Pd1 Antibody Sintilimab ± Chemoradiotherapy for Locally Advanced Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 195
- 试验地点
- 1
- 主要终点
- complete response rate
研究概览
简要总结
In this study, participants with locally advanced rectal cancer patients will be treated according to MMR/MSI status. There will be two cohorts in this study: Cohort A and Cohort B. For Cohort A, dMMR or MSI-H patients will receive 4 cycles of neoadjuvant Pd1 antibody Sintilimab,followed by one of the following treatments: (1) surgery and adjuvant treatment, (2）another 4 cycles of sintilimab, followed by radical surgery or observation (only for cCR) . For Cohort B, pMMR/MSS/MSI-L patients will be randomized to receive neoadjuvant chemoradiotherapy ± four cycles of Pd1 antibody Sintilimab，followed by one of the following treatments: (1) curative surgery and four cycles of adjuvant chemotherapy;(2)four cycles of chemotherapy then observation (only cCR after neoadjuvant therapy)
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
- •Histologically proven colorectal adenocarcinoma;
- •Cohort 1: Biopsy tissues with IHC indicates deficient mismatch repair(dMMR),that is,the loss of at least one of the four proteins ,MSH1,MSH2,MSH6,PMS2;or gene detection implies MSI-H; Cohort 2: Biopsy tissues with IHC indicates proficient mismatch repair(pMMR),that is positivity of all four proteins ,MSH1,MSH2,MSH6,PMS2;or gene detection implies MSS/MSI-L
- •Clinical stage for rectal cancer patients is cT3-4N0M0 or cTxN+M0;
- •Preoperative staging methods: all patients need to accept digital rectal examination(DRE).Patients with rectal cancer undergo high-resolution MRI±ultrasound colonoscopy/transrectal ultrasound for preoperative staging. Perienteric lymph nodes with short diameter ≥10mm or the shape of lymph nodes and its MRI characteristics are consistent with typical lymph node metastasis. If endoscopic ultrasonography is used in combination, and there is a contradiction between staging methods, the data should be submitted to the evaluation team of our center for the accurate staging;
- •No symptoms of ileus; or ileus is alleviated after proximal colostomy.
- •No rectal surgery except preventative stoma;
- •No chemotherapy or radiotherapy;
- •No biotherapy (e.g.monoclonal antibodies), immunotherapy (e.g.anti-PD-1 antibody,anti-PD-L1 antibody,anti-PD-L2 antibody or CTLA-4 antibody),or other clinical trials agents;
- •No limit to previous endocrine therapy.
- •Age between 18 and 75 years;
- •ECOG performance status of 0 or 1;
- •Life expectancy: more than 2 years;
- •Hematopoietic: WBC>3×109/L;PLT>80×109/L; Hb>90g/L;
- •Hepatic: ALT and AST<2 times upper limit of normal (ULN); bilirubin<1.5 times ULN;
- •Renal: creatinine <1.5 times ULN or creatinine clearance ≥ 60 mL/min.
排除标准
- •Arrhythmias require antiarrhythmic therapy (with the exception of β-blockers or digoxin), symptomatic coronary artery disease or local myocardial ischemia (myocardial infarction within the past 6 months) or congestive heart failure exceeding NYHA II;
- •Severe hypertension with poor control after medication;
- •A known history of testing positive for HIV or chronic hepatitis B or C (high copy virus DNA) at active stage;
- •Patients with active tuberculosis (TB) are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening;
- •Other active severe clinical infections (NCI-CTC5.0);
- •Apparent distant metastasis away from the pelvic before surgery;
- •Cachexia, organ function decompensation;
- •Previous pelvic or abdominal radiotherapy;
- •Multiple primary colorectal cancers;
- •Epilepsy require medical treatment (such as steroid or antiepileptic therapy);
- •Other malignancy within the past 5 years with the exception of effectively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin;
- •Drug abuse and medical, psychological or social factors that may interfere with patients' participation in the study or affect the evaluation of the study;
- •Patients have any active autoimmune diseases or a history of autoimmune diseases(including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism and decreased thyroid function; patients with vitiligo or with complete remission of asthma in childhood and without any intervention in adulthood may be included; patients with asthma requiring bronchodilators intervention are not included.
- •Received any anti-infection vaccine (e.g. influenza vaccine, chickenpox vaccine, etc.) within 4 weeks before enrollment;
- •Complications require long-term treatment with immunosuppressive drugs, or requiring systemic or local use of immunosuppressive corticosteroids(>10mg/day prednisone or other therapeutic hormones);
- •Known or suspected allergy to the study drugs or to any drugs related to this trial;
- •Any unstable condition or which endangers the patients' safety and compliance;
- •Pregnant or breast-feeding women who are fertile without effective contraception;
- •Refuse to sign the informed consent.
研究组 & 干预措施
Cohort A
After 4 cycles of neoadjuvant sintilimab treatment, the patients and doctors could choose one of the following treatments: (1) surgery, followed by 4 cycles of adjuvant sintilimab with or without Capeox chemotherapy; (2) another 4 cycles of sintilimab, followed by radical surgery or observation (only for patients with clinical complete response).
干预措施: Oxaliplatin (Drug)
Cohort A
After 4 cycles of neoadjuvant sintilimab treatment, the patients and doctors could choose one of the following treatments: (1) surgery, followed by 4 cycles of adjuvant sintilimab with or without Capeox chemotherapy; (2) another 4 cycles of sintilimab, followed by radical surgery or observation (only for patients with clinical complete response).
干预措施: Capecitabine (Drug)
Cohort A
After 4 cycles of neoadjuvant sintilimab treatment, the patients and doctors could choose one of the following treatments: (1) surgery, followed by 4 cycles of adjuvant sintilimab with or without Capeox chemotherapy; (2) another 4 cycles of sintilimab, followed by radical surgery or observation (only for patients with clinical complete response).
干预措施: Sintilimab (Drug)
Cohort A
After 4 cycles of neoadjuvant sintilimab treatment, the patients and doctors could choose one of the following treatments: (1) surgery, followed by 4 cycles of adjuvant sintilimab with or without Capeox chemotherapy; (2) another 4 cycles of sintilimab, followed by radical surgery or observation (only for patients with clinical complete response).
干预措施: total mesorectal excision (Procedure)
Cohort A
After 4 cycles of neoadjuvant sintilimab treatment, the patients and doctors could choose one of the following treatments: (1) surgery, followed by 4 cycles of adjuvant sintilimab with or without Capeox chemotherapy; (2) another 4 cycles of sintilimab, followed by radical surgery or observation (only for patients with clinical complete response).
干预措施: Watch and wait (Other)
Cohort B-arm 1
After four cycles of neoadjuvant Sintilimab, Capeox and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)
干预措施: Oxaliplatin (Drug)
Cohort B-arm 1
After four cycles of neoadjuvant Sintilimab, Capeox and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)
干预措施: Capecitabine (Drug)
Cohort B-arm 1
After four cycles of neoadjuvant Sintilimab, Capeox and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)
干预措施: Sintilimab (Drug)
Cohort B-arm 1
After four cycles of neoadjuvant Sintilimab, Capeox and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)
干预措施: radiotherapy (Radiation)
Cohort B-arm 1
After four cycles of neoadjuvant Sintilimab, Capeox and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)
干预措施: total mesorectal excision (Procedure)
Cohort B-arm 1
After four cycles of neoadjuvant Sintilimab, Capeox and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)
干预措施: Watch and wait (Other)
Cohort B-arm 2
After four cycles of neoadjuvant Capeox chemotherapy and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)
干预措施: Oxaliplatin (Drug)
Cohort B-arm 2
After four cycles of neoadjuvant Capeox chemotherapy and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)
干预措施: Capecitabine (Drug)
Cohort B-arm 2
After four cycles of neoadjuvant Capeox chemotherapy and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)
干预措施: radiotherapy (Radiation)
Cohort B-arm 2
After four cycles of neoadjuvant Capeox chemotherapy and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)
干预措施: total mesorectal excision (Procedure)
Cohort B-arm 2
After four cycles of neoadjuvant Capeox chemotherapy and radiotherapy, the patients and doctors could choose one of the following treatments: (1) curative surgery and four cycles of adjuvant Capeox chemotherapy;(2)four cycles of Capeox chemotherapy then observation (only for patients with clinical complete response after neoadjuvant therapy)
干预措施: Watch and wait (Other)
结局指标
主要结局
complete response rate
时间窗: 6 weeks after curative surgery for pCR; 6 weeks after the completion of neoadjuvant therapy for cCR
the proportion of CR cases (pCR for those who underwent surgery and cCR for those who didn't receive surgery)
次要结局
- Local recurrence(5 years after curative surgery)
- Acute toxiticy according CTCAE5.0(From start of treatment to 3 months after the adjuvant therapy or last dose of treatment)
- Tumor regresssion grade according to AJCC TRG grading system(6 weeks after curative surgery)
- R0 resection rate(6 weeks after curative surgery)
- Distant metastasis(5 years after curative surgery)
- Tumor response(6 weeks after first study treatment)
研究者
Ruihua Xu
Professor
Sun Yat-sen University