GEMCITABINE for Advanced biliary tract carcinoma

Inclusion criteria

• {"criterion_text":"- Signed and dated informed consent\n- Documented virology status of hepatitis, as confirmed by screening HBV and HCV tests\n- Patient affiliated to or beneficiary of French social security system\n- Ability to comply with the study protocol, in the Investigator’s judgment\n- Histologically confirmed biliary tract carcinoma: intra/extrahepatic cholangiocarcinoma (note that gallbladder carcinoma are not eligible)\n- Locally advanced, metastatic, or unresectable disease\n- Patient who had not previously received systemic anti-cancer treatment (adjuvant treatment with Capecitabine is allowed if the end of the chemotherapy was at least 6 months ago)\n- Age ≥ 18 years\n- Measurable disease defined according to RECIST v1.1 guidelines (Annex 2) Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.\n- Patients who have received previous chemoembolization, radioembolization and/or radiotherapy should have recovered from any treatment related toxicity, to a level of ≤ grade 1 according to National Cancer Institute [NCI] common terminology criteria for adverse events, version 5 (CTCAE v5) (Annex 5); with the exception of Grade 2 alopecia\n- Performance status ECOG-PS < 2\n- Females must be using highly effective contraceptive measures, and have a negative pregnancy test prior to the start of dosing if of childbearing potential, or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening"}

Exclusion criteria

• {"criterion_text":"- Patients previously exposed to anti-tumor immunotherapy such as anti-PD-1, anti-PD-L1, or anti-CTLA4 agent or any immune therapy\n- Uncontrolled pleural effusion, pericardial effusion, ascites or symptomatic fistula\n- Uncontrolled tumor-related pain: exposing patients to risk of exposure to corticoids or iterative hospitalizations. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to inclusion. Patients should be recovered from the effects of radiation. There is no required minimum recovery period\n- Inadequate organ functions: known cardiac failure of unstable coronaropathy, respiratory failure, or uncontrolled infection or another life-risk condition. Patients requiring oxygen therapy or with LEVF<40%.\n- HIV positive (HIV 1/2 antibodies patients), or a known history of active Tuberculosis bacillus\n- Any immunosuppressive therapy (i.e. corticosteroids >10 mg of hydrocortisone or equivalent dose) within 14 days before the planned start of study therapy\n- Active autoimmune disease that has required a systemic treatment in the past 2 years (i.e. corticosteroids or immunosuppressive drugs).\n- Prior allogeneic bone marrow transplantation or prior solid organ transplantation\n- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins\n- Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of durvalumab\n- Receipt of a live, attenuated vaccine within 30 days prior to inclusion or anticipation that such a live, attenuated vaccine will be required during the study\n- Known active central nervous system metastases and/or carcinomatous meningitis\n- Inadequate hematology function: Lymphocyte count at baseline < 700/mm3; neutrophil count < 1 500/mm3, platelets < 10 0000/mm3 (without transfusion), Hemoglobin < 9g/dL (patients may be transfused to meet this criterion).\n- Inadequate hepatic function: bilirubin >2 fold ULN, AST/ALT >3 fold ULN, International normalized thromboplastin time ratio >2\n- Creatinine clearance (CrCl) < 60 ml/min (by the Modification of Diet in Renal Disease [MDRD], Cockroft formula, or chronic kidney disease [CKD] formula])\n- Serum albumin < 28 g/L\n- History of angiocholitis, liver abscess, or acute pancreatitis within 4 weeks prior to initiation of study treatment\n- Diagnosis of additional malignancy within 3 years prior to the inclusion with the exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer\n- Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study\n- Current participation in a study of an investigational agent or in the period of exclusion\n- Patient under guardianship, curatorship or under the protection of justice\n- Other liver malignancy: hepatocellular carcinoma and hepato-cholangiocarcinoma\n- Cholangiocarcinoma displaying IDH1 mutations, FGFR2 fusions, BRAF mutations or HER2 amplification"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is the progression free survival status (PFS) at 12 months from the date of randomization evaluated by RECIST criteria v1.1.","definition_or_measurement_approach":"Progression free survival status at 12 months from randomization evaluated by RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- Dose limiting toxicity (DLT) evaluated with NCI-CTCAE criteria","definition_or_measurement_approach":"DLT evaluated according to NCI-CTCAE criteria (version 5)."}
• {"endpoint_text":"- Progression free survival status (PFS) at 12 months from the date of randomization evaluated by RECIST criteria v1.1.","definition_or_measurement_approach":"PFS at 12 months evaluated by RECIST v1.1."}
• {"endpoint_text":"- The PFS evaluated by RECIST criteria v1.1. Progression-free survival (PFS): defined as the delay from the date of randomization to the disease progression or death from any cause whichever occurs first. Alive patient without progression will be censored at last radiological evaluation available showing no progression.","definition_or_measurement_approach":"PFS defined as time from randomization to disease progression or death; censoring at last radiological evaluation showing no progression; assessed by RECIST v1.1."}
• {"endpoint_text":"- Overall survival (OS): defined as the delay from the date of randomization to death from any cause. Alive patient will be censored at last date known to be alive.","definition_or_measurement_approach":"OS defined as time from randomization to death from any cause; alive patients censored at last known alive date."}
• {"endpoint_text":"- Objective Response Rate (ORR): defined as the addition of complete response (CR) and partial response (PR) rates, evaluated by RECIST criteria v1.1. Disease control rate (DCR): defined as the addition of complete response (CR), partial response (PR), and stable disease (SD) rates, evaluated by RECIST criteria v1.1","definition_or_measurement_approach":"ORR = CR + PR rates by RECIST v1.1; DCR = CR + PR + SD rates by RECIST v1.1."}
• {"endpoint_text":"- Health related quality of life: EORTC-QLQ-C30 + EORTC QLQ – BIL21","definition_or_measurement_approach":"Patient-reported HRQoL measured with EORTC-QLQ-C30 and EORTC QLQ-BIL21 questionnaires."}
• {"endpoint_text":"- Toxicities graded according to NCI-CTCAE criteria version 5","definition_or_measurement_approach":"Adverse events graded per NCI-CTCAE v5."}
• {"endpoint_text":"- Tumor related biomarkers","definition_or_measurement_approach":"Tumor biomarkers assessed (details in protocol); includes immunohistochemistry and other assays as specified."}
• {"endpoint_text":"- On PBMC","definition_or_measurement_approach":"Analyses performed on peripheral blood mononuclear cells (PBMC) to assess immune contexture before and after treatment."}
• {"endpoint_text":"- \tPD-L1/FAP/CD40 expression on tumor and immune cells will be determined by immunohistochemistry at baseline, as well as presence of Tertiary lymphoid structures (CD3/CD8/CD20 and CD68/SSP1/CXCL9)","definition_or_measurement_approach":"IHC assessment at baseline for PD-L1, FAP, CD40 and evaluation of tertiary lymphoid structures (CD3/CD8/CD20 and CD68/SSP1/CXCL9)."}
• {"endpoint_text":"- On the serum: -\tAnti-drug antibodies (ADA) -\tMonitor the concentration of MP0317 drug (PK) in serum","definition_or_measurement_approach":"Serum assessments include ADA detection and pharmacokinetic monitoring of MP0317 concentration."}

France

Earliest CTIS Part Ii Submission Date

18-08-2025

Latest Decision Or Authorization Date

24-09-2025

Processing Time Days

37

Number Of Sites

11

Number Of Participants

75

Primary sponsor

Full Name

Centre Hospitalier Regional Universitaire

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France