[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100584747":3},{"organization":4,"outcomesModule":7,"designInfo":57,"detailedDescription":61,"studyPopulation":62,"armGroups":63,"interventions":69,"overallOfficials":75,"centralContacts":80,"locations":85,"responsibleParty":104,"collaborators":58,"id":105,"slug":58,"hasResults":106,"nctId":107,"briefTitle":108,"officialTitle":109,"acronym":110,"eligibilityCriteria":111,"healthyVolunteers":106,"sex":112,"minAge":113,"maxAge":58,"enrollmentInfo":114,"targetDuration":117,"studyType":118,"phases":58,"briefSummary":119,"conditions":120,"keywords":58,"overallStatus":88,"whyStopped":58,"lastUpdateSubmitDate":123,"lastUpdatePostDateStruct":124,"startDateStruct":127,"completionDateStruct":129,"leadSponsor":131,"locationsCount":132},{"fullName":5,"class":6},"CHA University","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":37},[9],{"measure":10,"description":11,"timeFrame":12},"Objective Response Rate (ORR)","The proportion of patients who achieve a complete response (CR) or partial response (PR) according to RECIST v1.1.","Up to 24 months after treatment initiation.",[14,18,21,24,27,30,33],{"measure":15,"description":16,"timeFrame":17},"Overall Survival (OS)","Time from the date of first dose to the date of death from any cause.","Up to 36 months after treatment initiation.",{"measure":19,"description":20,"timeFrame":12},"Progression-Free Survival (PFS)","Time from the date of first dose to disease progression per RECIST v1.1 or death from any cause.",{"measure":22,"description":23,"timeFrame":12},"Disease Control Rate (DCR)","The proportion of patients who achieve complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1.",{"measure":25,"description":26,"timeFrame":12},"Duration of Response (DOR)","Time from first documented response (CR or PR) to progression or death.",{"measure":28,"description":29,"timeFrame":12},"Quality of Life (QoL)- EORTC QLQ-C30","Patient-reported quality of life assessed using the EORTC QLQ-C30 questionnaire.",{"measure":31,"description":32,"timeFrame":12},"Quality of Life (QoL)- EORTC QLQ-BIL21","Patient-reported quality of life assessed using the EORTC QLQ-BIL21 questionnaire.",{"measure":34,"description":35,"timeFrame":36},"Safety and Tolerability","Incidence, severity, and type of adverse events (AEs), graded per NCI CTCAE v5.0.","Up to 30 days after last dose.",[38,42,46,50,54],{"measure":39,"description":40,"timeFrame":41},"Immune System Response and Immunomodulation Markers","Changes in immune system markers in peripheral blood and tumor tissue samples, including:\n\nCD8+ T-cell count (%) PD-L1 expression levels in tumor tissues Cytokine levels (e.g., IFN-γ, IL-6, TNF-α) T-cell receptor (TCR) clonality","Baseline, during treatment (every 3 cycles; each cycle = 21 days), and at progression (up to 24 months)",{"measure":43,"description":44,"timeFrame":45},"Metabolic Biomarker Changes in Peripheral Blood and Tumor Tissues","Changes in metabolic biomarkers in peripheral blood and tumor tissue samples, including:\n\nSerum glucose levels (mg\u002FdL) and insulin resistance markers (e.g., HOMA-IR) Lipid metabolism markers (e.g., triglycerides, total cholesterol, LDL, HDL) Lactate and pyruvate levels as indicators of altered tumor metabolism Amino acid profiling (e.g., glutamine, alanine) for metabolic reprogramming","Baseline, during treatment, and at progression (up to 24 months)",{"measure":47,"description":48,"timeFrame":49},"Collection and Storage of DNA and RNA for Future Exploratory Study","To collect and store DNA and RNA (following ethical guidelines) for future exploratory research investigating genetic variations that may affect responses to study treatment (distribution, safety, tolerability, and efficacy) and\u002For susceptibility to diseases. Participation in this exploratory study is optional.","Baseline and during treatment (up to 24 months)",{"measure":51,"description":52,"timeFrame":53},"Quality of Life (QoL) - EORTC QLQ-C30","Patient-reported quality of life assessed using the EORTC QLQ-C30 questionnaire, which evaluates physical, emotional, cognitive, and social functioning.","Baseline, every 3 cycles during treatment (each cycle = 21 days), and at the end of treatment (up to 24 months)",{"measure":55,"description":56,"timeFrame":53},"Quality of Life (QoL) - EORTC QLQ-BIL21","Patient-reported quality of life specific to biliary tract cancer, assessed using the EORTC QLQ-BIL21 questionnaire, which measures biliary cancer-related symptoms such as jaundice, pain, and fatigue",{"allocation":58,"interventionModel":58,"interventionModelDescription":58,"primaryPurpose":58,"observationalModel":59,"timePerspective":60,"maskingInfo":58},null,"COHORT","PROSPECTIVE","Biliary tract cancer (BTC) is a heterogeneous group of malignancies arising from the biliary epithelium, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. Most patients are diagnosed at unresectable, locally advanced, or metastatic stages, and the prognosis remains poor despite advances in systemic therapy.\n\nSince the ABC-02 trial established Gemcitabine plus Cisplatin as the standard first-line chemotherapy for advanced BTC, numerous combination strategies have been explored to improve survival outcomes. In particular, the addition of Nab-paclitaxel to Gemcitabine and Cisplatin has shown promising efficacy by enhancing stromal penetration and drug delivery, supported by preclinical and early clinical studies.\n\nMore recently, immune checkpoint inhibitors (ICIs) have emerged as a new treatment option for BTC. The TOPAZ-1 trial demonstrated that adding Durvalumab to Gemcitabine and Cisplatin significantly improved Overall Survival (OS), establishing immunotherapy-based combination therapy as a new standard of care for advanced BTC. Similarly, the KEYNOTE-966 trial confirmed the benefit of Pembrolizumab combined with Gemcitabine and Cisplatin, further supporting the role of ICIs in BTC management.\n\nTislelizumab, a humanized PD-1 monoclonal antibody, has shown efficacy in various solid tumors and is now being evaluated in BTC. Compared to other PD-1 inhibitors, Tislelizumab was designed to minimize Fc receptor binding, potentially reducing off-target immune activation and enhancing anti-tumor immune response. Combining Tislelizumab with cytotoxic chemotherapy, including Nab-paclitaxel, may offer synergistic benefits by enhancing antigen release and promoting immune response within the tumor microenvironment.\n\nThis Phase 1b\u002F2 multicenter trial aims to investigate the safety, tolerability, and efficacy of the combination regimen of Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab in treatment-naïve patients with unresectable, locally advanced, or metastatic BTC. The study will be conducted across three medical centers in South Korea: CHA Bundang Medical Center, Haeundae Paik Hospital, and Seoul National University Bundang Hospital.\n\nThe Phase 1b part will determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Nab-paclitaxel when combined with Gemcitabine, Cisplatin, and Tislelizumab. Dose escalation will follow a standard 3+3 design, with dose-limiting toxicities (DLTs) assessed during Cycle 1.\n\nIn the Phase 2 part, the primary endpoint will be Objective Response Rate (ORR), with secondary endpoints including Overall Survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DOR), and Quality of Life (QoL) assessed using EORTC QLQ-C30 and QLQ-BIL21. Safety and tolerability will also be evaluated throughout the study.\n\nThis study seeks to optimize the therapeutic potential of chemotherapy plus immunotherapy by incorporating Nab-paclitaxel at a reduced dose to enhance tolerability while maintaining efficacy. Exploratory objectives include assessing immunological and metabolic changes induced by the study drugs, as well as collecting tumor and blood samples for future biomarker analyses.\n\nThrough this trial, we aim to establish a novel first-line treatment strategy for advanced BTC, potentially improving survival outcomes beyond the current standard of care.","Patients with unresectable, locally advanced, or metastatic biliary tract cancer (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer, who have not received prior systemic therapy for advanced disease.",[64],{"label":65,"type":58,"description":66,"interventionNames":67},"Combination Therapy Group","This group consists of patients with unresectable, locally advanced, or metastatic biliary tract cancer who will receive combination therapy with Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.",[68],"Drug: Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.",[70],{"type":71,"name":72,"description":73,"armGroupLabels":74,"otherNames":58},"DRUG","Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab.","Tislelizumab: IV 200mg on Day 1 of every 3-week cycle Nab-paclitaxel: IV 75mg\u002Fm2 on Days 1 and 8 of every 3-week cycle (up to 16 cycles) Gemcitabine: IV 800mg\u002Fm2 on Days 1 and 8 of every 3-week cycle Cisplatin: IV 25mg\u002Fm2 on Days 1 and 8 of every 3-week cycle (up to 8 cycles)",[65],[76],{"name":77,"affiliation":78,"role":79},"Hong Jae Chon, MD. PhD","Principal Investigator","PRINCIPAL_INVESTIGATOR",[81],{"name":77,"role":82,"phone":83,"phoneExt":58,"email":84},"CONTACT","82-31-780-3928","minidoctor@cha.ac.kr",[86],{"facility":87,"status":88,"city":89,"state":90,"zip":91,"country":92,"countryCode":58,"cosmosGeoPoint":93,"geoPoint":98,"contacts":99},"CHA Bundang Medical Center","RECRUITING","Seongnam-si","Gyeonggi-do","13496","South Korea",{"type":94,"coordinates":95},"Point",[96,97],127.13778,37.43861,{"lat":97,"lon":96},[100,102],{"name":77,"role":82,"phone":101,"phoneExt":58,"email":84},"82-31-780-3430",{"name":103,"role":79,"phone":58,"phoneExt":58,"email":58},"Hong Jae Chon",{"type":79,"investigatorFullName":103,"investigatorTitle":78,"investigatorAffiliation":5,"oldNameTitle":58,"oldOrganization":58},"100584747",false,"NCT06893380","Combination Therapy of GCNT and Tislelizumab in Advanced Biliary Tract Cancer","A Multicenter Phase 1b\u002F2 Trial Investigating the Efficacy and Toxicity of the Combination of Gemcitabine, Cisplatin, Nab-Paclitaxel, and Tislelizumab in Treatment Naïve Patients With Unresectable, Locally Advanced, or Metastatic BTC","GENTIS","Inclusion Criteria\n\n* Histologically confirmed biliary tract cancer (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer (excluding neuroendocrine tumors, sarcoma, mixed cholangiocarcinoma-HCC, and ampullary carcinoma).\n* Age ≥ 19 years at the time of signing informed consent.\n* Treatment-naïve for unresectable or metastatic BTC, or recurrence\u002Fmetastasis at least 6 months after curative surgery or adjuvant chemotherapy.\n* Measurable lesions per RECIST v1.1.\n* ECOG Performance Status (PS) of 0-1 within 14 days prior to the first dose.\n* Life expectancy of ≥ 3 months.\n* Adequate organ function (within 14 days prior to the first dose):\n\n  * Hematologic function: Hemoglobin (Hb) ≥ 9.0 g\u002FdL, Absolute neutrophil count (ANC) ≥ 1,500\u002FμL, Platelet count ≥ 100,000\u002FμL\n  * Renal function: Serum creatinine ≤ 1.5 × ULN or CrCl (Cockcroft-Gault) ≥ 45 mL\u002Fmin\n  * Hepatic function: AST and ALT ≤ 3.0 × ULN (≤ 5.0 × ULN for hepatic metastases), Total bilirubin ≤ 1.5 × ULN\n  * Coagulation: INR ≤ 1.5 or prothrombin time ≤ 1.5 × ULN, aPTT ≤ 1.5 × ULN\n* Reproductive status:\n\n  * Female participants must provide proof of non-childbearing status or a negative serum pregnancy test within 7 days before the first dose.\n  * Female subjects receiving cisplatin must agree to effective contraception for 14 months after the last dose; male subjects must agree for 11 months.\n  * Women of childbearing potential and non-sterilized men must use at least two effective contraceptive methods during the study and for 6 months after the last dose.\n* Cardiac function:\n\n  * Left ventricular ejection fraction (LVEF) ≥ 50% (by echocardiography or MUGA scan)\n  * No serious valvular disorders or arrhythmias\n  * Corrected QT interval ≤ 470 msec at screening\n* Willingness to provide tumor tissue samples by biopsy (endoscopic or excisional).\n\nExclusion Criteria\n\n* Prior treatment history:\n\n  * Prior systemic chemotherapy, biological therapy, immunotherapy, or hormone therapy for unresectable or metastatic BTC\n  * Prior adjuvant chemotherapy or radiation therapy within 6 months before recurrence\n* History of another malignancy within 5 years, except:\n\n  * Completely resected basal cell carcinoma, stage 1 squamous cell carcinoma, carcinoma in situ, or superficial bladder cancer\n* Unresolved toxicities from prior treatment that could affect study evaluation\n* Known hypersensitivity to any study drug (tislelizumab, gemcitabine, cisplatin, nab-paclitaxel)\n* Active or history of autoimmune disease, except:\n\n  * Hypothyroidism (on stable hormone therapy), vitiligo, or psoriasis not requiring treatment\n* History of interstitial lung disease, pulmonary fibrosis, or radiation pneumonitis\n* Active gastrointestinal disease:\n\n  * Active peptic ulcer, colitis, or diverticulitis Known central nervous system (CNS) metastasis\n* Uncontrolled tumor-related complications: Pericardial effusion, pleural effusion, or ascites requiring intervention, Uncontrolled tumor-related pain\n* Significant cardiovascular conditions:\n\n  * Myocardial infarction within 180 days before enrollment\n  * Uncontrolled angina within 180 days before enrollment\n  * NYHA Class III or IV congestive heart failure\n  * Persistent hypertension ≥ 150\u002F90 mmHg despite treatment\n  * Arrhythmias requiring medical intervention\n  * Thrombosis or vascular diseases requiring surgery\n* Uncontrolled diabetes mellitus\n* Active infections requiring systemic treatment within 14 days before the first dose\n* Recent treatment history:\n\n  * Systemic corticosteroids (except prophylactic or short-term use) or immunosuppressants within 28 days before the first dose\n  * Antitumor therapy (cytotoxic, targeted, or immunotherapy) within 28 days before the first dose\n  * Pleurodesis within 28 days before the first dose\n  * Major surgery under general anesthesia within 28 days before the first dose\n  * Local anesthesia or minor surgery within 14 days before the first dose\n  * Radiation therapy within 28 days before the first dose (bone metastasis radiation within 14 days is allowed)\n* Positive for:\n\n  * HIV-1 or HIV-2\n  * Active Hepatitis B or C (except HBV DNA \\\u003C500 IU\u002FmL with stable antiviral therapy)\n* Pregnant or breastfeeding women\n* Use of unapproved drugs within 28 days before enrollment\n* Cognitive impairment preventing informed consent\n* Severe neuropathy (Grade ≥ 2, CTCAE v5.0)\n* Hearing impairment\n* Inability or unwillingness to provide informed consent","ALL","19 Years",{"count":115,"type":116},61,"ESTIMATED","2 Years","OBSERVATIONAL","This is a multicenter Phase 1b\u002F2 clinical trial investigating the efficacy and safety of a combination regimen of Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab in treatment-naïve patients with unresectable, locally advanced, or metastatic biliary tract cancers (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.\n\nThe Phase 1b portion aims to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of Nab-paclitaxel in combination with Gemcitabine, Cisplatin, and Tislelizumab. In the Phase 2 portion, the study will evaluate the Objective Response Rate (ORR) as the primary endpoint, with additional assessments of Overall Survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR), and Quality of Life (QoL). Safety and tolerability will also be closely monitored.\n\nThis study seeks to leverage the stromal-disrupting effect of Nab-paclitaxel and the immune checkpoint blockade effect of Tislelizumab, combined with the established chemotherapy backbone of Gemcitabine and Cisplatin, to enhance treatment outcomes for BTC patients. The study will enroll patients across three medical centers in South Korea, including CHA Bundang Medical Center, Haeundae Paik Hospital, and Seoul National University Bundang Hospital.",[121,122],"Locally Advanced Biliary Tract Cancers","Metastatic Biliary Tract Cancers","2025-09-09",{"date":125,"type":126},"2025-09-15","ACTUAL",{"date":128,"type":126},"2024-10-01",{"date":130,"type":116},"2026-12-31",{"name":5,"class":6},1]