Modified Short-Course Radiation Combined With CAPOX and Tislelizumab for MSS Locally Advanced of Middle and Low Rectal Cancer (mRCAT): An Open-label, Single-arm, Prospective Multicenter Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Pathological complete response (pCR) rate
研究概览
简要总结
This is an open-label, prospective, multicenter phase II clinical trial to evaluate modified short-course radiation (Radiation targeting the tumor bed without irradiating surrounding tumor-draining lymph nodes) combined with CAPOX and PD-1 Inhibitor (Tislelizumab) for patients with MSS middle and low rectal cancer. A total of 32 patients will be enrolled in this trial. The primary endpoint is the rate of pathological complete response (pCR). The organ preservation rate, tumor regression grade, long-term prognosis, 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/cT3-4aN0/+M0, the lymph nodes are limited to the mesorectum, the circumferential resection margin is negative.
- •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 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, followed by total mesorectal excision surgery.
干预措施: Modified short-course radiotherapy (Radiation)
Treatment Arm
Participants will receive 5*5Gy 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, followed by total mesorectal excision surgery.
干预措施: PD-1 antibody (Drug)
Treatment Arm
Participants will receive 5*5Gy 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, followed by total mesorectal excision surgery.
干预措施: Capecitabine (Drug)
Treatment Arm
Participants will receive 5*5Gy 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, followed by total mesorectal excision surgery.
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 surgery
The status of pCR will be evaluated after the TME surgery.
次要结局
- Tumor regression grade(within 10 days after surgery)
- Local recurrence rate(LRR)(3 years after sugery)
- Disease free survival(DFS)(3 years after surgery)
- Overall survival(OS)(3 years after surgery)
- Adverse effects rate(From date of initiation of treatment until the date of death from any cause, assessed up to 5 years)
- Rectal specific quality of life assessment via QLQ-CR29(Baseline and months 3, 6, 12, 24, 36, 60 after the surgery)
- Quality of life assessment via QLQ-C30(Baseline and months 3, 6, 12, 24, 36, 60 after the surgery)
- Validation of the Wexner score(Months 3, 6, 12, 24, 36, 60 after the surgery)