A Phase 2, Open-label, Randomized, Multicenter, Platform Study of Novel Oncology Therapies in Combination With Adjuvant Chemotherapy in High-risk, Microsatellite-stable Colorectal Cancer (COLUMBIA-2)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- ctDNA clearance
研究概览
简要总结
Columbia 2 is a Phase 2 platform study to evaluate the safety and efficacy of standard of care (FOLFOX) alone and in combination with novel oncology therapies in adjuvant high-risk microsatellite-stable colorectal cancer
详细描述
Columbia 2 is a Phase 2, open-label, randomized, multicenter, platform study of novel oncology therapies in combination with adjuvant chemotherapy in patients with high-risk microsatellite-stable colorectal cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 101 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
- •Evidence of metastatic disease (including presence of tumor cells in ascites or peritoneal carcinomatosis resected "en bloc").
- •History of allogeneic organ transplantation.
- •Active or prior documented autoimmune disorders within the past 5 years as noted in the protocol.
- •Cardiac and vascular criteria:
- •History of venous thrombosis within the past 3 months prior to the scheduled first dose of study treatment.
- •Presence of acute coronary syndrome including myocardial infarction or unstable angina pectoris, other arterial thrombotic event including cerebrovascular accident or transient ischemic attack or stroke within the past 6 months prior to the scheduled first dose of study treatment.
- •New York Heart Association (NYHA) Class II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or uncontrolled hypertension.
- •History of hypertensive crisis/hypertensive encephalopathy within the past 6 months prior to the scheduled first dose of study treatment.
- •Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms
- •Uncontrolled intercurrent illness, see the protocol for details.
- •History of another primary malignancy except for: (a) Malignancy treated with curative intent and with no known active disease ≥ 5 years prior to the scheduled first dose of study treatment and of low potential risk for recurrence
- •History of active primary immunodeficiency.
- •Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.
- •Known allergy or hypersensitivity to any of the investigational product or noninvestigational product formulations.
- •Any condition that, in the opinion of the investigator, would prevent the initiation of 6 months adjuvant therapy within 8 weeks of surgery
- •Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment.
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the scheduled first dose of study treatment, or anticipation of the need for major surgical procedure during the course of the study.
- •Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment.
研究组 & 干预措施
Control Arm (mFOLFOX6)
Parts of mFOLFOX6 are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).
干预措施: Standard of Care - mFOLFOX6 (Drug)
Control Arm (mFOLFOX6)
Parts of mFOLFOX6 are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).
干预措施: E1 - mFOLFOX and durvalumab (Drug)
Control Arm (mFOLFOX6)
Parts of mFOLFOX6 are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).
干预措施: E2 - mFOLFOX6, durvalumab and oleclumab (Drug)
Control Arm (mFOLFOX6)
Parts of mFOLFOX6 are: Oxaliplatin 85 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Folinic acid (leucovorin) 400 mg/m2 IV infusion Q2W (Day 1 of every 14-day cycle), Fluorouracil (5-FU) 400 mg/m2 IV bolus on Day 1 then 2,400 mg/m2 over 46 to 48 hours IV infusion Q2W (Day 1-2 of every 14-day cycle).
干预措施: E3 - mFOLFOX6, durvalumab and monalizumab (Drug)
Durvalumab
Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle)
干预措施: E1 - mFOLFOX and durvalumab (Drug)
Durvalumab
Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle)
干预措施: E2 - mFOLFOX6, durvalumab and oleclumab (Drug)
Durvalumab
Durvalumab 1500 mg IV, Q4W (Day 1 of every other 14-day cycle)
干预措施: E3 - mFOLFOX6, durvalumab and monalizumab (Drug)
Oleclumab
Oleclumab 3,000 mg IV Q2W x5 then Q4W (Day 1 of every 14-day cycle through cycle 4 then Day 1 of every other 14-day cycle)
干预措施: E2 - mFOLFOX6, durvalumab and oleclumab (Drug)
Monalizumab
Monalizumab 750 mg IV, Q2W (Day 1 of every 14-day cycle)
干预措施: E3 - mFOLFOX6, durvalumab and monalizumab (Drug)
结局指标
主要结局
ctDNA clearance
时间窗: From the time of first dose to 6 months post treatment
ctDNA clearance is defined as the change from ctDNA positive status at baseline to ctDNA negative post baseline (6 months)
次要结局
- Incidence of adverse events(From time of first dose to 90 days post last dose)
- Disease free survival(From time of first dose till end of study (5 years))
- Disease free survival at 12 months(From time of first dose till end of study (5 years))
- overall survival(From time of first dose till end of study (5 years))
- Serum conenctration levels of novel agents in combination with mFOLFOX6(From Day 1 up to 90 days post last dose)
- Number of subjects with detectable anti-drug antibody (ADA) to novel agents in combination with mFOLFOX6(From Day 1 up to 90 days post last dose)