Clinical Exploration of Involved-field Radiotherapy-TNT Combined With PD-1 Inhibitor for pMMR Locally Advanced Rectal Cancer: a Prospective, Open-label, Randomized Controlled Trial (Neo-Field I)
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- CR rate
研究概览
简要总结
The purpose of this study is to explore the efficacy and safety of involved-field radiotherapy-TNT combined with PD-1 inhibitors in pMMR locally advanced rectal cancer.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years old, male or female;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
- •Pathologic diagnosis of adenocarcinoma of the rectum, definite pMMR type;
- •Clinical staging of T3-4NanyM0 or T1-2N+M0 (based on AJCC 8th edition staging criteria);
- •The lower margin of the primary tumor is located below the peritoneal reflex or the lower margin of the tumor is ≤10 cm from the anal verge;
- •Pre-enrollment laboratory indicators meet the following indicator ranges： 1)Blood: absolute neutrophils ≥1.5×10^9/L, platelets ≥100×10^9/L, hemoglobin ≥90g/L; 2)Liver and kidney function: ALT/AST ≤ 2.5 x ULN, total bilirubin ≤ 1.5 x ULN, creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60mL/min (Cockcroft-Gault formula)； 3)Coagulation: INR ≤ 1.5, APTT ≤ 1.5 x ULN (for those not receiving anticoagulation)；
- •Women or men of childbearing potential need to agree to use effective contraception during the study and for 6 months after the last treatment session;
- •Voluntary written informed consent and commitment to complete the full treatment and follow-up program.
排除标准
- •Pathologic type is other specific types such as neuroendocrine carcinoma, squamous carcinoma, etc;
- •Previous radiotherapy, chemotherapy, targeted or immunotherapy for rectal cancer;
- •Active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis requiring long-term immunosuppressive therapy)；
- •Presence of active infection (e.g. HIV, HBV/HCV viral load positive requiring stabilization on antiretroviral therapy)；
- •Severe cardiovascular disease (e.g., myocardial infarction within 6 months, unstable angina, uncontrolled hypertension >160/100 mmHg)；
- •History of other malignant tumors (except non-melanoma skin cancers, cervical cancer in situ, etc. cured for ≥5 years)；
- •Uncontrolled diabetes mellitus (HbA1c > 8%), abnormal thyroid function (TSH outside normal range and requiring pharmacologic intervention)；
- •Severe chronic bowel disease (e.g., Crohn's disease, active ulcerative colitis)； Patients deemed by the investigator to be unsuitable for participation in this study.
研究组 & 干预措施
Involve-field radiotherapy-TNT+Camrelizumab
Patients received Involve-field radiotherapy (25Gy/5f, including the primary rectal tumor, metastatic or suspected pelvic lymph nodes, mesorectal, and presacral regions). Four cycles of CAPOX plus Carilizumab were given to patients 1-2 weeks after chemoradiotherapy completion.
Patients were evaluated 2-3 weeks after the end of treatment. Patients who met the cCR criteria could choose to undergo surgical treatment or not. For patients who did not meet the cCR criteria, surgical treatment was recommended. For patients who refused surgery, the patients in the trial group continued to receive 4 cycles of CAPOX chemotherapy combined with camrelizumab.
干预措施: CAPOX (Drug)
Involve-field radiotherapy-TNT+Camrelizumab
Patients received Involve-field radiotherapy (25Gy/5f, including the primary rectal tumor, metastatic or suspected pelvic lymph nodes, mesorectal, and presacral regions). Four cycles of CAPOX plus Carilizumab were given to patients 1-2 weeks after chemoradiotherapy completion.
Patients were evaluated 2-3 weeks after the end of treatment. Patients who met the cCR criteria could choose to undergo surgical treatment or not. For patients who did not meet the cCR criteria, surgical treatment was recommended. For patients who refused surgery, the patients in the trial group continued to receive 4 cycles of CAPOX chemotherapy combined with camrelizumab.
干预措施: Involve-field irradiation (Radiation)
Involve-field radiotherapy-TNT+Camrelizumab
Patients received Involve-field radiotherapy (25Gy/5f, including the primary rectal tumor, metastatic or suspected pelvic lymph nodes, mesorectal, and presacral regions). Four cycles of CAPOX plus Carilizumab were given to patients 1-2 weeks after chemoradiotherapy completion.
Patients were evaluated 2-3 weeks after the end of treatment. Patients who met the cCR criteria could choose to undergo surgical treatment or not. For patients who did not meet the cCR criteria, surgical treatment was recommended. For patients who refused surgery, the patients in the trial group continued to receive 4 cycles of CAPOX chemotherapy combined with camrelizumab.
干预措施: TME surgery (Procedure)
Elective nodal irradiation-TNT
Patients received elective nodal long-course concurrent chemoradiotherapy (50.4 Gy/28f). Capecitabine (825 mg/m² bid) was administered orally on radiotherapy days. Four cycles of CAPOX were given to patients 1-2 weeks after chemoradiotherapy completion.
Patients were evaluated 2-3 weeks after the end of treatment. Patients who met the cCR criteria could choose to undergo surgical treatment or not. For patients who did not meet the cCR criteria, surgical treatment was recommended. For patients who refused surgery, the patients in the trial group continued to receive 4 cycles of CAPOX chemotherapy.
干预措施: CAPOX (Drug)
Elective nodal irradiation-TNT
Patients received elective nodal long-course concurrent chemoradiotherapy (50.4 Gy/28f). Capecitabine (825 mg/m² bid) was administered orally on radiotherapy days. Four cycles of CAPOX were given to patients 1-2 weeks after chemoradiotherapy completion.
Patients were evaluated 2-3 weeks after the end of treatment. Patients who met the cCR criteria could choose to undergo surgical treatment or not. For patients who did not meet the cCR criteria, surgical treatment was recommended. For patients who refused surgery, the patients in the trial group continued to receive 4 cycles of CAPOX chemotherapy.
干预措施: Elective nodal irradiation (Radiation)
Elective nodal irradiation-TNT
Patients received elective nodal long-course concurrent chemoradiotherapy (50.4 Gy/28f). Capecitabine (825 mg/m² bid) was administered orally on radiotherapy days. Four cycles of CAPOX were given to patients 1-2 weeks after chemoradiotherapy completion.
Patients were evaluated 2-3 weeks after the end of treatment. Patients who met the cCR criteria could choose to undergo surgical treatment or not. For patients who did not meet the cCR criteria, surgical treatment was recommended. For patients who refused surgery, the patients in the trial group continued to receive 4 cycles of CAPOX chemotherapy.
干预措施: TME surgery (Procedure)
Elective nodal irradiation-TNT
Patients received elective nodal long-course concurrent chemoradiotherapy (50.4 Gy/28f). Capecitabine (825 mg/m² bid) was administered orally on radiotherapy days. Four cycles of CAPOX were given to patients 1-2 weeks after chemoradiotherapy completion.
Patients were evaluated 2-3 weeks after the end of treatment. Patients who met the cCR criteria could choose to undergo surgical treatment or not. For patients who did not meet the cCR criteria, surgical treatment was recommended. For patients who refused surgery, the patients in the trial group continued to receive 4 cycles of CAPOX chemotherapy.
干预措施: Capecitabine (Drug)
Involve-field radiotherapy-TNT+Camrelizumab
Patients received Involve-field radiotherapy (25Gy/5f, including the primary rectal tumor, metastatic or suspected pelvic lymph nodes, mesorectal, and presacral regions). Four cycles of CAPOX plus Carilizumab were given to patients 1-2 weeks after chemoradiotherapy completion.
Patients were evaluated 2-3 weeks after the end of treatment. Patients who met the cCR criteria could choose to undergo surgical treatment or not. For patients who did not meet the cCR criteria, surgical treatment was recommended. For patients who refused surgery, the patients in the trial group continued to receive 4 cycles of CAPOX chemotherapy combined with camrelizumab.
干预措施: Camrelizumab (Drug)
结局指标
主要结局
CR rate
时间窗: within 5 weeks
CR defined as patient achieving pCR and cCR.
次要结局
- MPR rate(within 3 weeks after surgery)
- R0-resection rate(within 3 weeks after surgery)
- Preservation rate of adjacent invaded organs(within 3 weeks after surgery)
- ORR(within 5 weeks)
- 3-year Event Free Survival(3 years)
- 3-year OS(3 years)
- Incidence of adverse reactions(1 year)