Perioperative Chemotherapy in Gastric Cancer

Study Overview
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Brief Summary
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Patients with resectable adenocarcinoma of the stomach or the esophagogastric 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 Oxaliplatin and Capecitabin (XELOX). Main objective of the study is histopathological regression rate.

Detailed Description
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284 рatients with resectable (T1b-4 and/or N-/+, M0) adenocarcinoma of the stomach or the esophagogastric junction without previous therapy will be included in this study. After laparocopic staging patients will be randomized to receive preoperatively 4 cycles FLOT or 4 cycles XELOX followed by surgery. Subsequently another 4 cycles of FLOT or 4 cycles XELOX are applicated. Primary endpoint is histopathological regression rate, secondary endpoints are disease-free survival, perioperative morbidity and mortality, correlation between pathological responce and disease-free survival.

Official Title
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Evaluation of Pathological Response in Patient With Resectable Gastric Cancer and Perioperative Chemotherapy FLOT Versus XELOX; Phase 2

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Oxaliplatin
* Drug: Leucovorin
* Drug: Fluorouracil
* Drug: Capecitabine
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: cT1b-T4b (cT4b - invasion in diaphragm, parenchyma of liver, spleen, pancreas, abdominal wall, small bowel, colon, distal part of splenic artery) cN0-3 M0 Age: 18 - 80 ECOG: 0 - 1 Histological type: adenocarcinoma Differentiation grade: G0 - G4 No previous surgery No previous chemotherapy No concomitant severe comorbidity Written informed consent Exclusion Criteria: cT1a, cT4b (invasion in truncus, hepatic artery, proximal part of splenic artery) Presense of distant metastases ECOG: 2 - 5 Age: <18 and >80 Severe concomitant comorbidity

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Active Comparator: XELOX<br>Oxaliplatin 130 mg/m2, d1 Capecitabine 1000 mg/m² two times per day (BID), d1-14, every 3 weeks (q3w) 4 cycles (12 weeks) pre-OP and 3 cycles (12 weeks) post-OP | Drug: Capecitabine<br>* 1000 mg/m² two times per day (BID), d1-14<br>Drug: Oxaliplatin<br>* 130 mg/m² d1 i.v. every 3 weeks<br>|
| 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: Docetaxel<br>* 50mg/m2, d1, i.v., every 2 weeks<br>Drug: Oxaliplatin<br>* 85 mg/m², d1, i.v., every 2 weeks<br>Drug: Leucovorin<br>* 200 mg/m², d1, i.v., every 2 weeks<br>Drug: Fluorouracil<br>* 2600 mg/m²d1 i.v. every 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histopathological regression rate (Becker regression criteria) | To determine histopathological regression rate after FLOT regimen compared to XELOX regimen in neoadjuvant settings | 2 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chemotherapy toxicity profile | To determine and compare toxicity profile in patients receiving XELOX or FLOT regimen | at the end of XELOX cycle (each cycle is 21 days) and FLOT cycle (each cycle is 14 days) | 
| Surgical complications rate | To determine surgical complication rate and profile after different types of regimens in neoadjuvant settings | up to 90th day after surgery | 
| 1-year disease-free survival rate | To determine the efficacy of FLOT regimen compared to XELOX regimen during the first year after the surgery | 1 year after surgery | 
| Correlation between histopathological regression and disease-free survival | To determine correlation between histopathological regression and disease-free survival in different chemotherapeutic settings | 2 years of follow-up after the last cycle of chemotherapy | 
| Median overall survival | To determine the efficacy of FLOT regimen compared to XELOX regimen by assessment of overall survival | 5 year follow up after the last cycle of chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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perioperative chemotherapy, pathological responce rate, gastrectomy