Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (Amended Protocol of: Nivolumab, Ipilimumab and COX2-inhibition in Early Stage Colon Cancer: an Unbiased Approach for Signals of Sensitivity: The NICHE TRIAL)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 353
- 试验地点
- 6
- 主要终点
- Incidence of adverse events during the treatment and follow-up (safety)
研究概览
简要总结
In this exploratory study, patients with stage 1-3 adenocarcinoma of the colon with no signs of distant metastases will be treated with short-term immunotherapy + novel IO combinations (i.e. anti-IL 8, COX2-inhibitors, anti-LAG3). This treatment will be given during the window period until surgical resection of the tumor. The duration of treatment will be in between approximately 6 and 12 weeks.
详细描述
In this multi-center, open-label, exploratory study, the investigators will enroll 60 patients within two years, including 30 patients with MSS tumors and 30 patients with MSI tumors. Patients with MSS tumors will be randomized to either group 1 or 2. Patients with MSI tumors will all be allocated to group 1.
Patients in group 1 will be treated with a single dose of ipilimumab 1mg/kg on day 1 and two cycles of nivolumab 3mg/kg on day 1 and 15, respectively.
Patients in group 2 will be treated with a single dose of ipilimumab 1mg/kg on day 1, two cycles of nivolumab 3mg/kg one day 1 and 15 and celecoxib daily until the day before surgery.
The study was amended in May 2020 to enroll an additional 70 patients in the MSI cohort after the first 30 patients, making a total of 100 patients with MSI tumors. A formal sample size calculation and primary endpoint of 3-year disease-free-survival (DFS) for this group was added.
The study was amended in July 2021 to add a new cohort, cohort 4, for patients with pMMR/MSS tumors. Once accrual of 30 evaluable patients in group 2 was completed, a new cohort opened in which patients will receive nivolumab plus anti-IL8 (BMS-986253).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（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
- 未提供
研究组 & 干预措施
group 1 - closed
drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV)
干预措施: Nivolumab (Drug)
group 1 - closed
drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV)
干预措施: Ipilimumab (Drug)
group 2 - closed
drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV) drug: celecoxib 200 mg daily (oral)
干预措施: Nivolumab (Drug)
group 2 - closed
drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV) drug: celecoxib 200 mg daily (oral)
干预措施: Ipilimumab (Drug)
group 2 - closed
drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV) drug: celecoxib 200 mg daily (oral)
干预措施: Celecoxib 200mg (Drug)
Anti-IL8 cohort 4 (pMMR/MSS tumors) - closed
drug: nivolumab 3 mg/kg day 1 and day 15 (IV) drug: BMS-986253 (anti-IL8) 2400mg on day 1 and day 15 (IV)
干预措施: Nivolumab (Drug)
Anti-IL8 cohort 4 (pMMR/MSS tumors) - closed
drug: nivolumab 3 mg/kg day 1 and day 15 (IV) drug: BMS-986253 (anti-IL8) 2400mg on day 1 and day 15 (IV)
干预措施: BMS-986253 (Drug)
Relatlimab cohort 5 (pMMR/MSS tumors)
drug: nivolumab 240mg IV on day 1 and day 15 drug: relatlimab 240mg IV on day 1 and day 15
干预措施: Nivolumab (Drug)
Relatlimab cohort 5 (pMMR/MSS tumors)
drug: nivolumab 240mg IV on day 1 and day 15 drug: relatlimab 240mg IV on day 1 and day 15
干预措施: BMS-986016 (Drug)
Relatlimab cohort 6 (dMMR/MSI tumors) - closed
drug: nivolumab 480mg IV on day 1 and day 29 drug: relatlimab 480mg IV on day 1 and day 29
干预措施: Nivolumab (Drug)
Relatlimab cohort 6 (dMMR/MSI tumors) - closed
drug: nivolumab 480mg IV on day 1 and day 29 drug: relatlimab 480mg IV on day 1 and day 29
干预措施: BMS-986016 (Drug)
Cohort 7 - dMMR - 3 cycles neoadjuvant nivolumab + relatlimab
Patients with dMMR tumors will be treated with 3 cycles of neoadjuvant nivolumab (480mg) + relatlimab (160mg) on day 1, day 29 and day 57 followed by surgery within 12 weeks and not earlier than 10 weeks from enrollment
干预措施: Nivolumab (Drug)
Cohort 7 - dMMR - 3 cycles neoadjuvant nivolumab + relatlimab
Patients with dMMR tumors will be treated with 3 cycles of neoadjuvant nivolumab (480mg) + relatlimab (160mg) on day 1, day 29 and day 57 followed by surgery within 12 weeks and not earlier than 10 weeks from enrollment
干预措施: BMS-986016 (Drug)
Cohort 8 - dMMR - 3 cycles neoadjuvant nivolumab
Patients with dMMR tumors will be treated with 3 cycles of neoadjuvant nivolumab (480mg) on day 1, day 29 and day 57 followed by surgery within 12 weeks and not earlier than 10 weeks from enrollment.
干预措施: Nivolumab (Drug)
结局指标
主要结局
Incidence of adverse events during the treatment and follow-up (safety)
时间窗: until 100 days after last patient last study drug treatment
Adverse events will be assessed (according to CTCAE v4.0) during treatment and follow-up.
Disease free survival
时间窗: until 5 years after diagnosis
To assess efficacy of neoadjuvant ipilimumab plus nivolumab in terms of disease-free survival
Major Pathological Response
时间窗: From date of randomization until the date of first documented progression, assessed up to 63 months
To assess efficacy of neoadjuvant nivolumab monotherapy and neoadjuvant nivolumab plus relatlimab in terms of major pathologic response
次要结局
- Relapse free survival(3-5 years after last patient inclusion.)
- Immune activating capacity of short-term pre-operative immunotherapy(within 2 years after study completion)