RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether gemcitabine combined with R115777 is more effective than gemcitabine alone for pancreatic cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of gemcitabine with or without R115777 in treating patients who have advanced pancreatic cancer.

OBJECTIVES: I. Compare the overall survival of patients with advanced pancreatic cancer after treatment with gemcitabine with or without R115777. II. Compare quality of life in these patients with these treatment regimens. III. Compare objective response rate, progression free survival, and duration of objective response with these treatment regimens in these patients. IV. Estimate 6 month and 1 year survival rates in these patients after these treatment regimens. V. Assess the safety of these treatment regimens in these patients. VI. Determine the incidence of ras mutations in these patients with these treatment regimens.

PROTOCOL OUTLINE: This is a randomized, double blind, placebo controlled study. Patients are randomized to one of two treatment arms. Arm I: Patients receive R115777 orally every 12 hours in combination with gemcitabine IV over 30 minutes weekly for 7 weeks followed by 1 week of rest. Subsequent gemcitabine is given weekly for 3 weeks followed by 1 week of rest. Arm II: Patient receive gemcitabine as in arm I. Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed every 4 weeks on study, every 2 months in the first year, and then every 3 months for up to 5 years or until start of further treatment. Patients are followed every 2 months for the first year and then every 3 months for up to 5 years.

PROJECTED ACCRUAL: A total of 660 patients will be accrued for this study over 13.2 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Pathologically confirmed, locally advanced, unresectable or metastatic adenocarcinoma of the pancreas
• Measurable disease

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No other prior chemotherapy; At least 6 months since prior fluorouracil as a radiosensitizer
• Endocrine therapy: Not specified
• Radiotherapy: See Chemotherapy
• Surgery: See Disease Characteristics
• Other: No other systemic therapy for pancreatic cancer; At least 30 days since prior other investigational drugs; No concurrent proton pump inhibitors (e.g., omeprazole, lansoprazole, and pantoprazole)

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 2.0 mg/dL; Transaminase no greater than 5 times upper limit of normal
• Renal: Creatinine no greater than 1.5 mg/dL
• Cardiovascular: No uncontrolled or severe cardiovascular disease (e.g., myocardial infarction within past 6 months, congestive heart failure, unstable angina, clinically significant pericardial disease, or clinically significant arrhythmia)
• Other: No concurrent or prior malignancy within past 5 years except superficial basal cell carcinoma of the skin; No other concurrent disease that may preclude study; No known hypersensitivity to imidazole derivatives Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception
• For more information regarding this protocol, please call 1-888-773-9831. Approximately 90-100 United States and international centers are participating.