A Prospective Phase II Trial of Short-course Radiotherapy Based Total Neoadjuvant Therapy Combined With PD-1 Inhibitor for Locally Advanced Rectal Cancer (TORCH）
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 130
- 试验地点
- 3
- 主要终点
- Complete response (CR) rate
研究概览
简要总结
TORCH is a prospective, multicentre, randomized phase II trial. 130 LARC (T3-4/N+M0, distance from anal verge ≤12cm) patients will be treated with total neoadjuvant therapy (TNT) and assigned to Group A and Group B. Group A receives SCRT (25Gy/5Fx) followed by 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Group B receives 2 cycles of ToriCAPOX followed by SCRT and 4 cycles of ToriCAPOX. 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, 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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathological confrmed adenocarcinoma
- •Clinical stage T3-4 and/or N+
- •The distance from anal verge ≤12 cm
- •Without distance metastases
- •Age 18-70 years old, female and male
- •Baseline blood and biochemical indicators meet the following criteria: neutrophils≥1.5×10^9/L, Hb≥90 g/L, PLT≥100×10^9/L, ALT/AST≤2.5 ULN, Cr≤1 ULN
- •With good compliance and signed the consent form
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 immunodefciencies, known history of organ transplantation or systematic use of immunosuppressive agents
- •Known history of human immunodefciency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection
- •Active Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (i.e., HBsAg positive or HBV DNA positive, HCV RNA positive if anti-HCV antibody testing positive)
- •Allergic to any component of the therapy
研究组 & 干预措施
Group A
The patients will receive short-course radiotherapy (25Gy/5Fx), followed by 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
干预措施: PD-1 antibody (Drug)
Group A
The patients will receive short-course radiotherapy (25Gy/5Fx), followed by 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
干预措施: Capecitabine (Drug)
Group A
The patients will receive short-course radiotherapy (25Gy/5Fx), followed by 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
干预措施: Oxaliplatin (Drug)
Group A
The patients will receive short-course radiotherapy (25Gy/5Fx), followed by 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
干预措施: Short-course radiotherapy (Radiation)
Group B
The patients will firstly receive 2 cycles of CAPOX and PD-1 antibody, then receive short-course radiotherapy (25Gy/5Fx), followed by 4 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
干预措施: PD-1 antibody (Drug)
Group B
The patients will firstly receive 2 cycles of CAPOX and PD-1 antibody, then receive short-course radiotherapy (25Gy/5Fx), followed by 4 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
干预措施: Capecitabine (Drug)
Group B
The patients will firstly receive 2 cycles of CAPOX and PD-1 antibody, then receive short-course radiotherapy (25Gy/5Fx), followed by 4 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
干预措施: Oxaliplatin (Drug)
Group B
The patients will firstly receive 2 cycles of CAPOX and PD-1 antibody, then receive short-course radiotherapy (25Gy/5Fx), followed by 4 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT while a W&W option can be applied to patients achieving cCR.
干预措施: Short-course radiotherapy (Radiation)
结局指标
主要结局
Complete response (CR) rate
时间窗: The status of cCR will be evaluated after the completion of neoadjuvant therapy. The pCR rate will be evaluated after surgery. The cCR patients who adopted W&W strategy will be included into the CR rate caluculation.
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
- 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.)
- Rate of Surgical complications(The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 5 years from the surgery.)
- Scores of Quality of Life(From date of randomization until the date of death from any cause, assessed up to 10 years)
- Grade 3-4 adverse effects rate(From date of randomization until the date of death from any cause, assessed up to 5 years)
- 3 year overall survival rate(From date of randomization until the date of death from any cause, assessed up to 36 months.)