Combination Chemotherapy as First-Line Therapy in Treating Patients With Stage IV Gastric Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as floxuridine, leucovorin, oxaliplatin, and docetaxel, 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 combination chemotherapy works as first-line therapy in treating patients with stage IV gastric cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the overall response rate in patients with unresectable stage IV gastric adenocarcinoma treated with floxuridine, leucovorin calcium, oxaliplatin, and docetaxel as first-line treatment. Secondary Determine the feasibility of this regimen in managing patients with unresectable stage IV gastric adenocarcinoma who have not received prior chemotherapy for metastatic disease. Determine disease-free survival of patients treated with this regimen. Evaluate overall survival of patients treated with this regimen. Assess the safety and toxicity of this regimen in these patients. OUTLINE: Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and docetaxel IV over 30 minutes, floxuridine IV over 24 hours, and leucovorin calcium IV over 24 hours on days 1, 8, and 15. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 26 patients will be accrued for this study.

Official Title
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A Phase II Study of Weekly 24-hour Infusion 5-fluoro-deoxyuridine (FUdR)/Leucovorin With Oxaliplatin and Docetaxel (Taxotere) as First-line Treatment in Patients With Metastatic Gastric Adenocarcinoma (IIT# 14065)

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Floxuridine
* Drug: Leucovorin
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed gastric adenocarcinoma meeting the following criteria: Stage IV disease OR stage III disease that was re-staged as metastatic disease at time of surgery Unresectable disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan No CNS metastases PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100% Absolute neutrophil count ≥ 1,500/mm^3 Hemoglobin ≥ 8.0 g/dL Platelet count ≥ 100,000/mm^3 Bilirubin normal Creatinine ≤ 1.5 mg/dL Alkaline phosphatase (AP), AST, and ALT must meet 1 of the following criteria: AP normal AND AST and ALT ≤ 5 times upper limit of normal (ULN) AP ≤ 2.5 times ULN AND AST and ALT ≤ 1.5 times ULN AP ≤ 5 times ULN AND AST and ALT normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study therapy No peripheral neuropathy > grade 1 No history of severe hypersensitivity reaction to platinum agents (e.g., cisplatin or carboplatin), fluoropyrimidines, or drugs formulated with polysorbate 80 No concurrent serious illness that would preclude study treatment or compliance No active infections requiring intravenous antibiotic therapy No other malignancy within the past 5 years except for cervical carcinoma in situ, breast ductal carcinoma in situ, colonic polyp, or squamous cell or basal cell carcinoma of the skin No clinically significant uncontrolled cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease, or cardiac arrhythmias) or myocardial infarction within the past 12 months PRIOR CONCURRENT THERAPY: No prior radiotherapy for metastatic gastric carcinoma No prior chemotherapy for metastatic gastric carcinoma Prior neoadjuvant or adjuvant chemotherapy and/or radiotherapy allowed if completed therapy at least 12 months before study enrollment Chemotherapy may have included taxane, platinum, or fluoropyrimidine-based regimen At least 2 months since prior surgery and recovered No other concurrent investigational agents No other concurrent anticancer agents or therapies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FUdR + Leucovorin + Oxaliplatin + Docetaxel (Taxotere)<br>Treatment will be administered on an outpatient basis. Chemotherapy will be administered weekly, 3 out of 4 weeks, on days 1, 8 and 15: Day 1 and Day 15 Chemotherapy Administration: Patients will be administered oxaliplatin (85 mg/m2) and docetaxel (25 mg/m2) followed by FUdR/Leucovorin (110 mg/kg//500 mg/m2) on Day 1 and Day 15 of each cycle. Day 8 Chemotherapy Administration On Day 8, treatment will consist of docetaxel (25 mg/m2) followed by FUdR/Leucovorin (110mg/kg//500mg/m2). There will be no treatment delivered week 4 (Day 22). For the purpose of this study, one cycle equals four weeks. There will be a maximum of 6 cycles. | Drug: Docetaxel<br> <br> * Other names: Taxotere;Drug: Floxuridine<br> <br> * Other names: FudR;Drug: Leucovorin<br> <br> * Other names: Leucovorin calcium;Drug: Oxaliplatin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Achieving Clinical Response | Number of patients achieving complete response (CR) or partial response (PR) according to RECIST Criteria version 1.0. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Rate of Survival | Patients will be followed for overall survival from date of enrollment to date of death or last contact. The extent of follow up will be described by the range and median for deceased patients and for those alive at last follow up. We will estimate the 1 year survival rates by the Kaplan-Meier method. | 1 year | 
| Number of Participants Experiencing Adverse Events | Number of participants experiencing adverse events within 1 year of receiving combination therapy of FUDR + Leucovorin + Oxaliplatin + Docetaxel for metastatic gastric adenocarcinoma. | 1 year | 

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