S9915 Triacetyluridine, Fluorouracil, and Leucovorin in Treating Patients With Unresectable, Locally Advanced, or Metastatic Cancer of the Esophagus or Stomach

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs such as triacetyluridine may protect normal cells from the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of triacetyluridine, fluorouracil, and leucovorin in treating patients who have unresectable, locally advanced, or metastatic cancer of the esophagus or stomach.

Detailed Description
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OBJECTIVES: Assess the 6-month survival rate in patients with unresectable, locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction treated with triacetyluridine, fluorouracil, and leucovorin calcium. Evaluate the qualitative and quantitative toxic effects of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 30 minutes beginning 1 hour into leucovorin calcium infusion on days 1, 8, 15, 22, 29, and 36. Patients receive oral triacetyluridine every 8 hours on days 1-3, 8-10, 15-17, 22-24, 29-31, and 36-38 beginning 8 hours after completion of each fluorouracil infusion. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for up to 3 years. PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.

Official Title
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A Phase II Study of PN-401, 5-FU and Leucovorin in Unresectable or Metastatic Adenocarcinoma of the Stomach

Conditions
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Esophageal Cancer, Gastric Cancer

Intervention / Treatment
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* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: triacetyluridine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically proven unresectable, locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction No known brain metastases Negative brain imaging required for neurologic signs and symptoms PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0-1 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count greater than 100,000/mm^3 Hepatic: Bilirubin no greater than upper limit of normal (ULN) SGOT or SGPT no greater than 1.5 times ULN (5 times ULN if liver tumor present) Renal: Creatinine no greater than ULN Other: Not pregnant or nursing Fertile patients must use effective contraception Must be able to swallow oral medication No AIDS syndrome or HIV-associated complex No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy No concurrent biologic therapy Chemotherapy: No prior chemotherapy for advanced or metastatic gastric cancer At least 6 months since prior chemotherapy as adjuvant or radiation sensitizer Endocrine therapy: Not specified Radiotherapy: At least 1 month since prior radiotherapy and recovered No concurrent radiotherapy Surgery: At least 3 weeks since prior major surgical resection of intra-abdominal organs and recovered

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: 5-FU, Leucovorin and PN-401<br>PN401 is given on Days 1-3 weekly for six weeks; 5FU and leucovorin are given on Day 1 weekely for six weeks; followed by two weeks of rest. Continued in 8 week cycles until one of the criteria for removal from treatment is met. | Drug: fluorouracil<br> <br> * Other names: 5-FU;Drug: leucovorin calcium<br> <br> * Other names: LCV; leucovorin;Drug: triacetyluridine<br> <br> * Other names: PN-401;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six month survival |  | six months after registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluate quantitative and qualitative toxicities |  | three years at most | 

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