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.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the pancreas Drug Toxicity Pancreatic Cancer	Drug: fluorouracil  Drug: gemcitabine  Drug: triacetyluridine  Procedure: chemoprotection  Procedure: chemotherapy  Procedure: drug modulation  Procedure: high-dose chemotherapy  Procedure: supportive care/therapy	Phase III

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Alabama
      Brookwood Medical Center, Birmingham,  Alabama,  35209-6804,  United States; Recruiting
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294,  United States; Recruiting
California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Providence Saint Joseph Medical Center - Burbank, Burbank,  California,  91505,  United States; Recruiting
      Scripps Cancer Center at Scripps Clinic, La Jolla,  California,  92037,  United States; Recruiting
Florida
      Florida Cancer Institute, New Port Richey,  Florida,  34652,  United States; Recruiting
      Florida Cancer Specialists - World Plaza, Fort Myers,  Florida,  33908,  United States; Recruiting
      Florida Oncology Associates - South Side, Jacksonville,  Florida,  32207,  United States; Recruiting
      Memorial Cancer Institute at Memorial Regional Hospital, Hollywood,  Florida,  33021,  United States; Recruiting
      Northwest Oncology and Hematology Associates, Coral Springs,  Florida,  33065,  United States; Recruiting
      University of Miami Sylvester Comprehensive Cancer Center, Miami,  Florida,  33136,  United States; Recruiting
Georgia
      St. Joseph's Hospital, Savannah,  Georgia,  31419,  United States; Recruiting
Indiana
      Cancer Care Center, New Albany,  Indiana,  47150,  United States; Recruiting
Maryland
      Cancer Center at Greater Baltimore Medical Center, Baltimore,  Maryland,  21204-6881,  United States; Recruiting
      Wellstat Therapeutics, Gaithersburg,  Maryland,  20878,  United States; Recruiting
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
Missouri
      Capitol Comprehensive Cancer Care Clinic, Jefferson City,  Missouri,  65109,  United States; Recruiting
      David C. Pratt Cancer Center at St. John's Mercy, Saint Louis,  Missouri,  63141,  United States; Recruiting
New Mexico
      University of New Mexico Cancer Research and Treatment Center, Albuquerque,  New Mexico,  87131-5636,  United States; Recruiting
New York
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      Queens Medical Associates, PC, Fresh Meadows,  New York,  11365,  United States; Recruiting
Ohio
      Summit Oncology Associates, Akron,  Ohio,  44304,  United States; Recruiting
Pennsylvania
      Fox Chase - Temple Cancer Center, Philadelphia,  Pennsylvania,  19140,  United States; Recruiting
      Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey,  Pennsylvania,  17033-0850,  United States; Recruiting
South Carolina
      Cancer Centers of the Carolinas - Eastside, Greenville,  South Carolina,  29615,  United States; Recruiting
Texas
      Corpus Christi Cancer Center, Corpus Christi,  Texas,  78412,  United States; Recruiting
Canada, Ontario
      Ottawa Regional Cancer Centre at Ottawa Hospital - General Campus, Ottawa,  Ontario,  K1H 1C4,  Canada; Recruiting
      Regional Cancer Care at Thunder Bay Regional Health Sciences Centre, Thunder Bay,  Ontario,  P7B 6V4,  Canada; Recruiting
Canada, Quebec
      McGill Cancer Centre, Montreal,  Quebec,  H2W 1S6,  Canada; Recruiting

Study chairs or principal investigators

Lenny Smith, MS,  Study Chair,  Wellstat Therapeutics   

Study ID Numbers:  CDR0000068931; WELLSTAT-401.00.001; PRONEURON-401.00.001; UAB-0105; UAB-F010524008; NCT00024427
Record last reviewed:  November 2004
Last Updated:  April 4, 2005
Record first received:  September 13, 2001
ClinicalTrials.gov Identifier:  NCT00024427
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08