they have a repeat fasting triglyceride level less than or equal to 300 mg\u002FdL prior to enrollment (e.g., after adjustment with diet and\u002For treatment).\n25. Fasting cholesterol level \\>400 mg\u002FdL at screening. Subjects may be retested and enrolled if they have a repeat fasting cholesterol level less than or equal to 400 mg\u002FdL prior to enrollment (e.g., after adjustment with diet and\u002For treatment).",{"count":387,"type":19},600,[140],"The goal of this clinical trial is to assess the efficacy, safety and tolerability of the combination of lasofoxifene and abemaciclib compared to fulvestrant and abemaciclib for the treatment of pre- and postmenopausal women and men who have previously received ribociclib or palbociclib-based treatment and have locally advanced or metastatic estrogen receptor positive (ER+)\u002Fhuman epidermal growth factor 2 negative (HER2-) breast cancer with an estrogen receptor 1 (ESR1) mutation.\n\nThe main question the study aims to answer is:\n\n• To compare the efficacy of the combination of lasofoxifene and abemaciclib with that of fulvestrant and abemaciclib Participants will receive either receive 5 mg\u002Fd of oral lasofoxifene plus oral abemaciclib 150 mg twice a day or the combination of fulvestrant 500 mg intramuscular (IM) on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day.",[25],{"date":296,"type":32},{"date":393,"type":32},"2023-10-31",{"date":395,"type":19},"2028-04",{"name":397,"class":128},"LeonaBio",224,{"id":400,"slug":4,"hasResults":11,"nctId":401,"briefTitle":402,"officialTitle":403,"acronym":4,"eligibilityCriteria":404,"healthyVolunteers":11,"sex":180,"minAge":16,"maxAge":4,"enrollmentInfo":405,"targetDuration":4,"studyType":20,"phases":407,"briefSummary":408,"conditions":409,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":370,"lastUpdatePostDateStruct":412,"startDateStruct":413,"completionDateStruct":415,"leadSponsor":417,"locationsCount":378},"100483291","NCT05573126","Phase 1\u002F2 Study to Evaluate EP0062 as Monotherapy and in Combination in Patients With Advanced or Metastatic AR+\u002FHER-2-\u002FER+ Breast Cancer","A Modular, Open-Label, Multi-Centre Phase 1\u002F2 Dose-Finding, Optimisation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of EP0062 as Monotherapy and in Combination in Patients With Relapsed Locally Advanced or Metastatic AR+\u002FHER-2-\u002FER+ Breast Cancer","Inclusion Criteria:\n\n1. Women 18 years or older at the time of informed consent\n2. Histologically proven diagnosis of breast cancer with evidence of metastatic or locally advanced breast adenocarcinoma as defined by the American Joint Committee on Cancer\u002FUnion for International Cancer Control\u002FTumour Node Metastases (AJCC\u002FUICC TNM) staging classification (8th Ed, 2017) and where no conventional therapy is available or considered appropriate by the Investigator or is declined by the patient\n3. Availability of archival tumour sample (formalin-fixed, paraffin-embedded block(s) or slides from a primary tumour or biopsy of a metastatic tumour lesion or lesions); in the absence of an archival tumour sample, or if only archival bone tissue is available, a fresh biopsy will need to be collected\n4. Biopsy-proven AR+ and ER+ breast cancer\n\n   * For Module A, AR+ breast cancer is defined as ≥ 10% AR nuclei staining by central immunohistochemistry (IHC) using the Ventana assay\n   * For Modules B and C, AR+ breast cancer is defined as ≥ 30% AR nuclei staining by central IHC using the Ventana assay\n5. HER2-negative breast cancer, defined as negative by fluorescence in situ hybridisation (FISH) or IHC score of 0 or 1+. If IHC is equivocal at 2+, a negative FISH test (HER2\u002FAmplification of the centromeric region of chromosome 17)CEP17 ratio of \\\u003C2.0) is required\n6. Postmenopausal, as defined by at least one of the following:\n\n   1. Age over 60 years\n   2. Amenorrhea \\> 12 months at the time of informed consent and an intact uterus, with follicle-stimulating hormone (FSH) and oestradiol in the postmenopausal ranges (as per local practice)\n   3. FSH and oestradiol in the postmenopausal ranges (as per local practice) in women aged \\\u003C55 years who have undergone hysterectomy\n   4. Prior bilateral oophorectomy\n7. Module B arm 1: patients who have progressed on ≤ 2 prior lines of endocrine therapy, including a prior CDK4\u002F6 inhibitor.\n8. Module B arm 2: patients who have progressed on ≤ 2 prior lines of endocrine therapy in advanced\u002Fmetastatic setting, including prior CDK4\u002F6 inhibitor\n9. Module B arm 3: patients who have progressed on treatment with a prior CDK4\u002F6 inhibitor plus an aromatase inhibitor as initial therapy or recurrence on\u002Fafter treatment with a CDK4\u002F6 inhibitor plus endocrine therapy in the adjuvant setting.\n\nExclusion Criteria:\n\nPatients with any of the following will not be included in the study:\n\n1. Prior anti-cancer or investigational drug treatment within the following time windows:\n\n   * Any chemotherapy within 21 days prior to the first dose of study drug\n   * Any non-chemotherapy investigational anti-cancer drug \\\u003C 5 half-lives (28 days for biologics) or \\\u003C 14 days for small-molecule therapeutics or if half-life is not known\n   * Tamoxifen and aromatase inhibitors within 14 days prior to the first dose of study drug\n   * Fulvestrant or other investigational Selective Estrogen Receptor Degraders (SERDs) within 21 days prior to first dose of study drug\n2. Currently taking testosterone, methyltestosterone, oxandrolone, oxymetholone, danazol, fluoxymesterone, testosterone-like agents (e.g., dehydroepiandrosterone, androstenedione, and other androgenic compounds, including herbals), or antiandrogens\n3. Radiation therapy within 14 days prior to the first dose of study drug and scheduled to have radiation therapy during participation in this study. Short courses of palliative radiation therapy during the study might be allowed following discussion with and approval by the Medical Monitor. Palliative radiotherapy within 6 weeks prior to first dose of study drug is permitted\n4. Unresolved or unstable serious toxic side effects of prior chemotherapy or radiotherapy, i.e., ≥ Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except fatigue, alopecia, and Grade 2 chemotherapy-induced neuropathy\n5. Confirmed Corrected QT Interval by Fridericia (QTcF) \\> 470 ms on screening ECG, or history of torsades de pointes (TdP), or history of congenital long QT syndrome, or immediate family history of long QT syndrome, unexplained sudden death at a young age, or sudden cardiac death\n6. Any other clinically important abnormalities in rhythm, conduction, or morphology on resting ECG (e.g., complete left bundle branch block, third-degree heart block); rate-controlled atrial fibrillation is permitted\n7. Concomitant medications that prolong the corrected QT interval and\u002For increase the risk for TdP that cannot be discontinued or substituted with another drug within 5 half-lives or 14 days before the first dose of study drug, whichever is longer\n8. Congestive heart failure Grades II-IV according to the New York Heart Association at the time of screening\n9. Myocardial infarction or unstable angina within the previous 6 months\n10. Patients receiving medications that are known to be strong inhibitors or inducers of CYP3A4 within 5 half-lives or 14 days, whichever is longer, before the first dose of study drug\n11. Prior treatment with selected combination agent",{"count":406,"type":19},95,[258,50],"The aim of this study is to identify the optimal dose for EP0062 as monotherapy and in combination with standard-of-care therapies to assess its Safety, Tolerability, Pharmacokinetics, and Efficacy in Patients with Relapsed Locally Advanced or Metastatic AR+\u002FHER-2-\u002FER+ Breast Cancer",[410,411,25],"Hormone Receptor-positive Breast Cancer","Hormone Receptor Positive HER-2 Negative Breast Cancer",{"date":296,"type":32},{"date":414,"type":32},"2023-01-11",{"date":416,"type":19},"2028-02",{"name":418,"class":128},"Ellipses Pharma",{"id":420,"slug":4,"hasResults":11,"nctId":421,"briefTitle":422,"officialTitle":423,"acronym":4,"eligibilityCriteria":424,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":425,"targetDuration":4,"studyType":20,"phases":426,"briefSummary":427,"conditions":428,"keywords":430,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":431,"lastUpdatePostDateStruct":432,"startDateStruct":433,"completionDateStruct":435,"leadSponsor":437,"locationsCount":439},"100438230","NCT04986579","Scalp Cooling in MBC","Assessing the Impact of Scalp Cooling in With Metastatic Breast Cancer","Inclusion Criteria:\n\n* Men and women with a diagnosis of metastatic invasive breast cancer with a ECOG PS≤2\n* Participant is ≥ 18 years old.\n* Hair present at baseline.\n* One of the following full dose chemotherapy regimens must be planned for at least 4 cycles:\n\n  * Sacituzumab govitecan (IMMU-132) 10 mg\u002Fkg administered intravenously on days 1 and 8 of each 21-day cycle\n  * Trastuzumab deruxtecan 5.4 mg\u002Fkg administered intravenously once every 3 weeks\n  * Eribulin 1.4 mg\u002Fm2 administered intravenously on days 1 and 8 of each 21-day cycle\n* The Paxman Scalp Cooling System must be initiated with the first dose of therapy in participants that elect to participate in the scalp cooling group.\n\nExclusion Criteria:\n\n* Known hematological malignancies (i.e. leukemia or lymphoma)\n* Known scalp metastases.\n* Baseline alopecia (defined CTCAE 5.0 grade \\> 0, see Appendix B)\n* Subjects with cold agglutinin disease or cold urticaria.\n* Subjects who are scheduled for bone marrow ablation chemotherapy.\n* Personal history of migraines, cluster or tension headaches as defined as actual medical diagnosis by a physician and\u002F or prescribed medications. If personal history of migraines was related to a past medical problem that is now resolved, the subject may go on study at the discretion of the Principal Investigator.\n* Subjects who have lichen planus or lupus.\n* Participants who are receiving any additional anti-cancer agents",{"count":359,"type":19},[50],"This research is being done to compare rates of hair loss of people with metastatic breast who use scalp cooling versus those who do not use scalp cooling after receiving standard of care treatment with either sacituzumab govitecan, trastuzumab deruxtecan, or eribulin.\n\nThe name of the study intervention involved in this study is:\n\n* Paxman Scalp Cooling System",[25,429],"Chemotherapy-induced Alopecia",[25,429],"2026-06-16",{"date":344,"type":32},{"date":434,"type":32},"2021-10-07",{"date":436,"type":19},"2030-06-01",{"name":438,"class":39},"Dana-Farber Cancer Institute",2,{"id":441,"slug":4,"hasResults":11,"nctId":442,"briefTitle":443,"officialTitle":444,"acronym":445,"eligibilityCriteria":446,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":447,"targetDuration":4,"studyType":75,"phases":4,"briefSummary":449,"conditions":450,"keywords":451,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":454,"lastUpdatePostDateStruct":455,"startDateStruct":456,"completionDateStruct":458,"leadSponsor":460,"locationsCount":462},"100592511","NCT06994377","Emotional Distress in Patients With Metastatic Breast Cancer in First Line of Therapy","The Impact of Emotional Distress on First Line Therapy in Patients With Metastatic Breast Cancer (EIRENE): a Prospective Observational Study","EIRENE","Inclusion Criteria:\n\n* Age over 18 years\n* Confirmed histological diagnosis of breast cancer\n* No prior treatment for advanced\u002Fmetastatic cancer\n* Indication to receive first-line therapy as per standard clinical practice based on the disease subtype:\n\n  1. cohort A (HR-\u002FHER2-, PD-L1+): pembrolizumab or atezolizumab + chemotherapy\n  2. cohort B (HR-\u002FHER2-, PD-L1-): chemotherapy\n  3. cohort C (HR+\u002FHER2-): CDK4\u002F6 inhibitor + endocrine therapy\n  4. cohort D (HER2+): chemotherapy + trastuzumab and pertuzumab\n* Presence of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 and\u002For Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) criteria\n* Able to provide full informed consent for the study\n\nExclusion Criteria:\n\n* Pre-existing severe psychiatric disorders or other conditions that could impair the ability to provide informed consent\n* Inability to complete questionnaires\n* Presence of another malignancy in the previous 3 years\n* Symptomatic brain metastases\n* Ongoing treatment with antidepressant and\u002For anxiolytic drugs",{"count":448,"type":19},1000,"Few data about the impact of emotional distress (ED) on treatment efficacy in patients with metastatic breast cancer (mBC) are available.\n\nAim of this study is to assess the outcomes of patients with mBC receiving first-line treatment according to the presence of baseline ED.",[25],[25,452,453],"Emotional Distress","First Line Therapy","2026-06-15",{"date":370,"type":32},{"date":457,"type":32},"2025-06-25",{"date":459,"type":19},"2029-06",{"name":461,"class":39},"European Institute of Oncology",37,{"id":464,"slug":4,"hasResults":11,"nctId":465,"briefTitle":466,"officialTitle":467,"acronym":4,"eligibilityCriteria":468,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":469,"enrollmentInfo":470,"targetDuration":4,"studyType":20,"phases":472,"briefSummary":473,"conditions":474,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":454,"lastUpdatePostDateStruct":475,"startDateStruct":476,"completionDateStruct":478,"leadSponsor":480,"locationsCount":482},"100441563","NCT05029999","CD40 Agonist, Flt3 Ligand, and Chemotherapy in HER2 Negative Breast Cancer","Phase 1 Pilot Study With Dose Expansion of Chemotherapy in Combination With CD40 Agonist and Flt3 Ligand in Metastatic HER2 Negative Breast Cancer","Inclusion Criteria:\n\n* Unresectable Stage III or Stage IV HER2 negative breast cancer (either triple negative or hormone receptor positive)\n\n  * Triple negative breast cancer for this study is defined as estrogen receptor \\\u003C10%, progesterone receptor \\\u003C10% by immunohistochemistry, and HER2- negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per routine clinical testing.\n  * Hormone receptor positive breast cancer for this study is defined as either estrogen receptor ≥10% or progesterone receptor ≥10% by immunohistochemistry, and HER2- negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per routine clinical testing.\n* Age 18 years or older\n* Performance status ECOG 0-2\n* Life expectancy ≥ 12 weeks\n* Documented progressive disease, based on radiographic, clinical or pathologic assessment, during or subsequent to last anticancer therapy. Patients who need to change systemic therapy for other indications such as toxicity that are otherwise eligible for this study may enroll with approval of the lead principal investigator.\n* For triple negative breast cancer patients, subject is in first to fourth line setting of treatment for metastatic or unresectable disease, and have received 0 to 3 prior regimens for metastatic or unresectable disease.\n* For hormone receptor positive breast cancer patients, subjects must have received prior cyclin dependent kinase inhibitor in the metastatic setting. They may have received up to 3 prior lines of chemotherapy and\u002For antibody drug conjugates for metastatic or unresectable disease.\n* Among triple negative breast cancer patients enrolled in the first line treatment setting, subjects must be PD-L1 negative by 22C3 assay and not be eligible for FDA approved standard of care chemotherapy and anti-PD-1\u002FPD-L1 combination therapy as alternative to this clinical trial. This does not apply if patients have previously received PD-1 or PD-L1 blockade as part of neoadjuvant or adjuvant therapy regimen.\n* Screening laboratory values must meet the following criteria:\n\n  * Neutrophils ≥ 1500\u002FuL\n  * Platelets ≥ 100 x10(9)\u002FL\n  * Hemoglobin ≥ 8 g\u002FdL Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.\n  * Creatinine ≤ 2 mg\u002FdL\n  * Creatinine clearance \\>30 mL\u002Fminute\n  * AST ≤ 2.5 X ULN without, and ≤ 5 x ULN with hepatic metastasis\n  * ALT ≤ 2.5 X ULN without, and ≤ 5 x ULN with hepatic metastasis\n  * Total Bilirubin ≤ 1.5 X ULN (except patients with Gilbert's syndrome or liver involvement, who must have a total bilirubin ≤ 2 X ULN)\n  * Alkaline phosphatase ≤ 2.5 X ULN without, and ≤ 5 x ULN with hepatic metastasis\n* All men as well as women of child bearing potential enrolled in this trial must agree to use effective contraception during the course of the trial and for at least 6 months after discontinuing study treatment. Patients and\u002For partners who are surgically sterile or postmenopausal are exempt from this requirement.\n\n  * 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: ( 1) has not undergone a hysterectomy or bilateral oophorectomy OR (2) 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* Provision of consent for pre-treatment and on-treatment biopsies. Biopsy sites must be soft tissue tumor lesions or accessible visceral diseases that can be biopsied with acceptable clinical risk (as judged by the investigator); are large enough to allow for the collection of tumor tissue for proposed correlative studies (e.g., anticipated goal of 6-8 cores preferred when feasible using a ≥ 18 gauge needle with an expected core sample length of 5 mm); and have not been irradiated prior to entry. This does not include bone lesions. This may exclude many lung lesions and small lesions.\n* Measurable disease allowing for serial assessment of at least one target lesion(s) by RECIST 1.1 criteria \\[100\\]. Target lesions selected for tumor measurements should be those where additional (e.g., palliative) treatments are not indicated or anticipated.\n* All residual toxicity related to prior anticancer therapies (excluding alopecia, grade 2 fatigue, vitiligo, endocrinopathies on stable replacement therapy, grade 2 neuropathy from taxanes or platinum and grade 2 hearing loss from platinum) must resolve to grade 1 severity or less (or returned to baseline) prior to receipt of study treatment.\n* Read, understood, and provided written informed consent, and if applicable, Health Insurance Portability and Accountability Act (HIPAA) authorization, after the nature of the study has been fully explained, and must be willing to comply with all study requirements and procedures.\n\nExclusion Criteria:\n\n* Among any patients enrolled in the first line treatment setting, tumors should not be PD-L1+ by 22C3 assays or eligible for FDA approved standard of care chemotherapy and anti-PD-1\u002FPD-L1 combination therapy as alternative to this clinical trial. This does not apply if patients have previously received PD-1 or PD-L1 blockade as part of neoadjuvant or adjuvant therapy regimen.\n* History of severe hypersensitivity reactions to mAbs.\n* Prior treatment with any anti-CD40 antibody or rhuFlt3L product.\n* Treatment with anthracycline in the metastatic setting.\n* Prior progression while on anthracycline based therapy or within 6 months of completing neoadjuvant or adjuvant anthracycline.\n* Prior history of acute myeloid leukemia (AML), or tumor with known Flt3 mutation\u002Famplification\n* Receipt of any antibody targeting T cell check point or co-stimulation pathways within 4 weeks, use of any other monoclonal based therapies within 4 weeks, and all other immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks prior to the planned start of study treatment.\n* Prior T-cell or other cell-based therapies within 12 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)\n* Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks, or radiopharmaceuticals (strontium, samarium) within 8 weeks prior to the first dose of study treatment.\n* Chemotherapy or antibody drug conjugate within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment.\n* Any kinase inhibitors within 2 weeks prior to the first dose of study treatment.\n* Major surgery within 4 weeks prior to the first dose of study treatment. Surgery requiring local\u002Fepidural anesthesia must be completed at least 72 hours before study drug administration and patients should be recovered.\n* Use of other investigational drugs within 4 weeks or 5 half-lives (whichever is longer) prior to study treatment administration.\n* Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment. Topical, inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if the patient is on a stable dose. Non-absorbed intraarticular corticosteroid and replacement steroids (≤ 10 mg\u002Fday prednisone or equivalent) will be permitted.\n* Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years.\n* Active, untreated central nervous system metastases.\n* Patients with known treated brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study enrollment. Continued use of steroids and\u002For anticonvulsants (in the absence of any suspicion of progressive brain metastases) is acceptable if ≤ equivalent of prednisone 10 mg daily. Brain MRI required on screening to document lack of progression.\n* Women who are pregnant or nursing. All female patients with reproductive potential must have a negative pregnancy test prior to starting treatment.\n* Active autoimmune disease or history of autoimmune disease or syndrome that required systemic steroids or immunosuppressive medications within the preceding 6 months, except for patients with vitiligo, endocrinopathies, or type 1 diabetes, Patients with mild asthma who require intermittent use of bronchodilators (such as albuterol) who have not been hospitalized for asthma in the preceding 6 months will not be excluded from this study.\n* Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, congestive heart failure (New York Heart Association Class III or IV or EF\\\u003C50%) related to primary cardiac disease, uncontrolled ischemic or severe valvular heart disease or any of the following within 6 months prior to the first dose of study treatment: myocardial infarction, severe\u002Funstable angina, coronary artery bypass graft, congestive heart failure, cerebrovascular accident, transient ischemic attack.\n* For patients with triple negative breast cancer- prior anthracycline therapy with a cumulative doxorubicin-equivalent dose greater than 240 mg\u002Fm2. 240 mg\u002Fm2 anthracycline is equivalent to 4 doses of anthracycline-based chemotherapy in the localized setting (generally 60 mg\u002Fm2 per dose). Notes from physicians demonstrating 4 prior cycles\u002Fdoses of anthracycline or if less than 60 mg\u002Fm2 specifying as such to estimate the total anthracycline dose is sufficient. Exact calculation based on mg received originally is not required.\n* For patients with hormone receptor positive breast cancer who have received a prior anthracycline therapy with a cumulative doxorubicin-equivalent dose exceeding 240 mg\u002Fm2 (as was part of standard-of-care regimens in the past), a cardiology evaluation is recommended to minimize potential risks of heart damage.\n* Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to the following: measles, mumps, rubella, varicella\u002Fzoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. The COVID-19 vaccines available in the United States are not live vaccines and are allowed if the final vaccine dose (of a regimen that requires more than 1 dose) is received at least 1 week prior to study enrollment.\n* History of (non-infectious) pneumonitis or has current pneumonitis. This includes asymptomatic infiltrates on screening chest CT scan that are felt by the investigator to potentially be an inflammatory process (i.e. grade 1 pneumonitis).\n* Active infection requiring systemic therapy, known HIV infection, or positive test for hepatitis B surface antigen or hepatitis C (antibody screen and if positive confirmed by RNA analysis). If positive results are not indicative of a true active or chronic infection, the patient can be enrolled after discussion with and agreement by the Investigator.\n* Any other acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into the trial.\n* Evidence of acute or chronic infection on screening chest radiography.","99 Years",{"count":471,"type":19},30,[258],"This research study is being done to find out if the immunotherapy drugs called CDX-301 and CDX-1140 in combination with the standard chemotherapy treatment pegylated liposomal doxorubicin (PLD, Doxil) are safe and effective at controlling the cancer in patients with metastatic triple Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer, and to determine a safe dose and treatment schedule of the three drugs. This research study will also test how your immune system responds to these treatments alone and in combination.",[240,25],{"date":370,"type":32},{"date":477,"type":32},"2022-04-20",{"date":479,"type":19},"2029-04-20",{"name":481,"class":39},"University of Texas Southwestern Medical Center",7,{"id":484,"slug":4,"hasResults":11,"nctId":485,"briefTitle":486,"officialTitle":487,"acronym":488,"eligibilityCriteria":489,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":490,"targetDuration":4,"studyType":20,"phases":492,"briefSummary":493,"conditions":494,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":454,"lastUpdatePostDateStruct":495,"startDateStruct":496,"completionDateStruct":498,"leadSponsor":500,"locationsCount":501},"100318305","NCT03424005","A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer","A Phase Ib\u002FII, Open-label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic Breast Cancer (Morpheus-panBC)","Morpheus-panBC","Inclusion Criteria\n\nPatients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and to qualify for Stage 2 (2L CIT-naïve cohort):\n\n* Age \\>\u002F= 18 years at the time of signing Informed Consent Form\n* Eastern cooperative oncology group (ECOG) performance status of 0 or 1\n* Able to comply with the study protocol, in the investigator's judgment\n* Metastatic or inoperable locally advanced adenocarcinoma of the breast\n* Measurable disease (at least one target lesion) according to RECIST v1.1\n* Life expectancy \\>\u002F= 3 months, as determined by the investigator\n* Tumor accessible for biopsy, unless archival tissue is available\n* Availability of a representative tumor specimen that is suitable for biomarker analysis via central testing\n* Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment\n* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs, as outlined for each specific treatment arm\n* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm\n\nExclusion Criteria\n\nExclusion Criteria for Stage 1\n\n* Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40 agonists or interleukin-2 (IL-2) or IL-2-like compounds\n* Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment\n* Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study\n* Eligibility only for the control arm\n\nExclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort)\n\n* Adverse events from prior anti-cancer therapy that have not resolved to Grade \\\u003C\u002F= 1 or better with the exception of alopecia of any grade and Grade \\\u003C\u002F= 2 peripheral neuropathy\n* Treatment with investigational therapy within 28 days prior to initiation of study treatment\n* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)\n* Uncontrolled tumor-related pain\n* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases\n* History of leptomeningeal disease\n* Active or history of autoimmune disease or immune deficiency\n* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.\n* Active tuberculosis\n* Severe infection within 4 weeks prior to initiation of study treatment\n* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment\n* Significant cardiovascular disease\n* Prior allogeneic stem cell or solid organ transplantation\n* History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death\n* Pregnancy or breastfeeding, or intention of becoming pregnant during the study",{"count":491,"type":19},1132,[258,50],"This is an umbrella study evaluating the efficacy and safety of multiple treatment combinations in participants with metastatic or inoperable locally advanced breast cancer.\n\nThe study will be performed in two stages. During Stage 1, seven cohorts will be enrolled in parallel in this study:\n\nCohort 1 will consist of programmed death-ligand 1 (PD-L1)-positive participants who have received no prior systemic therapy for metastatic or inoperable locally advanced triple-negative breast cancer (TNBC) (first-line \\[1L\\] PD-L1+ cohort).\n\nCohort 2 will consist of participants who had disease progression during or following 1L treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not received cancer immunotherapy (CIT) (second-line \\[2L\\] CIT-naïve cohort).\n\nCohort 3, 5, 6 and 7 will consist of participants with locally advanced or metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative disease with one or more PIK3CA mutations.\n\nCohort 4 will consist of participants with locally advanced or metastatic HER2+ \u002FHER2-low disease with one or more PIK3CA mutations who had disease progression on standard-of-care therapies (HER2+ \u002FHER2-low cohort).\n\nIn each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). During Stage 2, participants in the 2L CIT-naïve cohort who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment combination, provided Stage 2 is open for enrollment and all eligibility criteria are met.",[25],{"date":370,"type":32},{"date":497,"type":32},"2018-03-30",{"date":499,"type":19},"2030-09-30",{"name":172,"class":128},46,{"id":503,"slug":4,"hasResults":11,"nctId":504,"briefTitle":505,"officialTitle":506,"acronym":507,"eligibilityCriteria":508,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":509,"targetDuration":4,"studyType":20,"phases":510,"briefSummary":511,"conditions":512,"keywords":515,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":529,"lastUpdatePostDateStruct":530,"startDateStruct":531,"completionDateStruct":533,"leadSponsor":535,"locationsCount":537},"100599536","NCT07085767","Palazestrant in Combination With Ribociclib for the First-line Treatment of ER+\u002FHER2- Advanced Breast Cancer","A Phase 3 Randomized, Double-Blind, Active-Controlled Study of Palazestrant With Ribociclib Versus Letrozole With Ribociclib for the First-Line Treatment of ER+, HER2- Advanced Breast Cancer (OPERA-02)","OPERA-02","Inclusion Criteria:\n\n* Adult female or male participants.\n* ER+, HER2- locally advanced or metastatic breast cancer that is not amenable to curative therapy.\n* Evaluable disease (measurable disease per RECIST 1.1 or bone-only disease).\n* De novo advanced breast cancer or with disease recurrence occurring after 12 months of completing adjuvant endocrine therapy (with or without CDK4\u002F6 inhibitors)\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n* Adequate hematologic, hepatic, and renal functions.\n* Female participants can be pre-, peri- or postmenopausal.\n* Male and pre- or peri-menopausal female participants must be willing to take a GnRH (or LHRH) agonist.\n\nExclusion Criteria:\n\n* Disease recurrence during adjuvant endocrine therapy\n* Currently receiving or previously received systemic anti-cancer therapy for ER+, HER2- advanced breast cancer.\n* Previously received treatment with fulvestrant, elacestrant or an investigational endocrine therapy in any setting.\n* History of allergic reactions to study treatment.\n* Any contraindications to letrozole and ribociclib.\n* Symptomatic central nervous system metastases, carcinomatous meningitis, leptomeningeal disease, or a spinal cord compression that require immediate treatment.",{"count":448,"type":19},[140],"This phase 3 clinical trial compares the efficacy and safety of palazestrant with ribociclib to letrozole and ribociclib in women and men who have not received prior systemic anti-cancer treatment for advanced breast cancer.",[239,285,25,513,514],"ER Positive Breast Cancer","HER2 Negative Breast Carcinoma",[516,517,518,519,520,521,522,523,524,525,526,527,528],"Randomized","Multicenter","Double-Blind","Active-Controlled","Phase 3","Palazestrant","Complete Estrogen Receptor Antagonist (CERAN)","Selective Estrogen Receptor Degrader (SERD)","Ribociclib","CDK4\u002F6i","Letrozole","Aromatase inhibitors","Antineoplastic agents","2026-06-12",{"date":431,"type":32},{"date":532,"type":32},"2025-11-03",{"date":534,"type":19},"2032-01",{"name":536,"class":128},"Olema Pharmaceuticals, Inc.",150,{"id":539,"slug":4,"hasResults":11,"nctId":540,"briefTitle":541,"officialTitle":542,"acronym":543,"eligibilityCriteria":544,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":545,"targetDuration":4,"studyType":75,"phases":4,"briefSummary":546,"conditions":547,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":548,"lastUpdatePostDateStruct":549,"startDateStruct":550,"completionDateStruct":552,"leadSponsor":554,"locationsCount":555},"100619667","NCT07347600","A Study to Evaluate the Effectiveness and Safety of Inavolisib in Participants With Endocrine-resistant, PIK3CA-mutated, Hormone Receptor-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer","A Non-interventional Study to Evaluate the Effectiveness and Safety of Inavolisib in Patients With Endocrine-resistant, PIK3CA-mutated, Hormone Receptor-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer (reaINAVO)","reaINAVO","Inclusion Criteria:\n\n* Participants must be diagnosed with endocrine-resistant, PIK3CA-mutated, HR+\u002FHER2- LA\u002FmBC, following recurrence on or after completing adjuvant endocrine therapy\n* Participants must receive the treatment of inavolisib for the first time\n* PIK3CA mutation status should be detected by a National Medical Products Administration (NMPA)-approved or validated assay \\[Polymerase Chain Reaction (PCR) or Next Generation Sequencing (NGS)\\] by testing of blood or tumor tissue prior to the initiation of inavolisib\n\nExclusion Criteria:\n\n* Participants for which the treatment with inavolisib is not indicated per prescribing information. If the participant starts palbociclib and fulvestrant first, and starts inavolisib after getting a PIK3CA mutation-positive test result later, the palbociclib and fulvestrant will not be deemed as a different line of therapy. However, the medical order of PIK3CA mutation test must be made before or at the same time with the prescription of palbociclib and fulvestrant\n* Participants not receiving treatment for LA\u002FmBC with inavolisib according to standard of care (SOC) and in line with the current summary of product characteristics (SPC)\u002Flocal labeling\n* At the investigator's discretion, any reason that makes the participant hard to follow up or unsuitable to participate in the study",{"count":138,"type":19},"The main purpose of this study is to evaluate the effectiveness of inavolisib based regimen in participants with endocrine-resistant, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA)-mutated, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer (LA\u002FmBC), following on or after completing adjuvant endocrine therapy in routine clinical practice in China.",[285,25],"2026-06-11",{"date":529,"type":32},{"date":551,"type":32},"2026-01-21",{"date":553,"type":19},"2029-09-09",{"name":172,"class":128},23,{"id":557,"slug":4,"hasResults":11,"nctId":558,"briefTitle":559,"officialTitle":560,"acronym":561,"eligibilityCriteria":562,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":563,"targetDuration":4,"studyType":20,"phases":565,"briefSummary":566,"conditions":567,"keywords":574,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":581,"lastUpdatePostDateStruct":582,"startDateStruct":583,"completionDateStruct":585,"leadSponsor":587,"locationsCount":40},"100610025","NCT07222215","PhII Randomized CAPecitabine + ELAcestrant vs. Capecitabine Alone in ER+ Breast Cancer (CAPELA)","A Phase II Multi-Center Open-label Randomized Study of CAPecitabine in Combination With ELAcestrant Versus Capecitabine Alone in Advanced Estrogen Receptor-Positive Breast Cancer (CAPELA)","CAPELA","Inclusion Criteria:\n\n* Participants must have histologically confirmed estrogen receptor-positive (ER+), HER2-negative metastatic or locally recurrent unresectable (advanced) invasive breast cancer. ER and HER2 measurements should be performed according to institutional guidelines in a CLIA-approved setting. ER must be ≥ 10% on the most recent biopsy in which receptor testing was performed. Cutoff values for positive\u002Fnegative HER2 staining should be in accordance with current ASCO\u002FCAP (American Society of Clinical Oncology\u002FCollege of American Pathologists) guidelines.\n* Participants must have standard of care ctDNA sequencing testing documenting ESR1 and TP53 mutation status. In patients without ESR1 mutation, this result must be from within 3 months.\n\n  * ESR1 mutations that are considered pathogenic are: E380Q, V422del, S436P, L536H, L536P, L536R, Y537C, Y537D, Y537N, Y537S, D538G\n  * TP53 mutations that are considered pathogenic as determined by a CLIA certified laboratory\n* Women or men age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of capecitabine in combination with elacestrant participants \\\u003C18 years of age are excluded from this study\n* Women must be postmenopausal, which is defined as any of the following:\n\n  * Age ≥ 60 years\n  * Age \\\u003C 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range\n  * Premenopausal women who have been on a GnRH agonist for at least three consecutive months prior to study entry are eligible. Women in this group MUST remain on the GnRH agonist for the duration of protocol treatment.\n  * Status-post bilateral oophorectomy or total hysterectomy after adequate healing post-surgery\n* Must have measurable or evaluable disease by RECIST 1.1. Must have progressed on at least one line of endocrine therapy in the metastatic setting or recurred on or within one year of adjuvant endocrine therapy\n* Unrestricted number of prior endocrine therapies (with or without targeted treatment) are allowed in the advanced disease setting. If a patient recurred on or within one year of adjuvant endocrine therapy, it would be counted as one line of treatment.\n* Prior CDK4\u002F6 inhibition is required (in adjuvant or metastatic disease), unless a CDK4\u002F6 inhibitor is contraindicated (CDK4\u002F6 inhibitor in combination with endocrine treatment is considered as one line of endocrine treatment).\n* Participants must have remained on a prior endocrine treatment alone or in combination with a CDK4\u002F6 inhibitor in the metastatic setting without progression for at least 6 months prior to study entry. This regimen does not need to be the most recent regimen prior to study entry. If patients have progressed on adjuvant endocrine treatment and have not received treatment in the metastatic setting, they must have progressed after at least two years of adjuvant endocrine treatments.\n* Prior alpelisib with endocrine treatment is allowed (considered as a line of endocrine treatment).\n* Prior everolimus with endocrine treatment is allowed (considered a line of endocrine treatment).\n* Prior capivasertib with endocrine treatment is allowed (considered a line of endocrine treatment)\n* Prior fulvestrant is permitted. Prior SERM (tamoxifen, lasofoxifene) is permitted. Neither prior oral SERDs nor other next generation oral endocrine therapies (such as PROTACS) are permitted.\n* No prior chemotherapy regimen or ADC is allowed in the metastatic setting.\n* Participants may have received radiotherapy for palliative purposes but must not be experiencing grade \\>1 treatment-related toxicities at study entry and must have completed treatment \\> 14 days prior to registration.\n* ECOG PS 0-1\n* Adequate hematological, liver, and kidney function, as defined below:\n\n  * Absolute neutrophil count \\> 1,500\u002FµL\n  * Platelets \\> 100,000\u002FµL\n  * Hemoglobin \\> 9 g\u002FdL (transfusion is allowed to meet this criterion) Total bilirubin \\\u003C 1.5 x institutional upper limit or normal (ULN) or \\\u003C 3 institutional ULN in the presence of documented Gilbert's syndrome\n  * AST (SGOT)\u002FALT (SGPT) \\\u003C 2.5 x institutional ULN, or ≤ 5 institutional ULN for subjects with documented metastatic disease to the liver\n  * Creatinine clearance \\> 50 mL\u002Fmin\u002F1.73 m2\n* Women of childbearing age, women who are made postmenopausal through use of GNRH agonists, and men must agree to use adequate contraception for the duration of protocol treatment and for at least 6 months after the last dose of capecitabine.\n* Premenopausal women must have a negative serum or urine pregnancy test. Pregnancy testing does not need to be pursued in female participants who are:\n\n  * Age \\> 60 years; or\n  * Age \\\u003C 60 with intact uterus and amenorrhea for 12 consecutive months or more AND estrogen (estradiol) and FSH levels are within postmenopausal range; or\n  * Status-post bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation\n* Participants must be able to swallow and retain oral medication.\n* Ability to understand and the willingness to sign a written informed consent document.\n* HIV-infected participants must have well-controlled HIV on ART, defined as:\n\n  1. Participants on ART must have a CD4+ T-cell count ≥350 cells\u002Fmm3 at the time of screening.\n  2. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening.\n  3. It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months.\n  4. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study. The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors\u002Finducers\u002Fsubstrates.\n\nNote: No HIV testing is required at screening unless mandated by local health Authority.\n\n* Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before allocation.\n\nNote: Participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.Hepatitis B screening tests are not required unless:\n\n* Known history of HBV infection\n* As mandated by local health authority Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.\n\nNote: Participants must have completed curative antiviral therapy at least 4 weeks before allocation.\n\nHepatitis C screening tests are not required unless:\n\n* Known history of HCV infection\n* As mandated by local health authority\n\nExclusion Criteria:\n\n* Participants who have had endocrine and\u002For biologic therapy \\\u003C 14 days prior to entering the study or those who have not recovered from any prior treatment-related toxicities (must recover to no more than grade 1; alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 toxicity not constituting a safety risk based on investigator's judgment are acceptable). This is to minimize risk of drug-drug interactions and clarify etiology of future toxicities.\n* Participants who are receiving concurrent therapy with other investigational agents. This is to minimize risk of drug-drug interactions and clarify etiology of future toxicities.\n* Rapidly progressive, symptomatic, visceral spread of disease placing participant at risk of life- threatening complications in the short term. It is likely that these patients will not benefit from this regimen.\n* History of dihydropyrimidine dehydrogenase (DPD) deficiency. Patients with this deficiency are prone to significant toxicity from capecitabine.\n* Participants with active brain metastases. Treated brain metastases that are asymptomatic and do not require systemic steroids for management of symptoms are allowed if they have received SRS (7-day washout) or WBRT (14-day washout) or asymptomatic untreated brain metastases measuring \\\u003C1cm. Patients with leptomeningeal disease are not eligible. It is unlikely that these patients will benefit from this regimen.\n* Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring systemic therapy, clinically significant cardiovascular disease including: cerebral vascular accident\u002Fstroke (\\\u003C 6 months prior to enrollment), myocardial infarction (\\\u003C 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication, uncontrolled diabetes mellitus, gastrointestinal disorders potentially affecting the absorption of elacestrant, inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or total gastric resection, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements. Active hepatitis B or active hepatitis C infection. Ability to comply with study requirements is to be assessed by each investigator at the time of screening for study participation. This could increase risk of toxicity from treatment and potentially decrease adherence to study protocol.\n* Individuals with a history of a different malignancy are ineligible except for the following circumstances:\n\n  * (1) Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. These cases should be discussed with the sponsor-investigator prior to enrollment.\n  * (2) Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast, cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. History of prior malignancy puts patients at risk of recurrence from their prior malignancy or progression of a second malignancy which would complicate interpretation of the end points of this trial.\n* Ongoing treatment with drugs that are sensitive substrates of P-glycoprotein (dabigatran, digoxin, fexofenadine) or BRCP (rosuvastatin, sulfasalazine). These drugs have potential drug-drug interactions with the study agents.\n* Treatment with strong CYP3A inhibitors within 2 weeks before first study treatment administration or five elimination half-lives, whichever is longest and cannot be replaced.\n* Medical conditions requiring concomitant administration of medications with a narrow therapeutic window metabolized by CYP3A and for which a dose reduction cannot be considered. See Appendix D for a list of medications that are CYP3A substrates. These drugs have potential drug-drug interactions with the study agents.\n* Female participants lactating or nursing. The safety of these medications in pregnancy or breast feeding patients is unknown.\n\nBoth men and women of all races and ethnic groups are eligible for this trial.",{"count":564,"type":19},297,[50],"The goal of this research study is to compare a combination of two drugs, capecitabine and elacestrant to capecitabine alone as a treatment for advanced estrogen receptor-positive (ER+) breast cancer. This study is designed for participants with cancer that has previously stopped responding to medication in the class of therapy called CDK 4\u002F6 inhibitors, including palbociclib, ribociclib, or abemaciclb.\n\nThe names of the study drugs involved in this study are:\n\n* Elacestrant (a type of selective estrogen receptor degrader)\n* Capecitabine (a type of fluoropyrimidine antimetabolite)",[53,25,239,568,569,570,571,572,573],"Hormone Receptor Positive Breast Cancer","Human Epidermal Growth Factor 2 Negative Carcinoma of Breast","HER2- Breast Cancer","ESR1 Gene Mutation","ER Wildtype","Breast Neoplasms",[575,25,576,577,578,570,579,580],"Advanced Estrogen Receptor-Positive Breast Cancer","Breast cancer","Hormone receptor positive breast cancer","Advanced Human Epidermal Growth Factor Receptor 2 negative breast cancer","ESR1 gene mutation","ER wildtype","2026-06-10",{"date":529,"type":32},{"date":584,"type":32},"2026-01-16",{"date":586,"type":19},"2030-10-01",{"name":588,"class":39},"Kristina A. Fanucci",{"id":590,"slug":4,"hasResults":11,"nctId":591,"briefTitle":592,"officialTitle":593,"acronym":594,"eligibilityCriteria":595,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":596,"targetDuration":4,"studyType":20,"phases":598,"briefSummary":599,"conditions":600,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":581,"lastUpdatePostDateStruct":604,"startDateStruct":605,"completionDateStruct":607,"leadSponsor":609,"locationsCount":173},"100591599","NCT06982521","Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+\u002FHER2- Breast Cancer","A Phase 3 Open-Label Randomized Study Assessing the Efficacy and Safety of RLY-2608 + Fulvestrant Versus Capivasertib + Fulvestrant as Treatment for PIK3CA-mutant Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+\u002FHER2-) Locally Advanced or Metastatic Breast Cancer Following Recurrence or Progression On or After Treatment With a CDK4\u002F6 Inhibitor","ReDiscover-2","Inclusion Criteria:\n\n* Patient has ECOG performance status of 0-1\n* One or more known primary oncogenic PIK3CA mutation(s)\n* Adult females, pre- and\u002For post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with a gonadotropin-releasing hormone (GnRH) agonist. Patients are to have commenced treatment with a GnRH agonist at least 4 weeks prior to randomization and must be willing to continue on it for the duration of the study.\n* Histologically or cytologically confirmed diagnosis of HR+\u002FHER2- locally advanced or metastatic breast cancer (ABC) with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent\n* Measurable disease per RECIST v1.1 or evaluable bone-only disease.\n* Must have radiological evidence of progression on or after previous treatment for HR+\u002FHER2- ABC with:\n\n  1. At least 1 and no more than 2 lines of endocrine therapy (ET) in the (neo)adjuvant setting with recurrence on or within 12 months of completion or in the ABC setting\n  2. 1 prior line of CDK4\u002F6 inhibitor therapy in one of the following settings:\n\n     1. CDK4\u002F6 inhibitor + ET in the ABC setting\n     2. CDK4\u002F6 inhibitor therapy in the adjuvant setting if progression occurred during or within 12 months of completion of adjuvant CDK4\u002F6 inhibitor with ET\n     3. Patients who progressed during or within 12 months of completion of adjuvant CDK4\u002F6 inhibitor and after receiving CDK4\u002F6 inhibitor therapy in the advanced setting are considered to have had \\>1 prior line of CDK4\u002F6 inhibitor and are not eligible\n\nExclusion Criteria:\n\n* Prior treatment with any of the following:\n\n  1. CDK2 or selective CDK4 inhibitors or any investigational therapies targeting cyclin dependent kinases\n  2. PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3\u002FAKT\u002FmTOR pathway\n  3. Immunotherapy\n  4. Antibody drug conjugates\n* Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥ 140 mg\u002FdL, or glycosylated hemoglobin (HbA1c) ≥7.0% (≥ 53 mmol\u002Fmol).\n* Clinically significant, uncontrolled cardiovascular disease\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events\n* Known active uncontrolled or symptomatic CNS metastases associated with progressive neurological symptoms or requiring ongoing corticosteroids or anticonvulsants for symptomatic control\n* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease\n* History of hypersensitivity to fulvestrant or drugs in a similar class as fulvestrant, RLY-2608, or capivasertib, including their excipients\n* Known activating AKT mutations, loss-of-function PTEN mutations, or loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K",{"count":597,"type":19},540,[140],"This is a global, multicenter, open-label, randomized Phase 3 study comparing the efficacy and safety of RLY-2608 + fulvestrant to capivasertib + fulvestrant for the treatment of patients with HR+\u002FHER2- ABC with PIK3CA mutation following recurrence or progression on or after treatment with a CDK4\u002F6 inhibitor.",[601,602,603,239,25,317],"PIK3CA Mutation","HER2- Negative Breast Cancer","Hormone Receptor Positive Tumor",{"date":548,"type":32},{"date":606,"type":32},"2025-08-26",{"date":608,"type":19},"2031-12-31",{"name":610,"class":128},"Relay Therapeutics, Inc.",{"id":612,"slug":4,"hasResults":11,"nctId":613,"briefTitle":614,"officialTitle":615,"acronym":616,"eligibilityCriteria":617,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":618,"targetDuration":4,"studyType":20,"phases":620,"briefSummary":622,"conditions":623,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":631,"lastUpdatePostDateStruct":632,"startDateStruct":633,"completionDateStruct":635,"leadSponsor":637,"locationsCount":40},"100643060","NCT07608848","First-in-human Diagnostic Imaging Profile of the Theranostic Pair [68Ga]Ga-DOTA-STR-17126 and Low Dose [177Lu] Lu-DOTA-STR-17126 in Patients With Advanced or Metastatic Cancer","An Open-label, First-in-human, Exploratory Imaging Study of the DOTA-STR-17126 Theranostic Pair [68Ga]Ga-DOTA-STR-17126 and Low-dose [177Lu]Lu-DOTA-STR-17126 in Patients With Advanced or Metastatic Cancer","DOTA-STR-17126","Inclusion Criteria:\n\nInclusion criteria refer to the enrolment of participants for the PET\u002FCT and SPECT\u002FCT imaging with the radioligands; PET imaging tracer \\[68Ga\\]Ga-DOTA-STR-17126 and with the SPECT imaging tracer \\[177Lu\\]Lu-DOTA-STR-17126. Participants must meet all of the following inclusion criteria to be eligible for enrolment.\n\n1. Ability to understand and willingness to provide informed consent\n2. Adults ≥ 18 years of age\n3. Must have the following histologically or cytologically confirmed diagnosis of advanced or metastatic i. breast cancer ii. prostate cancer\n4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1\n5. Participant must have clinical or radiological documented tumour progression as established by the Investigator within 30 days of signing consent for the study\n6. Participants who have exhausted standard-of-care systemic therapies in their metastatic setting. At least one detectable by conventional imaging tumour lesion with any diameter of ≥ 1 cm in size\n7. Participants must have adequate organ and bone marrow function, defined as follows:\n\n   i. Absolute neutrophil count (ANC) ≥ 1000 cells\u002Fmm3 ii. Platelet count ≥ 100,000\u002Fmm3 iii. Haemoglobin ≥ 9.0 g\u002FdL iv. AST, ALT, alkaline phosphatase ≤ 3 times upper limit of normal (ULN) if there is no evidence of liver metastases or ≤5 ULN in the presence of liver metastases v. Total bilirubin ≤ 2 times upper limit of normal (ULN) vi. Creatinine ≤ 2 times ULN and creatinine clearance (CrCL) ≥ 60mL\u002Fmin using the Cockcroft Gault equation (Appendix 2)\n8. Able to remain still for up to 60 minutes per scan\n9. Any other condition which, in the opinion of the Investigator, would preclude participation in this study Optional: Participants that have available archival tissue (at least 15 consecutive, unstained, formalin-fixed, paraffin embedded (FFPE) slides or 1 FFPE block), or a fresh tumour biopsy sample that opt to provide samples will be used for GRPR analysis (histology staining or RNA measurements). Participants without any archival tissue or fresh biopsy sample, or who refuse to provide archival tissue are still eligible for the study.\n\nExclusion Criteria:\n\nParticipants must not be enrolled into the trial if one or more of the following criteria are met. Participants must NOT meet any of the following Exclusion criteria to be eligible for enrolment:\n\n1. Known hypersensitivity to the investigational medicinal products (DOTA-STR-17126) or any of the excipients.\n2. Participants with Class 3 or 4 New York Heart Association (NYHA) Congestive Heart Failure.\n3. Average QTc (using the Fridericia correction calculation) \\> 470 msec for females and QTcF \\>450 msec for males on screening ECG or history of congenital long QT syndrome.\n4. Clinically significant bleeding within two weeks prior to trial entry (i.e., gastrointestinal bleeding, intracranial bleeding).\n5. Pregnant or lactating women. i. For female participants of childbearing potential or male participants with female partner of childbearing potential, who are not willing to practice highly effective contraception during the trial and for at least 6 months after \\[177Lu\\] Lu-DOTA-STR-17126 administration ii. Sexually active males must use a condom during intercourse while taking the drug and for 4 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Female partners of childbearing potential should use highly effective contraceptive methods during and up to 6 months after stopping treatment.\n6. Have any medical condition that impairs complete bladder emptying. Participants with permanent urinary indwelling catheter (IDC) or nephrostomy may be allowed to enrol on a case-by-case basis in discussion with Principal Investigator, if it is determined not to put the patient at an increased risk of adverse drug effects and\u002For interfere with the integrity of study outcome.\n7. Major surgery, defined as any surgical procedure that involves general anaesthesia and a significant incision (i.e., larger than what is required for placement of a central venous access, percutaneous feeding tube, or biopsy) within 30 days before study day 1 or anticipated surgery within the subsequent 43 days (6 weeks).\n8. Has an additional active malignancy requiring therapy within the past 2 years.\n9. History of another malignancy within 3 years before study enrolment. A subject with the following malignancies is allowed if considered cured or unlikely to recur within 3 years:\n\n   i. Carcinoma of the skin without melanomatous features ii. Curatively treated cervical carcinoma in situ iii. Bladder tumours considered superficial such as non-invasive (T1a) and carcinoma in situ (T1s), thyroid papillary cancer with prior treatment\n10. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy within 30 days prior to trial enrolment.\n11. Psychiatric illness\u002Fsocial situations that would interfere with compliance with study requirements.\n12. Cannot undergo PET\u002FCT scanning because of weight limits (350 lbs or 160 kg).\n13. Prior exposure to any other GRPR-targeting therapeutic agents.\n14. Prior treatment with any systemic anti-cancer therapy including chemotherapy, immunotherapy, biological therapy, radiation therapy, biologic, hormonal or herbal therapy, or any investigational therapy or investigational device, unless:\n\n    i. Standard of care or maintenance therapy such as, luteinizing hormone-releasing hormone (LHRH) or gonadotropin releasing hormone (GnRH) for patients with prostate cancer; selective estrogen receptor modulators or aromatase inhibitors or GnRH inhibitors for breast cancer, ii. Within more than 30 days of chemotherapy, herbal therapies and monoclonal antibodies, iii. Within more than 5 half-lives for biologic\u002Fnon-cytotoxic targeted agents, iv. Within more than 8 weeks prior radiation therapies External Beam Radiotherapy (EBRT) and\u002For Radioligand Therapy (RLT). Focal palliative radiotherapy given within 8 weeks prior to the low dose of \\[177Lu\\] Lu-DOTA-STR-17126 may be approved on a case-by-case basis, if it is determined not to put the participant at an increased risk of adverse drug effects and\u002For interfere with the integrity of study outcome, v. For participants who received radiotherapy (EBRT and\u002For RLT) more than 8 weeks prior to the low dose of 177Lu-DOTA-STR-17126, efforts should be made to calculate the prior radiation absorbed dose to each critical organ such as the kidneys, liver, lungs, and bone marrow.\n15. Patients with a history of inflammatory disease which according to the investigator may interfere with correct evaluation of radioactive uptake, especially those affecting the thoraco-abdominal cavities (i.e., autoimmune, granulomatous disease).\n16. Any clinically significant toxicity (with the exception of alopecia) related to prior anti-tumour therapy not resolved to Grade 1 or baseline.",{"count":619,"type":19},20,[621],"EARLY_PHASE1","This is an open-label, first-in-human, exploratory Phase 0 study evaluating the safety and diagnostic imaging performance of the DOTA-STR-17126 theranostic pair in patients with advanced or metastatic breast or prostate cancer. The study investigates \\[68Ga\\]Ga-DOTA-STR-17126 for PET imaging and, in patients with positive GRPR uptake, a low dose of \\[177Lu\\]Lu-DOTA-STR-17126 for SPECT imaging and dosimetry.\n\nThe primary objective is to assess safety and tolerability. Secondary objectives include evaluation of imaging quality, biodistribution, pharmacokinetics, and radiation dosimetry. Exploratory objectives assess correlations between GRPR expression in tumour tissue and imaging uptake.\n\nThe study is conducted at a single centre in Australia, with 12 evaluable participants (up to 20 enrolled), and supports the development of a GRPR-targeted theranostic approach for personalised cancer management.",[25,624,625,626,627,628,629,630],"Metastatic Prostate Cancer","GRPR-Targeted Molecular Imaging","Theranostic Radiopharmaceuticals","Cancer","Active Cancer","Theranostic","Radiopharmaceutical","2026-06-08",{"date":581,"type":32},{"date":634,"type":32},"2026-05-28",{"date":636,"type":19},"2029-05-31",{"name":638,"class":39},"Integrated Haematology and Oncology Network",""]