A Randomized Phase II Study of Long-term Chemoradiotherapy or Short-term Radiotherapy Combined With CAPOX, PD-1 Monoclonal Antibody and COX-2 Inhibitors in MSS Type Locally Advanced Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 138
- 试验地点
- 5
- 主要终点
- CR (Complete Response)
研究概览
简要总结
This randomized phase II trial evaluates the efficacy of long-course chemoradiotherapy (50Gy/25Fx + capecitabine) versus short-course radiotherapy (25Gy/5Fx) combined with CAPOX（Capecitabine and Oxaliplatin）, PD-1 inhibitor (serplulimab), and COX-2 inhibitor (celecoxib) in MSS（MicroSatellite Stable） locally advanced rectal cancer, with primary endpoint of complete response rate (pCR+cCR)（Complete Remission） and secondary endpoints including anal preservation rate and 3-year survival outcomes, aiming to elucidate the immunomodulatory effects of triple therapy on tumor microenvironment.
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 18-75 years, regardless of gender.
- •Pathologically confirmed rectal adenocarcinoma.
- •Tumor located ≤10 cm from the anal verge.
- •Baseline stage T3-4 and/or N+ (locally advanced disease).
- •No evidence of distant metastasis.
- •Microsatellite stability (MSS) or proficient mismatch repair (pMMR).
- •Karnofsky Performance Status (KPS) ≥
- •No prior chemotherapy or any other anticancer therapy before enrollment.
- •No prior immunotherapy.
- •Able to comply with study protocol requirements throughout the study period.
- •Signed written informed consent obtained prior to study participation.
排除标准
- •Pregnant or lactating women.
- •Individuals with a history of other malignant diseases within the past 5 years, excluding cured skin cancer and cervical carcinoma in situ.
- •Individuals with a history of uncontrolled epilepsy, central nervous system diseases, or mental disorders, where the clinical severity (as judged by the investigator) may impair the ability to sign the informed consent form or affect compliance with oral medication.
- •Clinically significant (i.e., active) heart disease, including symptomatic coronary heart disease, congestive heart failure of New York Heart Association (NYHA) class II or worse, severe arrhythmias requiring pharmacological intervention, or a history of myocardial infarction within the past 12 months.
- •Individuals requiring immunosuppressive therapy for organ transplantation and those on long-term corticosteroid therapy.
- •Individuals with autoimmune diseases.
- •Individuals with severe, uncontrolled, recurrent infections or other severe, uncontrolled concurrent diseases.
- •Baseline blood routine and biochemical parameters not meeting the following criteria: hemoglobin ≥90 g/L; absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelets ≥100×10⁹/L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× upper limit of normal (ULN); alkaline phosphatase (ALP) ≤2.5×ULN; serum total bilirubin <1.5×ULN; serum creatinine <1×ULN; serum albumin ≥30 g/L.
- •Individuals with known dihydropyrimidine dehydrogenase (DPD) deficiency. Individuals with a history of hypersensitivity to any component of the study medications.
研究组 & 干预措施
Long-course chemoradiotherapy group
The long-course chemoradiotherapy (LC-CRT) arm refers to a preoperative treatment regimen combining normofractionated radiotherapy with concurrent chemotherapy.
干预措施: LCRT (Radiation)
Long-course chemoradiotherapy group
The long-course chemoradiotherapy (LC-CRT) arm refers to a preoperative treatment regimen combining normofractionated radiotherapy with concurrent chemotherapy.
干预措施: CAPOX (Drug)
Long-course chemoradiotherapy group
The long-course chemoradiotherapy (LC-CRT) arm refers to a preoperative treatment regimen combining normofractionated radiotherapy with concurrent chemotherapy.
干预措施: PD-1 (Drug)
Long-course chemoradiotherapy group
The long-course chemoradiotherapy (LC-CRT) arm refers to a preoperative treatment regimen combining normofractionated radiotherapy with concurrent chemotherapy.
干预措施: Celecoxib (Drug)
Short-course chemoradiotherapy group
The short-course chemoradiotherapy group refers to a preoperative regimen combining hypofractionated radiotherapy with concurrent or sequential chemotherapy .
干预措施: SCRT (Radiation)
Short-course chemoradiotherapy group
The short-course chemoradiotherapy group refers to a preoperative regimen combining hypofractionated radiotherapy with concurrent or sequential chemotherapy .
干预措施: CAPOX (Drug)
Short-course chemoradiotherapy group
The short-course chemoradiotherapy group refers to a preoperative regimen combining hypofractionated radiotherapy with concurrent or sequential chemotherapy .
干预措施: PD-1 (Drug)
Short-course chemoradiotherapy group
The short-course chemoradiotherapy group refers to a preoperative regimen combining hypofractionated radiotherapy with concurrent or sequential chemotherapy .
干预措施: Celecoxib (Drug)
结局指标
主要结局
CR (Complete Response)
时间窗: 3 years
Complete response (CR) in malignant tumor patients is defined as the complete disappearance of all target lesions, normalization of tumor marker levels, and absence of new lesions for ≥4 weeks after treatment.
次要结局
- sphincter preservation rate(3 years)
- Grade 3 or higher toxicity rate(3 years)
- 3yPFS (Progression-Free Survival)(3 years)
- 3yLRFS (Local Recurrence-Free Survival)(3 years)
- 3yOS (Overall Survival)(3 years)
- Surgical complications(3 years)