Perioperative Chemotherapy With FOLFIRINOX Regimen or FLOT Regimen for Resectable Gastric or Esophagogastric Junction Adenocarcinoma (Type II-III): Open-label Randomized Phase 2/3 Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 538
- 试验地点
- 1
- 主要终点
- median overall survival
研究概览
简要总结
Patients with resectable adenocarcinoma of the stomach or the esophagogastric junction (II-III type by Siewert) without previous therapy will be treated with one of two chemotherapy combinations before and after surgery. One half of the patients gets 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin and Docetaxel (FLOT), the others 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin and Irinotecan (FOLFIRINOX). Main objective of the study is median overall survival.
详细描述
538 Patients with resectable (cT4cN0 or cT1-4 and cN+, cM0) adenocarcinoma of the stomach or the esophagogastric junction without previous therapy will be included in this study. After randomization patients receive perioperatively 4 cycles FLOT or FOLFIRINOX, followed by a restaging of the tumour status and surgery. Subsequently another 4 cycles of FLOT or FOLFIRNOX are applicated.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •сT4 cN0 or cT1-4 cN+ histologically proven adenocarcinoma of the esophagogastric junction (Siewert type II-III) or the stomach without distant metastases (M0)
- •No previous cytostatic chemotherapy or radiation therapy
- •Age 18-70 years (female and male)
- •Eastern Cooperative Oncology Group ≤ 2
- •Surgical resectability
- •Neutrophils> 2.000/µl
- •Platelets > 100.000/µl
- •Normal value of Serum Creatinin
- •Albumin level > 29 г/л
- •Aspartate transaminase (AST) or alanine transaminase (ALT) less than 3 times the upper limits of normal (ULN)
- •Total Bilirubin less than 1.5 times the ULN
- •Written informed consent.
排除标准
- •Previous cytostatic chemotherapy or radiation therapy
- •Distant metastases or all primarily not resectable stages
- •Cancer relapse
- •Complicated gastric cancer (perforation, bleeding, sub or decompensated stenosis, dysphagia IV)
- •Diarrhea ≥ 2 according to the criteria of Common Terminology Criteria for Adverse Events (CTCAE) version 4.1;
- •Hypersensitivity against 5- Fluorouracil, Leucovorin, Oxaliplatin, Epirubicin and Docetaxel
- •Existence of contraindications against 5- Fluorouracil, Leucovorin, Oxaliplatin, Irinotecan or Docetaxel
- •Active coronary heart disease, Cardiomyopathy or cardiac insufficiency stage III-IV according to New York Heart Association (NYHA)
- •Severe non-surgical accompanying disease or acute infection (uncontrolled arterial hypertension, diabetes mellitus, stroke less than 6 months old, mental disorders, other tumors and others)
- •Malignant secondary disease, dated back < 5 years (exception: In-situ-carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)
- •Peripheral polyneuropathy > Grad II
- •Liver dysfunction (AST)/ALT>3,0xULN, ALT>3xULN, Bilirubin>1,5xULN)
- •Serum Creatinin >1,0xULN
- •Chronic inflammable gastro-intestinal disease
- •Inclusion in another clinical trial
- •Pregnancy or lactation
- •Hepatitis B or C in the active stage
- •Human immunodeficiency virus(HIV) infected
- •Serious concomitant somatic and mental illnesses / deviations or territorial causes that may prevent the patient from participating in the protocol and observing the protocol schedule
- •Foreigners or persons with limited legal status
研究组 & 干预措施
FOLFIRINOX
Irinotecan 180mg/m2 d1, d1-2 5-FU 2450 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
干预措施: Irinotecan (Drug)
FOLFIRINOX
Irinotecan 180mg/m2 d1, d1-2 5-FU 2450 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
干预措施: 5-FU (Drug)
FOLFIRINOX
Irinotecan 180mg/m2 d1, d1-2 5-FU 2450 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
干预措施: Leucovorin (Drug)
FOLFIRINOX
Irinotecan 180mg/m2 d1, d1-2 5-FU 2450 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
干预措施: Oxaliplatin (Drug)
FLOT
d1 Docetaxel 50mg/m2, d1-2 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m² every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
干预措施: 5-FU (Drug)
FLOT
d1 Docetaxel 50mg/m2, d1-2 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m² every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
干预措施: Leucovorin (Drug)
FLOT
d1 Docetaxel 50mg/m2, d1-2 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m² every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
干预措施: Oxaliplatin (Drug)
FLOT
d1 Docetaxel 50mg/m2, d1-2 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m² every two weeks (q2w) 4 cycles (4-8 weeks) pre-OP and 4 cycles (6-12 weeks) post-OP
干预措施: Docetaxel (Drug)
结局指标
主要结局
median overall survival
时间窗: 2 years
次要结局
- Pathologic complete response rate(1 month after surgery)
- Disease free survival(2 years)
- Perioperative Morbidity and Mortality(1 months after surgery)
- R0-Resection rate(1 month after surgery)