SCRT Followed by CAPOX and PD-1 Inhibitor Versus LCCRT Followed by CAPOX in Total Neoadjuvant Treatment for High-risk LARC: A Prospective, Randomized, Multicenter, Phase III Study
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 612
- 试验地点
- 1
- 主要终点
- 3 year event-free survival rate
研究概览
简要总结
In this prospective, multicentre, randomized phase III trial, 612 locally advanced rectal cancer (LARC, T3-4/N+M0) patients with at least one high-risk features (lower location (≤5cm), cT4, cN2, MRF+, EMVI+, TD+) will be included, and randomly assigned to TNT group and iTNT group (1:1). TNT group receives long-course chemoradiotherapy (50Gy/25Fx concurrent with oral capecitabine) followed by 6 cycles of CAPOX. iTNT group receives short-course radiotherapy (25Gy/5Fx) followed by 6 cycles of Serplulimab combined with CAPOX. After the efficacy evaluation, the patients who achieves clinical complete response (cCR) will be managed by a watch and wait (W&W) protocol and non-cCR patients will be recommended surgery. The primary endpoint is 3-year event-free survival rate (3yEFS%). The secondary endpoints include the complete response (CR, pathological complete response [pCR] plus cCR) rate, 3-year organ preservation rate, 3-year disease-free survival rate (3yDFS%), 3-year local recurrence free survival rate (3yLRFS%), 3-year distant metastasis free survival rate (3yDMFS%), 3-year overall survival rate (3yOS%), grade 3-4 acute adverse effects (AE) rate, rate of surgical complications, anal functions and quality of life, 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 old, female and male;
- •Pathological confirmed adenocarcinoma;
- •The distance from anal verge ≤ 10 cm;
- •MSI/MMR status: MSS/pMMR;
- •Clinical stage T3-4 and/or N+, without distance metastases;
- •At least one of the following factors is present: distance from the anus ≤5 cm, cT4, cN2, positive cMRF, positive cEMVI, positive tumor deposit or positive lateral lymph node;
- •No radiotherapy, chemotherapy, immunotherapy, or any other anti-tumor therapy had been administered prior to enrollment;
- •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 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
TNT group
TNT group receives long-course chemoradiotherapy (concurrent with oral capecitabine) followed by 6 cycles of CAPOX.
干预措施: Oxaliplatin (Drug)
TNT group
TNT group receives long-course chemoradiotherapy (concurrent with oral capecitabine) followed by 6 cycles of CAPOX.
干预措施: long-course chemoradiaothearpy (Radiation)
TNT group
TNT group receives long-course chemoradiotherapy (concurrent with oral capecitabine) followed by 6 cycles of CAPOX.
干预措施: Capecitabine (Drug)
iTNT group
iTNT group receives short-course radiotherapy (25Gy/5Fx) followed by 6 cycles of Serplulimab combined with CAPOX.
干预措施: short-course radiaotherapy (Radiation)
iTNT group
iTNT group receives short-course radiotherapy (25Gy/5Fx) followed by 6 cycles of Serplulimab combined with CAPOX.
干预措施: Capecitabine (Drug)
iTNT group
iTNT group receives short-course radiotherapy (25Gy/5Fx) followed by 6 cycles of Serplulimab combined with CAPOX.
干预措施: Oxaliplatin (Drug)
iTNT group
iTNT group receives short-course radiotherapy (25Gy/5Fx) followed by 6 cycles of Serplulimab combined with CAPOX.
干预措施: PD-1 inhibitor (Drug)
结局指标
主要结局
3 year event-free survival rate
时间窗: From date of randomization until the date of first documented early local failure, disease progression during neoadjuvant therapy, pelvic recurrence, distant metastasis, or death, whichever came first, assessed up to 36 months.
Rate of 3 year event free survival
次要结局
- Complete response (CR) rate(1 month after the surgery or the decision of W&W)
- 3 year organ preservation rate(From date of randomization until the resection of rectum or anus, assessed up to 36 months.)
- 3 year disease free survival rate(From date of randomization until the date of first documented recurrence and metastasis after the completion of treatment or 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 distant metastasis free survival rate(From date of randomization until the date of first documented distant metastasis, 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.)
- Grade 3-4 adverse effects rate(From date of randomization until 3 months after the completion neoadjuvant therapy)
- Rate of surgical complications(The surgical complications were assessed within 1 year after the surgery.)
- Low Anterior Resection Syndrome Score(From date of randomization until five years after the completion of treament.)
- Wexner Continence Grading Scale(From date of randomization until five years after the completion of treament.)