Neoadjuvant Moderately Hypofractionated Radiotherapy Combined With Chemotherapy and Immunotherapy for High-risk pMMR/MSS Locally Advanced Rectal Cancer: A Prospective, Multi-center Randomized Control Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 165
- 试验地点
- 1
- 主要终点
- Complete Remission (CR) Rate
研究概览
简要总结
This study aims to observe and evaluate the efficacy and safety of moderately hypofractionated radiotherapy combined with chemotherapy and immunotherapy, compared with conventional neoadjuvant chemoradiotherapy, in patients with high-risk locally advanced colorectal cancer.
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
- •Age ≥ 18 years and ≤ 75 years.
- •Histologically confirmed colorectal adenocarcinoma with the lower margin of the lesion ≤ 10 cm from the anal verge as assessed by MRI, and immunohistochemistry confirming pMMR, or genetic testing demonstrating MSI-L or MSS.
- •Presence of at least one of the following high-risk factors as assessed by pelvic MRI: cT4a/b; N2; extramural vascular invasion (EMVI+); mesorectal fascia involvement (MRF+); enlarged lateral lymph node (longest diameter > 7 mm).
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1
- •No prior surgery, radiotherapy, chemotherapy, or targeted therapy.
- •Able to tolerate radiotherapy, chemotherapy, and immunotherapy: ECOG performance status score 0-
- •Laboratory results: white blood cell count ≥ 4.0 × 10⁹/L, platelet count ≥ 100 × 10⁹/L, hemoglobin ≥ 80 g/L, ALT < 2 × ULN, total bilirubin < 35 μmol/L, serum creatinine < 1.5 × ULN or creatinine clearance ≥ 50 mL/min, thyroid-stimulating hormone within normal range (patients with stable thyroid function after hormone replacement therapy may be enrolled).
- •Willing to participate and able to provide written informed consent.
排除标准
- •Presence of distant metastasis.
- •Patients with stage I or II rectal cancer who do not require preoperative neoadjuvant therapy.
- •Severe diseases involving the heart, lung, brain, kidney, gastrointestinal tract, or other systemic conditions.
- •Untreated chronic hepatitis B or HBV carriers with HBV DNA > 500 IU/mL, or patients positive for HCV RNA. Patients with inactive hepatitis B surface antigen (HBsAg) carriers, those with hepatitis B who have been treated and are stable (HBV DNA < 500 IU/mL), and those who have been cured of hepatitis C may be enrolled.
- •Active autoimmune disease or history of autoimmune disease with potential for relapse.
- •Receipt of corticosteroids (at a dose equivalent to prednisone > 10 mg/day) or other immunosuppressive therapy within 2 weeks prior to study drug administration.
- •History of thyroid dysfunction.
- •Severe chronic or active infection requiring systemic antifungal or antiviral therapy, including tuberculosis infection.
- •History of allergic constitution or allergy to multiple drugs.
- •History of prior pelvic radiotherapy.
- •History of inflammatory bowel disease.
- •Unwillingness to participate or inability to provide written informed consent.
研究组 & 干预措施
Experimental group B
CapOx+Serplulimab+Long-course radiotherapy
干预措施: Moderately Hypofractionated Radiotherapy (Radiation)
Control arm
CapOx+Long-course radiotherapy
干预措施: CapOx+Long-course radiotherapy (Other)
Experimental group A
CapOx+Serplulimab+Moderately Hypofractionated Radiotherapy
干预措施: Serplulimab (Drug)
结局指标
主要结局
Complete Remission (CR) Rate
时间窗: At the time of surgery for pCR, and at 1 year after achieving cCR for sustained cCR
Definition: The proportion of participants achieving complete remission, defined as: Pathologic complete response (pCR): No residual viable tumor cells detected in the resected specimen after neoadjuvant treatment (ypT0N0) Sustained clinical complete response (cCR): No evidence of residual tumor on digital rectal examination, endoscopy, and MRI, maintained for more than 1 year without surgery Assessment Method: Evaluated by investigators based on imaging, endoscopic findings, pathology (for surgical cases), and clinical examination
次要结局
- 3-Year Disease-Free Survival (DFS) Rate(Up to 3 years after randomization)
- 3-Year Overall Survival (OS) Rate(up to 5 years)
- 3-Year Event-Free Survival (EFS) Rate(up to 3 years from treatment)
- Objective Response Rate(Up to 1 years)
- AE rate(24months)
研究者
Xu jianmin
Chief Physician
Fudan University