A Phase II Study Evaluating an Organ Preservation Strategy Using Immune Checkpoint Blockade for Participants With Primary Colorectal or Gastroesophageal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Clinical complete response (CR) or near-complete response (nCR)
研究概览
简要总结
Background:
People with colorectal cancer (CRC) or gastroesophageal cancer (GEC) must often have major surgery to remove tumors from the esophagus, stomach, colon, or rectum. These surgeries can have adverse effects on their quality of life. Researchers want to know if one or two approved drugs (nivolumab with or without ipilimumab) can help people with CRC or GEC delay or avoid surgery.
Objective:
To test 1 or 2 drugs in people with CRC or GEC.
Eligibility:
People aged 18 years and older with CRC or GEC. People with GEC must also have changes in a particular gene.
Design:
Participants will visit the clinic about 15 times over the first 2 years. Each visit will last 4 to 8 hours.
Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans. Small samples of tissue will be collected from their upper or lower digestive tract where the tumor is located.
Both ipilimumab and nivolumab are administered through a tube attached to a needle inserted into a vein in the arm. Some participants will receive both drugs. Some will receive only nivolumab. Treatment will be given once every 3 weeks for up to 8 cycles up to (24 weeks).
Participants will be evaluated every 6 weeks. Those who are responding well will continue with the drug treatments. If their disease progresses, they will go to surgery.
After treatment ends, participants will have follow-up visits every 6 months for up to 5 years....
详细描述
Background:
- Immune checkpoint blockade (ICB) using antibodies against programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte associated protein 4 (CTLA-4) can induce major pathologic responses (MPR) in approximately 23% of mismatch repair (MMR) proficient colorectal cancers, 90% of MMR deficient colorectal cancers and 74% of MMR deficient gastroesophageal cancers.
- MPR after ICB, defined as >90% treatment response, is associated with exceptional local and distant disease-free survival (DFS). This has been observed in participants with advanced melanoma, MMR deficient colorectal cancer and MMR deficient gastroesophageal cancer.
- We hypothesize that it is safe to forego surgical resection in participants who have had an MPR to ICB. To test this hypothesis, we designed an organ preservation strategy for participants with colorectal cancer and gastroesophageal cancer using induction ICB and close interval surveillance.
Objectives:
Primary objective:
--Determine the rate of clinical complete response (CR) or near-complete response (nCR) after induction ICB in participants with MMR proficient colorectal cancer (Cohort 1), MMR deficient colorectal cancer (Cohort 2) and MMR deficient gastroesophageal cancer (Cohort 3).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 120 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
- 未提供
研究组 & 干预措施
1: nivolumab and ipilimumab
Nivolumab (3 mg/kg) every 3 weeks for up to an initial 4 cycles (an additional 4 cycles may be given depending on response, for a total of 8 cycles); low-dose ipilimumab at 1 mg/kg every other cycle (every 6 weeks) for up to an initial 2 doses (an additional 2 doses may be given depending on response, for a maximum of 4 doses).
干预措施: nivolumab (Drug)
1: nivolumab and ipilimumab
Nivolumab (3 mg/kg) every 3 weeks for up to an initial 4 cycles (an additional 4 cycles may be given depending on response, for a total of 8 cycles); low-dose ipilimumab at 1 mg/kg every other cycle (every 6 weeks) for up to an initial 2 doses (an additional 2 doses may be given depending on response, for a maximum of 4 doses).
干预措施: ipilimumab (Drug)
2: nivolumab
Nivolumab (3 mg/kg) every 3 weeks for up to an initial 4 cycles (an additional 4 cycles may be given depending on response, for a total of 8 cycles).
干预措施: nivolumab (Drug)
结局指标
主要结局
Clinical complete response (CR) or near-complete response (nCR)
时间窗: 6, 12 18 and 24 weeks
Assessed endoscopically with concordant radiographic findings clinical CR/nCR in each cohort will be reported along with 80% and 95% two-sided confidence intervals.
次要结局
- Delay in surgery(until 30 days after documented progressive disease)
- Disease free survival (DFS)(6, 12 18 and 24 weeks then every 4 months for 2 years then every 6 months for years 3-5)
- Resection-free survival (RFS)(6, 12 18 and 24 weeks then every 4 months for 2 years then every 6 months for years 3-5)
- Locoregional failure(6, 12 18 and 24 weeks then every 4 months for 2 years then every 6 months for years 3-5)
- Safety(until 30 days after the last dose of study drugs)