A Prospective, Randomized, Phase II Trial of MR-guided Adaptive Radiotherapy Combined With PD-1 Antibody and CAPOX for Locally Advanced Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Pathological complete response (pCR) rate
研究概览
简要总结
NeoPulsar is a prospective, randomized phase II trial. 46 LARC (T3-4/N+M0, distance from anal verge ≤12cm) patients will be treated with MR-guided adaptive radiotherapy (30Gy/6Fx) combined with 6 cycles of Toripalimab and CAPOX. TME surgery is scheduled after TNT. The primary endpoint is pathological complete response (pCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, anal function, surgical complication, 3-year LRFS rate, 3-year DFS rate, 3-year OS 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 18-70 years old, male or female
- •Pathologically confirmed rectal adenocarcinoma
- •The distance from anal verge ≤ 10 cm
- •Clinical stage T3-4 and/or N+
- •No evidence of distance metastases
- •MSI/MMR status: MSS/pMMR
- •Karnofsky score >=70
- •Adequate organ function and have no contraindications to surgery, radiochemotherapy, or immunotherapy
- •No chemotherapy or any other anti-tumor therapy prior to enrollment
- •No immunotherapy prior to enrollment
- •With good compliance during the study
- •Signed written informed consent
排除标准
- •Known history of other malignancies within 5 years， except cured skin cancer and cervical cancer in situ
- •Pregnancy or breast-feeding women
- •Individuals with a history of uncontrolled epilepsy, central nervous system disease, or psychiatric disorders that, in the judgment of the investigator, are of such clinical severity that they may prevent the signing of an informed consent form or affect the patient's adherence to oral medications
- •Individuals with clinically serious (i.e., active) heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmia requiring pharmacologic intervention, or history of myocardial infarction within the last 12 months
- •Individuals with a history of organ transplantation requiring immunosuppressive therapy and long-term hormone therapy
- •Individuals with autoimmune diseases
- •Individuals with severe uncontrolled recurrent infections，or other severe uncontrolled concomitant diseases
- •Baseline hematology and biochemistry not meeting the following criteria: Hb≥90g/L; NEU ≥1.5×109/L; PLT ≥100×109/L; ALT, AST ≤2.5 times the upper limit of normal; ALP ≤2.5 times the upper limit of normal; TB <1.5 times the upper limit of normal; Cr <1 time the upper limit of normal; Alb ≥30g/L
- •Individuals with dihydropyrimidine dehydrogenase (DPD) deficiency
- •Individuals allergic to any drug component of the study
研究组 & 干预措施
Group A
The patients will receive conventional pelvic radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.
干预措施: PD-1 antibody (Drug)
Group A
The patients will receive conventional pelvic radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.
干预措施: Oxaliplatin (Drug)
Group A
The patients will receive conventional pelvic radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.
干预措施: Capecitabine (Drug)
Group B
The patients will receive lymph node-sparing radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.
干预措施: PD-1 antibody (Drug)
Group B
The patients will receive lymph node-sparing radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.
干预措施: Oxaliplatin (Drug)
Group B
The patients will receive lymph node-sparing radiotherapy (30Gy/6Fx), combined with 6 cycles of CAPOX and PD-1 antibody. TME surgery is scheduled after TNT.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Pathological complete response (pCR) rate
时间窗: 1 month after the surgery
Rate of pathologic complete response (pCR) after surgery
次要结局
- Grade 3-4 adverse effects rate(From the date of randomization until 3 months after the completion neoadjuvant therapy)
- Anal function(From the date of randomization until 36 months after the surgery)
- Surgical complication(The surgical complications were assessed within 3 months after the surgery)
- 3-year local recurrence free survival (LRFS) rate(From the date of randomization until the date of first documented pelvic failure, assessed up to 36 months)
- 3-year disease free survival (DFS) rate(From the 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 overall survival (OS) rate(From the date of randomization until the date of death from any cause, assessed up to 36 months)
研究者
Zhen Zhang
Study Principal Investigator
Fudan University