A Phase II Randomized Controlled Trial of Neoadjuvant Immunotherapy With or Without Radiotherapy in Locally Advanced Microsatellite Instability-High/Mismatch Repair-Deficient Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- Complete regression (CR) rate
研究概览
简要总结
This phase II clinical trial evaluates the efficacy and safety of three neoadjuvant regimens in patients with locally advanced microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer (CRC): 1) Regimen A: Dual immune checkpoint blockade with nivolumab plus ipilimumab. 2) Regimen B: Nivolumab plus radiotherapy. 3) Regimen C: Nivolumab monotherapy. The primary objectives are to determine whether: 1) Dual immune checkpoint blockade (Regimen A) is superior to nivolumab monotherapy (Regimen C); and 2) Immunotherapy plus radiotherapy (Regimen B) is superior to nivolumab monotherapy (Regimen C). Methods: Participants will be randomized in a 1:1:1 ratio to one of the three arms. For patients with resectable tumors, surgical resection will be performed. In patients with low rectal cancer and poor prospects for sphincter preservation, a watch-and-wait (WW) strategy is an option if a clinical complete response (CR) is achieved following neoadjuvant therapy.
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
- •Histopathologically confirmed primary colorectal adenocarcinoma.
- •Radiographic assessment showed a stage II-III based on AJCC Stage 8th ed.
- •At least 18 years old.
- •MSI-H or dMMR.
- •The Eastern Cooperative Oncology Group performance status (ECOG PS) score is 0 or
- •Physical state or organ function can tolerate the planned treatment of the study protocol.
- •Agreed to sign written informed consent before recruitment.
排除标准
- •Previously received any antitumor therapy for the disease under study, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
- •Pregnancy or breastfeeding women.
- •History of other malignancies within 5 years.
- •Serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.
- •Immunodeficiency disease or long-term using of immunosuppressive agents.
- •Allergic to any component of the therapy.
- •Any other condition or disease that is not suitable to take the therapy included in the protocol.
- •Concurrent participation in another clinical study, unless participating in an observational (non-interventional) clinical study or in the survival follow-up phase of an interventional study.
- •Received any investigational drug or device treatment within 4 weeks prior to initial administration of the investigational drug.
研究组 & 干预措施
anti-PD-1 plus radiotherapy
Arm B: Radiotherapy (5 Gy per fraction, total 4 fractions, delivered every 3 weeks) to the primary lesion plus nivolumab 240 mg every 2 weeks (6 doses).
干预措施: Watch & wait (Other)
anti-PD-1 monotherapy
Arm C: Nivolumab 240 mg every 2 weeks (6 doses).
干预措施: Nivolumab (Drug)
anti-PD-1 monotherapy
Arm C: Nivolumab 240 mg every 2 weeks (6 doses).
干预措施: Radical surgery (Procedure)
anti-PD-1 plus anti-CTLA-4
Arm A: Nivolumab 240 mg every 2 weeks (6 doses) plus ipilimumab 1 mg/kg every 3 weeks (4 doses).
干预措施: Nivolumab (Drug)
anti-PD-1 plus anti-CTLA-4
Arm A: Nivolumab 240 mg every 2 weeks (6 doses) plus ipilimumab 1 mg/kg every 3 weeks (4 doses).
干预措施: Ipilimumab (1mg/kg) (Drug)
anti-PD-1 plus anti-CTLA-4
Arm A: Nivolumab 240 mg every 2 weeks (6 doses) plus ipilimumab 1 mg/kg every 3 weeks (4 doses).
干预措施: Radical surgery (Procedure)
anti-PD-1 plus anti-CTLA-4
Arm A: Nivolumab 240 mg every 2 weeks (6 doses) plus ipilimumab 1 mg/kg every 3 weeks (4 doses).
干预措施: Watch & wait (Other)
anti-PD-1 plus radiotherapy
Arm B: Radiotherapy (5 Gy per fraction, total 4 fractions, delivered every 3 weeks) to the primary lesion plus nivolumab 240 mg every 2 weeks (6 doses).
干预措施: Nivolumab (Drug)
anti-PD-1 plus radiotherapy
Arm B: Radiotherapy (5 Gy per fraction, total 4 fractions, delivered every 3 weeks) to the primary lesion plus nivolumab 240 mg every 2 weeks (6 doses).
干预措施: PULSAR (Radiation)
anti-PD-1 plus radiotherapy
Arm B: Radiotherapy (5 Gy per fraction, total 4 fractions, delivered every 3 weeks) to the primary lesion plus nivolumab 240 mg every 2 weeks (6 doses).
干预措施: Radical surgery (Procedure)
anti-PD-1 monotherapy
Arm C: Nivolumab 240 mg every 2 weeks (6 doses).
干预措施: Watch & wait (Other)
结局指标
主要结局
Complete regression (CR) rate
时间窗: 1 month after surgery or the completion of neoadjuvant therapy
Proportion of patients achieving either clinical CR (and undergoing WW) or pathological CR (confirmed by pathology) among all evaluable patients.
次要结局
- Surgical mortality(During or one month after surgery)
- R0 resection rate(1 month after surgery)
- Objective response rate (ORR)(6 months after the enrollment of the last subject)
- Event-free survival (EFS)(36 months after the enrollment of the last subject)
- Overall survival (OS)(36 months after the enrollment of the last subject)
- Toxicities(From the time of enrollment, assessed up to 28 days after the last dose of study therapy)
- Surgical morbidity(During or one month after surgery)
研究者
Zhen Zhang
Professor, Chief Physician, Department of Radiation Oncology, Fudan University Shanghai Cancer Center
Fudan University