Testing Mitazalimab in Combination With Standard Chemotherapy in Immunotherapy Resistant Advanced Biliary Tract Cancers

Официальное название

Countering Immunotherapy Resistance With Novel Combinations in Advanced Biliary Tract Cancers

Обзор

The goal of this clinical trial is to etablish whether adding Mitazalimab to standard chemotherapy is more effective than standard chemotherapy alone in people with advanced bile duct cancer. It will also learn about the safety of Mitazalimab. The main questions it aims to answer are: * Does the addition of Mitazalimab enhance efficacy? * What medical problems do participants have when taking Mitazalimab + mFOLFOX? Participants will: * Take drug mFOLFOX every two weeks until disease progression or mFOLFOX every two weeks plus mitazalimab in addition to mFOLFOX, with a first injection 7 days before the first mFOLFOX chemotherapy and then 3 days after the start of each mFOLFOX cycle. * Visit the clinic once every 2 weeks for checkups and tests * Have a radiological assessment every 8 weeks during treatment. After stopping treatment, participants will be monitored at the hospital every 8 weeks if no progression is observed, or every 12 weeks after disease progression.

Подробное описание

Multicenter, open-label, randomized phase II/III trial evaluating the efficacity of mitazalimab in combination with mFOLFOX compared to mFOLFOX alone in participant advanced BTC

Вмешательства

• Препарат mFOLFOX regimen
  oxaliplatin 85 mg/m² intravenous infusion (IV), folinic acid 400 mg/m² IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m² as a 46-hours continuous IV infusion: * every two week (14-day cycles) until disease progression on control arm * at D8 the first cycle and at D1 for subsequent cycles (14-day cycles) until disease progression on experimental arm
• Препарат Mitazalimab
  The first cycle of treatment (21-day cycle): Mitazalimab 900 µg/kg by intravenous infusion (IV) at D1 and D10 Subsequent cycles (14-day cycles): Mitazalimab 900 µg/kg by intravenous infusion (IV) at D3 of each cycle until disease progression

Первичные конечные точки

• 6 months overall survival rate of participants [Срок оценки: From randomisation to 6 months after randomisation]

Вторичные конечные точки (9)

• Safety of the treatments [Срок оценки: From inclusion to completion of the study, up to 64 months]
• Objective response rate of participants (ORR) [Срок оценки: Time from randomisation to disease progression, up to 64 months]
• Disease control rate (DCR) [Срок оценки: Time from randomisation to disease progression, up to 64 months]
• Progression-free survival (PFS) [Срок оценки: Time from randomisation to disease progression or death, up to 64 months]
• Duration of overall response (DOR) [Срок оценки: Time from randomisation to disease progression or death, up to 64 months]
• Overall survival (OS) [Срок оценки: From randomisation to death from any cause, up to 64 months]
• Quality of life questionnaire - Core Function 17 (QLQ-F17) [Срок оценки: Baseline and every 2 months during the first year after randomisation]
• Quality of life Questionnaire - Biliary tract cancer module (QLQ-BIL21) [Срок оценки: Baseline and every 2 months during the first year after randomisation]
• The Developed 5-level version of EQ-5D (EQ-5D-5L) questionnaire [Срок оценки: At Baseline and every 2 months during the first year after randomisation]

Критерии участия

Критерии включения

• Age ≥18 years
• Histologically-proven intrahepatic cholangiocarcinoma, extrahepatic (perihilar/distal) cholangiocarcinoma, or gallbladder carcinoma (ampullary carcinoma excluded)
• Measurable tumor according to RECIST v1.1 classification
• Non-resectable or metastatic disease or recurrent after surgery (if recurrence more than 6 months after adjuvant treatment stop)
• Participants having received a standard first-line treatment (CISGEM + durvalumab or pembrolizumab) and eligible for second- or third-line treatment with FOLFOX. Participant could have received a previous targeted therapy in case of targetable alteration, but only one line of chemotherapy is permitted.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate bone marrow reserve, normal renal and liver functions:

• Neutrophil count ≥ 1500/mm³
• Platelet count ≥ 150 000/mm³
• Hemoglobin ≥ 10 g/dl
• Estimated glomerular filtration rate (eGFR) value ≥50 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
• Total bilirubin < 1.5 x ULN (after biliary stent placement in case of biliary obstruction)
• No dihydropyrimidine dehydrogenase deficiency, as assessed by pre-treatment uracil blood level ≤ 16 ng/mL
• Women of childbearing potential must have a negative serum or urine pregnancy test done within 7 days before randomization.
• Participants must agree to use adequate contraception methods for the duration of study treatment and for within 15 months for women and 12 months for men after completing treatment.
• Participants must be affiliated to a Social Security System (or equivalent).
• Participant must have signed a written informed consent prior to any trial specific procedures. When the participant is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the participant's consent.
• Participants must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.
• Have archival tumor tissue sample that has been identified and confirmed as available
• Participant having consented for a new tumor biopsy at inclusion for ancillary studies (participants with non-contributory new biopsy may still be included in the study).

Критерии исключения

• Participants having received previous treatment with fluoropyrimidine, oxaliplatin or CD40 agonist, except for capecitabine given as adjuvant treatment (if last administered > 6 months).
• Concurrent malignancy (other than BTC), with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 3 years or more and are deemed at negligible risk for recurrence, are eligible for the trial
• Known CNS metastases or carcinomatous meningitis
• History of chronic diarrhea, inflammatory disease of the colon or rectum, or unresolved partial or complete intestinal obstruction
• History of myocardial infarction within 12 months of the first administration of mitazalimab, uncontrolled angina pectoris, unstable cardiac arrhythmias, or congestive heart failure of New York Heart Association class II or greater
• QTc >450 msec
• Known history of HIV, hepatitis B or active hepatitis C infection
• Toxicities from first-line treatment not resolved to Grade ≤ 1 (according to NCI-CTCAE v6.0) before randomization with the exception of alopecia
• Contraindication to mitazalimab or to FOLFOX regimen, or their excipients
• Prior toxicities of grade ≥ 3 with durvalumab or pembrolizumab (except from vitiligo, alopecia, hypothyroidism, adrenal insufficiency and diabetes) or other immune-related toxicities that led to definitive discontinuation
• Has received attenuated vaccine within 28 days before the first dose of study treatment
• Any condition which in the Investigator's opinion makes it undesirable for the participant to participate in the trial or which would jeopardize compliance with the protocol (including uncontrolled comorbidities, active infections or untreated central nervous system metastases)
• Participation in another therapeutic trial within the 30 days prior to randomization
• Pregnant women or women who are breast-feeding
• Participant unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
• Individual deprived of liberty or placed under protective custody or guardianship.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 22 центра

• Institut de cancérologie de l'Ouest - Site Paul Papin — Angers
• CHU de Bordeaux - Hopital Haut Leveque — Bordeaux
• CHU Brest — Brest
• Centre François Baclesse — Caen
• CHU Estaing — Clermont-Ferrand
• CHU de Dijon — Dijon
• CHU Grenoble Alpes — Grenoble
• CHU Lille — Lille
• … и ещё 14 центров

Идентификаторы

NCT: NCT07437287 · UC-GIG-2519

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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