Phase II Study on NIVolumab in Combination With FOLFOXIRI/Bevacizumab in First Line Chemotherapy of Advanced COloRectal Cancer RASm/BRAFm Patients

Gruppo Oncologico Italiano di Ricerca Clinica8 个研究点分布在 1 个国家目标入组 73 人开始时间: 2019年9月26日最近更新: 2025年3月13日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方
入组人数: 73
试验地点: 8
主要终点: ORR

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a multicentric single arm, open label trial. In this study patients candidated to a first line of chemotherapy for metastatic colorectal cancer will be treated with 8 cycles of folfoxiri plus bevacizumab plus nivolumab followed by a maintenance with bevacizumab plus nivolumab.

Patients who do not progress during chemotherapy phase will receive bevacizumab plus nivolumab as maintenance therapy.

Patients will be treated until disease progression, unacceptable toxicity or patient/physician decision.

详细描述

This is a prospective, open-label, multicentric phase II trial in which patients with metastatic colorectal cancer RASm/BRAFm patients will receive nivolumab in combination with FOLFOXIRI/Bevacizumab as first line chemotherapy.

Study screening will take place within 28 days prior to initiation of study treatment. At screening, every patient must have local RAS/BRAF known status. A centralized review of RAS/BRAF status will be performed during the study.

Eligible patients will be enrolled and begin treatment with FOLFOXIRI/bevacizumab plus nivolumab every 2 weeks for 8 cycles followed by maintenance with bevacizumab plus nivolumab every 2 weeks until disease progression, unacceptable toxicity or patient/physician decision. Bevacizumab will be administered intravenously at dose of 5 mg/kg every 2 weeks. Nivolumab will be administered intravenously at flat dose of 240 mg every 2 weeks.

Folfoxiri will be administered as 165 mg/m2 intravenous infusion of irinotecan for 60 min, followed by an 85 mg/m2 intravenous infusion of oxaliplatin given concurrently with leucovorin at a dose of 200 mg/m2 for 120 min, followed by a 3200 mg/m2 continuous infusion of fluorouracil for 48 h.

During the study treatment period, patients will be followed for safety based on AE assessments including vital signs, physical findings and clinical laboratory test results.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 75 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Written informed consent.
•Male or female of 18-75 years of age on day of signing informed consent.
•Histologically confirmed diagnosis of colorectal cancer RAS/BRAF mutated.
•Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
•Patients suitable for first line chemotherapy.
•Life expectancy > 3 months.
•At least one site of measurable disease per RECIST criteria.
•Performance status of 0-1 on the ECOG Performance Scale.
•Adequate organ function
•Availability at baseline of a representative formalin-fixed, paraffin-embedded (FFPE) diagnostic tumor specimen, as primary and/or metastatic tumor tissue block or as fifteen 5-micron unstained slides are allowed (the neoplastic cell content of each tumor sample will be assessed and in those cases with neoplastic cells <50% a macro-dissection of the specimen will be performed, if possible).
•If DPD status is known it must be wild type. No restriction are applied if DPD status in unknown.
•Women of childbearing potential must have a negative blood pregnancy test within 24 hr prior to the start of study drug. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive.
•Subjects and their partners must be willing to avoid pregnancy during the trial and until 5 months for WOCBP (Women of Childbearing Potential) and 7 months for male subjects with female partners of WOCBP after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator (barriers contraceptive measure or oral contraception).

排除标准

•Prior chemotherapy, excluded patient treated in neo/adjuvant setting at least 12 months before diagnosis of metastatic disease.
•Radiotherapy to any site within 4 weeks before the study.
•Serious, non-healing wound, ulcer, or bone fracture.
•Evidence of bleeding diathesis or coagulopathy.
•Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.
•Systemic corticosteroids within 2 weeks of the first dose of nivolumab.
•Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment.
•Additional malignancy in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
•Active and untreated brain (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are not using steroids for at least 7 days prior to trial treatment.
•Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger.
•Evidence of interstitial lung disease, active non-infectious pneumonitis, or a history of grade 3 or greater pneumonitis.
•Active infection requiring systemic therapy.
•History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
•Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection.
•Live vaccine within 30 days prior to the first dose of trial treatment.
•Chronic, daily treatment with high-dose aspirin (>325 mg/day).
•Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment.
•Any previous venous thromboembolism > NCI CTCAE Grade
•History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment.
•Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes.
•Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
•Presence of colic prosthesis or stent.
•History of any severe hypersensitivity reactions to any monoclonal antibody.
•Women of childbearing potential who are pregnant or breastfeeding.