A Randomized Multicenter Phase II/III Study Comparing 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) Versus Epirubicin, Cisplatin and 5-FU (ECF) in Patients With Locally Advanced Resectable Adenocarcinoma of the Esophagogastreal Junction or the Stomach
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 716
- 试验地点
- 1
- 主要终点
- median overall survival
研究概览
简要总结
Patients with locally advanced resectable adenocarcinoma of the stomach or the esophagogastreal junction 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 Epirubicin, Cisplatin and 5-FU (ECF). Main objective of the study is median overall survival.
详细描述
714 Patients with locally advanced resectable (T2-4 and/or N+, M0) adenocarcinoma of the stomach or the esophagogastreal junction without previous therapy will be included in this study. After randomization patients receive perioperatively 4 cycles FLOT or 3 cycles ECF, followed by a restaging of the tumour status and surgery. Subsequently another 4 cycles of FLOT or 3 cycles ECF are applicated. Then a central validation of the pathological remission rate is scheduled. Primary endpoint is overall survival, secondary endpoints are disease free survival, perioperative morbidity and mortality, histopathologic regression rate and R0-resection rate.
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
- •locally advanced (>T1) and/or nodal positive (N+) histologically proven adenocarcinoma of the esophagogastreal junction (AEG I-III) or the stomach without distant metastases (M0) and without infiltration of adjacent structures and organs
- •no previous surgical resection
- •no previous cytostatic chemotherapy
- •Age > 18 years (female and male)
- •surgical resectability
- •Exclusion of peritoneal carcinomatosis (if clinically suspected) via laparoscopy
- •Leucocytes > 3.000/µl
- •Platelets > 100.000/µl
- •Serum creatinin ≤ 1.5x of normal value, or Creatinin-Clearance > 50 ml/min
- •written informed consent.
- •Ejection fraction > 50% in echocardiography before start of therapy
排除标准
- •distant metastases or infiltration of adjacent structures or organs and all primarily not resectable stages
- •Hypersensitivity against 5- Fluorouracil, Leucovorin, Oxaliplatin, Cisplatin. Epirubicin and Docetaxel
- •Existence of contraindications against 5- Fluorouracil, Leucovorin, Oxaliplatin, Cisplatin, Epirubicin or Docetaxel
- •Active CHD, Cardiomyopathy or cardiac insufficiency stage III-IV according to NYHA
- •malignant secondary disease, dated back < 5 years (exception: In-situ-carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)
- •severe non-surgical accompanying disease or acute infection
- •peripheral polyneuropathy > NCI Grad II
- •severe liver dysfunction (AST/ALT>3,5xULN, AP>6xULN, Bilirubin>1,5xULN)
- •chronic inflammable gastro-intestinal disease
- •inclusion in another clinical trial
- •pregnancy or lactation
研究组 & 干预措施
FLOT
Docetaxel 50mg/m2, d1 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (8 weeks) pre-OP and 4 cycles (8 weeks) post-OP
干预措施: Docetaxel (Drug)
FLOT
Docetaxel 50mg/m2, d1 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (8 weeks) pre-OP and 4 cycles (8 weeks) post-OP
干预措施: 5-fluorouracil (Drug)
FLOT
Docetaxel 50mg/m2, d1 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (8 weeks) pre-OP and 4 cycles (8 weeks) post-OP
干预措施: Leucovorin (Drug)
FLOT
Docetaxel 50mg/m2, d1 5-FU 2600 mg/m², d1 Leucovorin 200 mg/m², d1 Oxaliplatin 85 mg/m², d1 every two weeks (q2w) 4 cycles (8 weeks) pre-OP and 4 cycles (8 weeks) post-OP
干预措施: Oxaliplatin (Drug)
ECF
Epirubicin 50 mg/m2, d1 Cisplatin 60 mg/m², d1 5-FU 200 mg/m², d1-d21 every 3 weeks (q3w) 3 cycles (9 weeks) pre-OP and 3 cycles (9 weeks) post-OP
干预措施: Epirubicin (Drug)
ECF
Epirubicin 50 mg/m2, d1 Cisplatin 60 mg/m², d1 5-FU 200 mg/m², d1-d21 every 3 weeks (q3w) 3 cycles (9 weeks) pre-OP and 3 cycles (9 weeks) post-OP
干预措施: Cisplatin (Drug)
ECF
Epirubicin 50 mg/m2, d1 Cisplatin 60 mg/m², d1 5-FU 200 mg/m², d1-d21 every 3 weeks (q3w) 3 cycles (9 weeks) pre-OP and 3 cycles (9 weeks) post-OP
干预措施: 5-fluorouracil (Drug)
结局指标
主要结局
median overall survival
时间窗: 2 years follow-up
次要结局
- correlation of pCR and DFS with survival(2 years follow-up)
- histopathological regression rate(6 weeks after surgery)
- R0-Resection rate(2 months after surgery)
- disease free survival (DFS)(2 years follow-up)
- Perioperative Morbidity and Mortality(up to 2 months after surgery)
研究者
Prof. Dr. S.E. Al-Batran
Principal Investigator
Krankenhaus Nordwest