A Prospective Randomized Phase II Trial of Long-Course Chemoradiotherapy or Short-Course Radiotherapy Combined With CAPOX, PD-1 Antibody, and a COX-2 Inhibitor for Microsatellite Stable Locally Advanced Rectal Cancer (SERRAC)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- Complete response (CR) rate
研究概览
简要总结
SERRAC is a prospective, multicentre, randomized phase II trial. 138 LARC (T3-4/N+M0, distance from anal verge ≤10cm) patients will be treated with neoadjuvant therapy and assigned to Group A and Group B (1:1). Group 1 receives LCRT (50Gy/25Fx) followed by 3 cycles of CAPOX.Group 2 receives SCRT (25Gy/5Fx) followed by 4 cycles of capecitabine plus oxaliplatin (CAPOX) chemotherapy and PD-1 antibody. The COX2 inhibitor celecoxib 200 mg was started orally twice a day during chemotherapy until the end of neoadjuvant treatment.TME surgery is scheduled after TNT while a watch and wait (W&W) option can be applied to patients achieving clinical complete response (cCR). The primary endpoint is complete response (CR, pathological complete response [pCR] plus cCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, anal preservation rate, 3-year DFS rate, etc.
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, gender not limited
- •Pathologically confirmed rectal adenocarcinoma
- •≤10 cm from the anus
- •Baseline stage T3-4/N+
- •No distant metastasis
- •MSI/MMR status MSS/pMMR
- •Karnofsky performance status score ≥70
- •No prior chemotherapy or other anti-cancer treatment prior to enrollment
- •No prior immunotherapy prior to enrollment
- •Ability to comply with the study protocol
- •Written informed consent
排除标准
- •Pregnancy or breast-feeding women;
- •Known history of other malignancies within 5 years;
- •Known history of previous anti-tumor treatment, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T cell-related therapy, etc;
- •Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);
- •Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;
- •Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;
- •Uncontrolled infection which needs systemic therapy;
- •Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;
- •Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection
- •Allergic to any component of the therapy.
研究组 & 干预措施
Long-course Radiotherapy plus chemotherapy group
干预措施: Serplulimab (Drug)
Short-course Radiotherapy plus immunochemotherapy group
干预措施: Oxaliplatin (Drug)
Short-course Radiotherapy plus immunochemotherapy group
干预措施: Capecitabine (Drug)
Short-course Radiotherapy plus immunochemotherapy group
干预措施: Celecoxib (Drug)
Short-course Radiotherapy plus immunochemotherapy group
干预措施: Short-course radiotherapy (Radiation)
Short-course Radiotherapy plus immunochemotherapy group
干预措施: Serplulimab (Drug)
Long-course Radiotherapy plus chemotherapy group
干预措施: Long-course radiotherapy (Radiation)
Long-course Radiotherapy plus chemotherapy group
干预措施: Oxaliplatin (Drug)
Long-course Radiotherapy plus chemotherapy group
干预措施: Capecitabine (Drug)
Long-course Radiotherapy plus chemotherapy group
干预措施: Celecoxib (Drug)
结局指标
主要结局
Complete response (CR) rate
时间窗: 1 month after the surgery or the decision of W&W
Rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of cCR with W\&W strategy.
次要结局
- Grade 3-4 adverse effects rate(From date of randomization until 3 months after the completion neoadjuvant therapy)
- 3 year anal preservation rate(From date of randomization until the date of or date of death from any cause, whichever came first, assessed up to 36 months.)
- 3 year disease free survival rate(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.)
- 3 year local recurrence free survival rate(From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.)
- 3 year overall survival rate(From date of randomization until the date of death from any cause, assessed up to 36 months.)
- Rate of surgical complications(The surgical complications were assessed within 3 months after the surgery.)