5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) Versus Epirubicin, Cisplatin and 5-FU (ECF) in Patients With Locally Advanced, Resectable Gastric Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: 5-Fluorouracil
* Drug: Leucovorin
* Drug: Oxaliplatin
* Drug: Docetaxel
* Drug: Epirubicin
* Drug: Cisplatin
* Drug: 5-fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) ECOG ≤ 2 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 Exclusion Criteria: distant metastases or infiltration of adjacent structures or organs and all primarily not resectable stages relapse 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FLOT<br>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 | Drug: 5-Fluorouracil<br>* 2600 mg/m²d1 i.v. every 2 weeks<br>Drug: Leucovorin<br>* 200 mg/m², d1, i.v., every 2 weeks<br>Drug: Oxaliplatin<br>* 85 mg/m², d1, i.v., every 2 weeks<br>Drug: Docetaxel<br>* 50mg/m2, d1, i.v., every 2 weeks<br>|
| Active Comparator: ECF<br>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 | Drug: Epirubicin<br>* 50 mg/m2, d1, i.v., every 3 weeks<br>Drug: Cisplatin<br>* 60 mg/m², d1, i.v., every 3 weeks<br>Drug: 5-fluorouracil<br>* 200 mg/m², d1-d21, i.v., every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| median overall survival |  | 2 years follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| histopathological regression rate |  | 6 weeks after surgery | 
| disease free survival (DFS) |  | 2 years follow-up | 
| correlation of pCR and DFS with survival |  | 2 years follow-up | 
| Perioperative Morbidity and Mortality |  | up to 2 months after surgery | 
| R0-Resection rate |  | 2 months after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FLOT, gastric cancer, perioperative, ECF, pathological complete remission, locally advanced resectable adenocarcinoma of the esophagogastric juction or the stomach