A Phase III, Randomized Controlled Study of Neo-adjuvant Toripalimab (JS001) in Combination With Chemotherapy Versus Neo-adjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- Event-free survival (EFS)
研究概览
简要总结
The effect of neo-adjuvant immunochemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas remains unknown. One of our objectives is to evaluate whether the neo-adjuvant immunochemotherapy Toripalimab (JS001) with cisplatin and paclitaxel followed by right thoracic approach esophagectomy with total 2-field lymph node dissection improves the overall survival of thoracic esophageal cancer patients versus neo-adjuvant chemotherapy.
详细描述
The effect of immunochemotherapy in second line treatment of esophageal cancer got a positive results in the world. We tried to apply the immunotheray in resectable esophageal cancer and have planed this phase III clinical trials. The optimal management of resectable esophageal squamous cell carcinomas may have a new chapter in the era of immunotherapy.
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
- •Histologic diagnosis of local advance squamous cell thoracic esophageal carcinoma of Stage (T1N1-3 or T2-3N0-3 M0), (8th Union for International Cancer Control, UICC-TNM).
- •No metastatic lymph node in cervical by color doppler sonography.
- •Patients must not have received any prior anticancer therapy of esophageal carcinoma.
- •Age ranges from 18 to 75 years.
- •Without operative contraindication.
- •Absolute white blood cells count ≥4.0×109/L, neutrophil ≥1.5×109/L, platelets ≥100.0×109/L, hemoglobin ≥90g/L, and normal functions of liver and kidney, total bilirubin（TBIL）≤1.5N, aspartate aminotransferase (AST)≤2.5N, alanine aminotransferase(ALT)≤2.5N, prothrombin time(PT)≤1.5N, and activated partial thromboplastin time(APTT) is in normal range, endogenous creatinine clearance rate(CRE)≤1.5N.
- •Patients must not have diagnosed with other cancer and must not received any prior anticancer therapy except prostatic cancer with more than 5 years disease-free survival(DFS).
- •expected R0 resection.
- •Patients should agree to use contraceptive measures during the study period and within 6 months of the end of the study. Women must be non-lactation.
- •Signed informed consent document on file.
排除标准
- •Multiple primary cancer. 2.Patients with infections disease that require treatment 3.Patients who need continuous hormone treatment 4.unstable angina within 3 months, myocardial infarction within 6 months 5.psychopath 6.Patients with concomitant hemorrhagic disease. 7.Any unexpected reason for patients can't get operation 8.Inability to use gastric conduit after esophagectomy because of a prior surgery.
- •9.Pregnant or breast feeding 10.Patients are diagnosed or suspected to be allergic to cisplatin or Paclitaxel.
- •11.Bronchial asthma who requires intermittent use of bronchodilators or medical interventions 12.Due to co-existing diseases, the immunosuppressant was used. And the dosage of immunosuppressant was more than 10mg/ day orally and more than 2 weeks before enrollment 13.Abnormal coagulation function (PT>16s, APTT>53s, TT>21s, Fib<1.5g/L), tendency of bleeding or receiving thrombolysis or anticoagulant therapy 14.Previous or present pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, lung function severely impaired 15.Autoimmune diseases, immune deficiency, organ transplantation； 16.Hepatitis b/c patients。
研究组 & 干预措施
Neoadjuvant immunochemotherapy
Neo-adjuvant chemotherapy(cisplatin and paclitaxel):
Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles. JS001, 240mg ivgtt, d3, >30min, 3week, 2 cycles
Surgery:
2-3weeks after Neo-adjuvant chemotherapy Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality.
Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included).
After surgery/ maintain period:
JS001, 240mg ivgtt, d3, >30min, 3week (8 cycles at most)
干预措施: Neoadjuvant immunochemotherapy (Drug)
Neoadjuvant chemotherapy
Neo-adjuvant chemotherapy(cisplatin and paclitaxel):
Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles.
Surgery:
2-3weeks after Neo-adjuvant chemotherapy Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality.
Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included).
干预措施: Neoadjuvant immunochemotherapy (Drug)
结局指标
主要结局
Event-free survival (EFS)
时间窗: The date from the beginning of randomization to the date of first record. 5 years EFS
The date from the beginning of randomization to the date of first record of unresectable disease, distant metastases, local recurrences of any causes, and death of any cause.
次要结局
- pCR(within 14 working days after operation)
- OS(5 years OS)
- ORR(3-4 weeks after the last cycle of neoadjuvant treatment)
- R0 resection rate(within 14 working days after operation)
- MPR(within 14 working days after operation)
- NRS-2002(before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation)
- EORTC QLQ-C30(before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation)
- EORTC QLQ-OES18(before surgery, 1month, 3 months, 6 months, 9 months, 1 year after operation)
- DFS(5 years DFS)