Total Neoadjuvant CAPOX And PD-1 Inhibitor（Sintilimab） Combined With Node-sparing Short-course Radiotherapy For MSS Locally Advanced Of Middle And Low Rectal Cancer(CASINOs): An Open Label, Single-arm, Prospective Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Complete response
研究概览
简要总结
phase II clinical trial to evaluate node-sparing short-course radiation combined with total neoadjuvant CAPOX and Sintilimab for MSS locally advanced rectal cancers.
详细描述
This is an open-label, prospective, single-center phase II clinical trial to evaluate node-sparing short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with total neoadjuvant CAPOX and PD-1 Inhibitor (Sintilimab) for patients with MSS locally advanced of middle and low rectal cancer. A total of 37 patients will be enrolled in this trial. The primary endpoint is the complete response(CR) rate, which includes cCR and pCR. The organ preservation rate, tumor regression grade, 3-year DFS, 3-year OS, and adverse effects will also be analyzed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 cT2N+M0/cT3-4N0/+M0, 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) 0-
- •No previous treatment(including anti-tumor therapy、immunotherapy or pelvic radiation).
- •Adequate hematologic, hepatic, renal, thyroid and cardiac function: white blood cells ≥3500/mm3, neutrophils ≥1800/mm3, platelets ≥100,000/mm3, hemoglobin ≥100 g/L; activated partial thromboplastin time, prothrombin time and international normalized ratio ≤1.5 × ULN; aspartate aminotransferase and alanine aminotransferase ≤3.0 × upper limit of normal (ULN), bilirubin ≤1.25 × ULN, serum albumin ≥28 g/L. creatinine clearance ≥50 mL/mi, creatinine ≤1.5 × ULN;
- •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 with poorly differentiated adenocarcinoma, signet ring cell carcinoma, or mucinous adenocarcinoma.
- •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 short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 6 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery.
Interventions:
- Radiation: node-sparing short-course radiation
- Drug: PD-1 antibody (Sintilimab)
- Drug: Capecitabine
- Drug: Oxaliplatin
干预措施: node-sparing short-course radiotherapy (Radiation)
Treatment Arm
Participants will receive 5*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 6 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery.
Interventions:
- Radiation: node-sparing short-course radiation
- Drug: PD-1 antibody (Sintilimab)
- Drug: Capecitabine
- Drug: Oxaliplatin
干预措施: Oxaliplatin (Drug)
Treatment Arm
Participants will receive 5*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 6 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery.
Interventions:
- Radiation: node-sparing short-course radiation
- Drug: PD-1 antibody (Sintilimab)
- Drug: Capecitabine
- Drug: Oxaliplatin
干预措施: TME surgery (Procedure)
Treatment Arm
Participants will receive 5*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 6 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery.
Interventions:
- Radiation: node-sparing short-course radiation
- Drug: PD-1 antibody (Sintilimab)
- Drug: Capecitabine
- Drug: Oxaliplatin
干预措施: watch and wait (Procedure)
Treatment Arm
Participants will receive 5*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 6 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery.
Interventions:
- Radiation: node-sparing short-course radiation
- Drug: PD-1 antibody (Sintilimab)
- Drug: Capecitabine
- Drug: Oxaliplatin
干预措施: Sintilimab (Drug)
Treatment Arm
Participants will receive 5*5Gy node-sparing short-course radiation (radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) concurrently with total neoadjuvant CAPOX and sintilimab regimens: Oxaliplatin, 130mg/m2, intravenous infusion,d1 of each cycle; Capecitabine, 1000mg/m2, PO, BID, d1-14 and sintilimab, 200mg intravenous infusion d1 of each cycle. CAPOX and sintilimab are repeated every 3 weeks for 6 cycles. Patients with cCR will be managed with a WW strategy, and patients who did not achieve cCR will receive TME surgery.
Interventions:
- Radiation: node-sparing short-course radiation
- Drug: PD-1 antibody (Sintilimab)
- Drug: Capecitabine
- Drug: Oxaliplatin
干预措施: Capecitabine (Drug)
结局指标
主要结局
Complete response
时间窗: within 10 days after TNT therapy or surgery
Pathological complete response (pCR) ：absence of residual tumour on resected specimen. Clinical complete response（cCR）: no residual tumour visible on imaging or colonoscopy and biopsy.
次要结局
- Overall survival(OS)(3 years after enrollment)
- Rectal specific quality of life assessment via QLQ-CR29(Baseline and months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery)
- Tumor regression grade(within 10 days after surgery)
- Local recurrence rate(LRR)(3 years after sugery)
- Disease free survival(DFS)(3 years after treatment)
- Adverse effects rate(From date of initiation of treatment until the date of death from any cause, assessed up to 5 years)
- Quality of life assessment via QLQ-C30(Baseline and months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery)
- Validation of the Wexner score(Months 3, 6, 12, 24, 36, 60 after the TNT treatment or surgery)
研究者
Cheng Cai
Clinical Professor
Jinhua Central Hospital