Fluorouracil, Oxaliplatin, and Leucovorin in Treating Patients With Metastatic Stomach Cancer or Gastroesophageal Junction Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving fluorouracil together with oxaliplatin and leucovorin works in treating patients with metastatic stomach cancer or gastroesophageal junction cancer.

Detailed Description
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OBJECTIVES: Primary Compare the response rate in patients with good risk genotype (TSER*2/*2 or TSER*2/*3 genotype [low TS expression]) to historical control response rates in non-genotype selected patients. OUTLINE: This is a multicenter study. Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on days 1 and 15. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression. Available tumor tissue samples are assessed for expression of TS at the mRNA and protein levels. The results are correlated with germline and tumor TSER genotypes as well as response to the study treatment regimen. Polymorphisms in other genes associated with treatment outcome or toxicity are also assessed. After completion of study treatment, patients are followed periodically for 4 years.

Official Title
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Pharmacogenomically Selected Treatment for Gastric and Gastroesophageal Junction (GEJ) Tumors: A Phase II Study

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin
* Genetic: gene expression analysis
* Genetic: polymorphism analysis
* Genetic: protein expression analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction Metastatic disease Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan No known active brain metastases Patients with treated brain metastases are eligible if stable off steroids for at least 30 days PATIENT CHARACTERISTICS: ECOG performance status ≤ 2 (Karnofsky performance status ≥ 60%) Life expectancy ≥ 3 months WBC ≥ 3,000/μL Absolute neutrophil count ≥ 1,500/μL Platelets ≥ 100,000/μL Total bilirubin ≤ 1.5 x upper limit of normal (ULN) AST or ALT ≤ 2.5 x ULN (< 5 x ULN if known liver metastases) Creatinine clearance ≤ 1.5 x ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 21 days after completion of study treatment No history of allergic reactions to fluorouracil or oxaliplatin No concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements PRIOR CONCURRENT THERAPY: No prior therapy for metastatic disease Prior neoadjuvant or adjuvant therapy is allowed if the disease-free interval has been longer than 6 months No other concurrent chemotherapy No concurrent combination anti-retroviral therapy for HIV-positive patients No concurrent routine prophylaxis with filgrastim (G-CSF) No other concurrent antineoplastic agents, including chemotherapy, radiation therapy, or biologic agents

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br> | Drug: fluorouracil<br>* Given through a vein over 5 minutes and then continuously over 46 hours on days 1 and 15.<br>Drug: leucovorin calcium<br>* through a vein over 2 hours on days 1 and 15.<br>Drug: oxaliplatin<br>* 500 ml D5W through a vein over 2 hours on days 1 and 15.<br>Genetic: gene expression analysis<br>* Blood collection<br>Genetic: polymorphism analysis<br>* Blood collection<br>Genetic: protein expression analysis<br>* Blood collection<br>Other: pharmacological study<br>* Blood collection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Each Response in Good Risk Genotype (Thymidylate Synthase Promoter Enhancer Region [TSER]*2/*2 or TSER*2/*3 Genotype [Low TS Expression]) | Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions. This is a one-time assessment. | every 8 weeks to progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the stomach, stage IV gastric cancer, recurrent gastric cancer