Gemcitabine With or Without Exatecan Mesylate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

OBJECTIVES:

• Compare the overall survival of patients with chemotherapy-naive locally advanced or metastatic cancer of the exocrine pancreas treated with exatecan mesylate and gemcitabine versus gemcitabine alone.
• Compare the measures of clinical benefit in patients treated with these regimens.
• Compare the anti-tumor efficacy of these regimens in this patient population.
• Determine the safety profile of exatecan mesylate and gemcitabine in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to performance status (60% vs 70-80% vs 90-100%), extent of disease (locally advanced vs metastatic), and prior radiotherapy for pancreatic cancer (yes or no). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive exatecan mesylate (DX-8951f) IV over 30 minutes immediately followed by gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive gemcitabine IV over 30 minutes once weekly for up to 7 weeks followed by one week of rest (course 1). For all subsequent courses, patients receive gemcitabine once weekly for 3 weeks followed by one week of rest. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly.

PROJECTED ACCRUAL: Approximately 340 patients (170 per treatment arm) will be accrued for this study within 18 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed epithelial cancer of the exocrine pancreas

• Locally advanced (unresectable) or metastatic disease
• No islet cell tumor, lymphoma, or sarcoma of the pancreas
• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

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 1.5 times upper limit of normal (ULN)
• AST no greater than 5 times ULN
• Albumin at least 2.8 g/dL

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No active congestive heart failure
• No uncontrolled angina
• No myocardial infarction

Other:

• No serious infection or life-threatening illness unrelated to tumor
• No other malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No overt psychosis or incompetency that would preclude study
• No history of a positive serology for HIV
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior systemic anticancer immunotherapy for pancreatic cancer
• No concurrent anticancer immunotherapy or other biologic therapy

Chemotherapy:

• No prior systemic anticancer chemotherapy for pancreatic cancer
• Prior fluorouracil as a radiosensitizer allowed
• No prior gemcitabine as a radiosensitizer
• No other concurrent anticancer chemotherapy

Endocrine therapy:

• Concurrent megestrol for appetite stimulation allowed

Radiotherapy:

• At least 28 days since prior radiotherapy and recovered
• No prior radiotherapy to more than 25% of estimated bone marrow reserve
• No concurrent anticancer radiotherapy

Surgery:

• At least 28 days since prior major surgery and recovered
• No concurrent surgery for cancer

Other:

• No prior investigational or other systemic anticancer therapy for pancreatic cancer
• No other concurrent investigational drugs