FOLFIRINOX vs FLOT Chemotherapy for Resectable Gastric or Esophagogastric Junction Adenocarcinoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Fluoruracil, Stomach Neoplasms, Gastrointestinal Neoplasms, Docetaxel, Oxaliplatin, Irinotecan Hydrochloride

Intervention / Treatment
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* Drug: Irinotecan
* Drug: 5-FU
* Drug: Leucovorin
* Drug: Oxaliplatin
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: FOLFIRINOX<br>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 | Drug: Irinotecan<br>* d1 Irinotecan 180mg/m² every two weeks<br>Drug: 5-FU<br>* d1-2 5-FU 2450 mg/m² every two weeks<br>Drug: Leucovorin<br>* d1 Leucovorin 200 mg/m² every two weeks<br>Drug: Oxaliplatin<br>* d1 Oxaliplatin 85 mg/m² every two weeks<br>|
| Active Comparator: FLOT<br>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 | Drug: 5-FU<br>* d1-2 5-FU 2450 mg/m² every two weeks<br>Drug: Leucovorin<br>* d1 Leucovorin 200 mg/m² every two weeks<br>Drug: Oxaliplatin<br>* d1 Oxaliplatin 85 mg/m² every two weeks<br>Drug: Docetaxel<br>* d1 Docetaxel 50mg/m2 every two 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FLOT, gastric cancer, pathological complete, FOLFIRINOX, gastrectomy, adenocarcinoma of the esophagogastric junction, adenocarcinoma of the stomach