Triacetyluridine and Fluorouracil Compared With Gemcitabine in Treating Patients With Unresectable Locally Advanced, or Metastatic Pancreatic Cancer

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. Giving the drugs in different combinations may kill more tumor cells. Chemoprotective drugs such as triacetyluridine may protect normal cells from the side effects of chemotherapy. It is not yet known which chemotherapy regimen is more effective in treating pancreatic cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil plus triacetyluridine with that of gemcitabine in treating patients who have locally advanced or metastatic pancreatic cancer that cannot be treated with surgery.

Detailed Description
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OBJECTIVES: Compare the survival of patients with unresectable locally advanced or metastatic pancreatic cancer treated with triacetyluridine and high-dose fluorouracil vs gemcitabine. Compare the time to tumor progression, overall response rate, and response duration in patients treated with these regimens. Compare the safety of these regimens in these patients. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to disease stage (II or III vs IV). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive high-dose fluorouracil (5-FU) IV over 30 minutes once weekly on weeks 1-3 followed by 1 week of rest. After each dose of 5-FU, patients receive oral triacetyluridine every 8 hours for a total of 8 doses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive gemcitabine IV over 30 minutes once weekly on weeks 1-7 followed by 1 week of rest (course 1). Subsequent courses are given on weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed for survival. PROJECTED ACCRUAL: A total of 260 patients (130 per treatment arm) will be accrued for this study within 30 months.

Official Title
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An Open Label, Randomized, Controlled, Phase III, Multi-center, Clinical Trial Of PN401 With High Dose 5-Fluorouracil (5FU) Versus Gemcitabine For Treatment Of Patients With Advanced Pancreatic Cancer

Conditions
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Drug/Agent Toxicity by Tissue/Organ, Pancreatic Cancer

Intervention / Treatment
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* Drug: fluorouracil
* Drug: gemcitabine hydrochloride
* Drug: triacetyluridine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the pancreas Unresectable locally advanced or metastatic disease Stage II, III, or IV Measurable or evaluable disease No elevated tumor marker (CA 19-9) only No clinically significant third-space fluid accumulation (e.g., ascites or pleural effusion) No carcinoid, islet cell, or lymphoma of the pancreas No prior or concurrent brain or leptomeningeal metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life expectancy: At least 3 months Hematopoietic: WBC at least 3,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9.5 g/dL Hepatic: Bilirubin no greater than 2.0 mg/dL ALT or AST less than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present) No uncontrolled hepatic dysfunction Renal: Creatinine less than 2.0 mg/dL No uncontrolled renal dysfunction Cardiovascular: No uncontrolled cardiovascular disease requiring therapy, including the following: Angina Arrhythmias Uncompensated cardiac failure Myocardial infarction within the past 6 months Pulmonary: No uncontrolled pulmonary dysfunction Gastrointestinal: Able to take and/or retain oral medication No uncontrolled malabsorption syndrome or any other condition that would interfere with intestinal absorption Other: No known allergy to fluorouracil (5-FU), gemcitabine, triacetyluridine, or any of their components No dihydropyrimidine-dehydrogenase deficiency No active uncontrolled infection No uncontrolled neurologic or psychiatric dysfunction No other malignancy except previously resected basal cell cancer or curatively resected stage I or less cervical cancer that has been disease free for at least 5 years Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent biologic therapy (including immunotherapy) for cancer Chemotherapy: No prior chemotherapy for cancer other than as a radiosensitizer No prior 5-FU or gemcitabine other than as a radiosensitizer No prior triacetyluridine No other concurrent chemotherapy (including leucovorin calcium) for cancer Endocrine therapy: No concurrent hormonal therapy for cancer Concurrent megestrol, oral contraceptives, or postmenopausal estrogen replacement therapy allowed Radiotherapy: Prior radiotherapy allowed No concurrent radiotherapy Surgery: See Disease Characteristics Prior resection of pancreas allowed Other: At least 30 days since prior investigational drug or therapeutic device No other concurrent anticancer therapy No other concurrent investigational drugs or devices No concurrent drugs that would interact adversely with 5-FU or gemcitabine

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fluorouracil|High dose 5-FU|
|Drug: gemcitabine hydrochloride|Normal dose to treat pancreatic cancer|
|Drug: triacetyluridine|6 grams (12 tablets)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Open Label Randomized Phase 3 Multi-Center Trial of PN401 plus high dose 5-FU versus Gemcitabine in Advanced Pancreatic Cancer Patients |  | Disease progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug/agent toxicity by tissue/organ, stage II pancreatic cancer, stage III pancreatic cancer, recurrent pancreatic cancer, adenocarcinoma of the pancreas, stage IV pancreatic cancer