Node-sparing Modified Short-Course Radiation Combined With CAPOX and Tislelizumab for MSS Locally Advanced of Middle and Low Rectal Cancer : An Randomized, Prospective, Multicenter, Open-label, Phase III Clinical Trial (mRCAT-III)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 170
- 试验地点
- 1
- 主要终点
- pathological complete response (pCR) rate
研究概览
简要总结
This is a randomized, prospective, multicenter, open-label, Phase III clinical trial to evaluate node-sparing modified short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with CAPOX and PD-1 Inhibitor (Tislelizumab) compared with standard short-course radiation combined with CAPOX for patients with MSS middle and low rectal cancer. A total of 170 patients will be enrolled in this trial. The primary endpoint is the rate of pathological complete response (pCR). The EFS rate, ORR, organ preservation rate, long-term prognosis, and adverse effects will also be analyzed.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy.
- •Male or Female aged 18-
- •Patients diagnosed with low rectal cancer within 10 cm from the lower edge of the tumor to the anal verge by pelvic MRI and anorectoscopy, the clinical stage is cT3-4bN0/+M0, and the lymph nodes are limited to the mesorectum.
- •Histologically confirmed rectal adenocarcinoma; Genetic testing suggests MSI-L or MSS, or tumor biopsy immunohistochemistry reveals pMMR, that is, MSH1, MSH2, MSH6, and PMS2 are all positive.
- •Eastern Cooperative Oncology Group (ECOG) score 0-
- •No previous treatment (including anti-tumor therapy, immunotherapy or pelvic radiation).
- •Laboratory tests indicating no contraindications to radiotherapy, chemotherapy and immunotherapy.
- •Informed consent form signed.
排除标准
- •Patients with a previous history of malignant tumors besides rectal cancer.
- •Patients with distant metastases before enrollment.
- •Patients with positive internal or external iliac lymph nodes are assessed by MRI or CT.
- •Patients with obstruction, perforation, or bleeding that require emergency surgery.
- •Patients with severe concomitant diseases and estimated survival time ≤ 5 years.
- •Allergic to any component of the therapy.
- •Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy.
- •Patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening.
- •Factors leading to study termination, such as alcoholism, drug abuse, other serious illnesses (including psychiatric disorders) requiring combination therapy, and patients with severe laboratory abnormalities.
- •Patients with congenital or acquired immune deficiency (such as HIV infection).
- •Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, pregnant or lactating women, illiterate, etc.
- •Other conditions that investigators consider not suitable for this study.
研究组 & 干预措施
Treatment Arm
Participants will receive 5*5Gy node-sparing modified short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.
干预措施: node-sparing modified short-course radiotherapy (Radiation)
Treatment Arm
Participants will receive 5*5Gy node-sparing modified short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.
干预措施: PD-1 antibody (Drug)
Standard Arm
Participants will receive 5*5Gy standard short-course radiation (radiation targeting the tumor bed and surrounding tumor-draining lymph nodes) concurrently with CAPOX regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14. CAPOX repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.
干预措施: standard short-course radiotherapy (Radiation)
Exploration Arm
Participants will receive 5*5Gy standard short-course radiation (radiation targeting the tumor bed and surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.
干预措施: PD-1 antibody (Drug)
Exploration Arm
Participants will receive 5*5Gy standard short-course radiation (radiation targeting the tumor bed and surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.
干预措施: standard short-course radiotherapy (Radiation)
Treatment Arm
Participants will receive 5*5Gy node-sparing modified short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.
干预措施: Capecitabine (Drug)
Treatment Arm
Participants will receive 5*5Gy node-sparing modified short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.
干预措施: Oxaliplatin (Drug)
Standard Arm
Participants will receive 5*5Gy standard short-course radiation (radiation targeting the tumor bed and surrounding tumor-draining lymph nodes) concurrently with CAPOX regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14. CAPOX repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.
干预措施: Capecitabine (Drug)
Standard Arm
Participants will receive 5*5Gy standard short-course radiation (radiation targeting the tumor bed and surrounding tumor-draining lymph nodes) concurrently with CAPOX regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14. CAPOX repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.
干预措施: Oxaliplatin (Drug)
Exploration Arm
Participants will receive 5*5Gy standard short-course radiation (radiation targeting the tumor bed and surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.
干预措施: Capecitabine (Drug)
Exploration Arm
Participants will receive 5*5Gy standard short-course radiation (radiation targeting the tumor bed and surrounding tumor-draining lymph nodes) concurrently with CAPOX and tislelizumab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and tislelizumab, 200mg intravenous infusion d1 of each cycle. CAPOX and tislelizumab repeat every 3 weeks for 4 cycles. After treatment, digital rectal examination, pelvic MRI, endoscopy, and biopsy will be performed to evaluate the tumor regression grade. Patients will receive TME surgery after the chemo-immunotherapy, pCR rate and TRG grade will be evaluated.
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
pathological complete response (pCR) rate
时间窗: within 10 days after completion of surgery
Pathological complete response (pCR) rate
次要结局
- Rectal specific quality of life assessment via QLQ-CR29 Rectal specific quality of life assessment via QLQ-CR29 Rectal specific quality of life assessment via QLQ-CR29(Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery)
- Quality of life assessment via QLQ-C30(Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery)
- Validation of the Wexner score(Baseline and months 3, 6, 12, 24, 36, 60 after the chemotherapy or surgery)
- organ preservation rate(within 10 days after completion of chemotherapy)
- event free survival (EFS)(3 years after randomization)
- overall response rate (ORR)(within 10 days after completion of chemotherapy)
- Disease free survival(DFS)(3 years after chemotherapy or surgery)
- Overall survival(OS）(3 years after chemotherapy or surgery)
- Adverse effects rate(From date of initiation of treatment until the date of death from any cause, assessed up to 5 years)
研究者
Zhangfa Song
Vice president
Sir Run Run Shaw Hospital