Phase II Study of Toripalimab Combined With Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel (FLOT) in Patients With Locally Advanced, Resectable Gastric Cancer or Gastroesophageal Junction Adenocarcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Pathological complete response rate (pCR)
研究概览
简要总结
Gastric cancer is one of the most common malignant tumors of the digestive tract. Gastric cancer patients diagnosed for the first time in China have a higher proportion of advanced stages and a higher postoperative metastasis rate. Studies have shown that patients with good pathological response after preoperative neoadjuvant therapy (such as tumor regression grade, TRG0 or 1) have a better prognosis. The AIO-FLOT4 study found that preoperative perioperative FLOT chemotherapy not only prolonged the progression-free survival (PFS) time and overall survival (OS) time of patients with advanced gastric cancer, but also increased postoperative pathological remission rate. How to further improve the efficacy of the perioperative treatment plan may be beneficial to improve the long-term survival of gastric cancer patients. Several clinical studies have also confirmed that PD-1 antibody significantly prolongs the life of gastric cancer patients who have failed advanced chemotherapy in the back-line treatment. Thus the investigators plan to conduct this clinical trials to evaluate the safety and efficacy of Toripalimab (PD-1 antibody) combined with FLOT regimen in the perioperative period.The secondary end points included pathological remission rate, resection rate, D2 radical resection rate, 5-year disease-free survival (DFS) rate and 5-year OS rate.
详细描述
Gastric cancer is one of the most common malignant tumors of the digestive tract, accounting for the second incidence of malignant tumors, and the third mortality factor related to malignant tumors. In China, most patients with gastric cancer diagnosed for the first time are already in the advanced stage, with stage II and III patients accounting for 63%, and the postoperative recurrence rate is higher. Studies have shown that patients with good pathological response after preoperative neoadjuvant therapy (such as TRG0 or 1) have a better prognosis. In recent years, the AIO-FLOT4 study have found that perioperative chemotherapy with FLOT regimen has prolonged the PFS and OS in patients with advanced gastric cancer. It is preferred to recommend perioperative chemotherapy with FLOT regimen for patients with advanced gastric cancer in the NCCN guidelines or Chinese CSCO guidelines. How to further improve the efficacy of the perioperative treatment plan may be beneficial to improve the long-term survival of gastric cancer patients.
Several clinical studies have also confirmed that PD-1 antibody significantly prolongs the life of gastric cancer patients who have failed advanced chemotherapy in the back-line treatment. In the KEYNOTE-059 study, the effectiveness of chemotherapy combined with PD-1 antibody in gastric cancer patients newly treated reached 62%. It is necessary to explore the efficacy of PD-1 antibody combined with FLOT regimen in the perioperative period. Thus the investigators plan to conduct this clinical trials to evaluate the safety and efficacy of Toripalimab (PD-1 antibody) combined with FLOT regimen in the perioperative period.The secondary end points included pathological remission rate, resection rate, D2 radical resection rate, 5-year DFS rate and 5-year OS rate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •locally advanced (>T1) and/or nodal positive (N+) histologically proven adenocarcinoma of the gastric or gastroesophageal junction without distant metastases (M0)
- •no previous surgical resection
- •no previous cytostatic chemotherapy
- •Age > 18 years, no more than 75 years (female and male)
- •Karnofsky Performance Status score of physical condition is 80-100
- •surgical resectability
- •Exclusion of peritoneal carcinomatosis (if clinically suspected) via laparoscopy
- •Leucocytes > 4.000/µl
- •Platelets > 100.000/µl
- •Serum creatinin ≤ 1.5x of normal value, or Creatinin-Clearance > 50 ml/min
- •written informed consent.
排除标准
- •Distant metastasis or local invasion of adjacent organs;
- •Recurrent or residual gastric cancer;
- •Having or having had autoimmune disease;
- •Previous organ transplantation or HIV patients;
- •Allergy or contraindications to Toripalimab, 5- Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel;
- •Malignant secondary disease;
- •Severe non-surgical disease or acute infection;
- •Peripheral polyneuropathy > NCI grad I;
- •Blood system, liver and kidney function were damaged;
- •Symptomatic brain metastasis;
- •Obvious arrhythmia, myocardial ischemia, severe atrioventricular block, cardiac insufficiency and severe gravity valve disease;
- •Psychotic subjects who are not easy to control;
- •Pregnant or lactating subjects.
研究组 & 干预措施
Toripalimab combined with FLOT
In the perioperative period, patients with resectable gastric cancer is treated with flot regimen combined with Toripalimab to observe whether the 3-year disease-free survival (DFS) rate, pathological remission rate, R0 resection rate, D2 radical resection rate, 5-year DFS rate and 5-year OS rate could be improved.
干预措施: Toripalimab (Drug)
Toripalimab combined with FLOT
In the perioperative period, patients with resectable gastric cancer is treated with flot regimen combined with Toripalimab to observe whether the 3-year disease-free survival (DFS) rate, pathological remission rate, R0 resection rate, D2 radical resection rate, 5-year DFS rate and 5-year OS rate could be improved.
干预措施: Fluorouracil (Drug)
Toripalimab combined with FLOT
In the perioperative period, patients with resectable gastric cancer is treated with flot regimen combined with Toripalimab to observe whether the 3-year disease-free survival (DFS) rate, pathological remission rate, R0 resection rate, D2 radical resection rate, 5-year DFS rate and 5-year OS rate could be improved.
干预措施: Docetaxel (Drug)
Toripalimab combined with FLOT
In the perioperative period, patients with resectable gastric cancer is treated with flot regimen combined with Toripalimab to observe whether the 3-year disease-free survival (DFS) rate, pathological remission rate, R0 resection rate, D2 radical resection rate, 5-year DFS rate and 5-year OS rate could be improved.
干预措施: Leucovorin (Drug)
Toripalimab combined with FLOT
In the perioperative period, patients with resectable gastric cancer is treated with flot regimen combined with Toripalimab to observe whether the 3-year disease-free survival (DFS) rate, pathological remission rate, R0 resection rate, D2 radical resection rate, 5-year DFS rate and 5-year OS rate could be improved.
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Pathological complete response rate (pCR)
时间窗: Up to 6 months
Proportion of patients with gastric cancer who received Toripalimab combined with FLOT regimen after 4 cycles of neoadjuvant therapy and postoperative pathological examination TRG 0
3-year Disease-Free Survival Rate
时间窗: Up to 3 years
The primary end point of the study is the effect of perioperative time flot regimen combined with Toripalimab and D2 radical operation on the 3-year disease-free survival time of resectable gastric cancer.
次要结局
- Major pathological (complete and nearly complete) response (MPR)(Up to 6 months)
- Adverse Events(Up to 6 months)
- 5-year Disease-Free Rate(Up to 5 years)
- 5-year Survival Rate(Up to 5 years)