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

OBJECTIVES:

• Compare survival of patients with locally advanced or metastatic pancreatic cancer treated with prolonged infusion gemcitabine with vs without oxaliplatin vs standard infusion gemcitabine.
• Compare the toxicity of these regimens in these patients.
• Compare the objective response in patients treated with these regimens.
• Compare the patterns of failure and progression-free survival of patients treated with these regimens.
• Compare the reported frequency of deep vein thrombosis and pulmonary embolism among patients treated with these regimens.
• Compare the changes in quality of life, including improved symptom control and/or additional side effects of patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0 or 1 vs 2) and disease stage (locally advanced vs metastatic). Patients are randomized to 1 of 3 treatment arms.

• Arm I (standard treatment): Patients receive gemcitabine IV over 30 minutes once weekly for 7 weeks followed by 1 week of rest for course 1 only. In all subsequent courses, patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15, with courses repeating every 4 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive gemcitabine IV over 150 minutes on days 1, 8, and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
• Arm III: Patients receive gemcitabine IV over 100 minutes on day 1 and oxaliplatin IV over 120 minutes on day 2. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then at 8 and 16 weeks.

Patients are followed for 3 years.

PROJECTED ACCRUAL: A total of 789 patients (263 per treatment arm) will be accrued for this study within 18 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinoma or poorly differentiated carcinoma
• Ineligible for curative resection
• Measurable and/or nonmeasurable disease
• Must have evidence of disease outside prior radiation fields OR radiologically confirmed progression of disease within the radiation fields after completion of radiotherapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,500/mm^3 OR
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 125,000/mm^3

Hepatic

• Bilirubin < 2.0 mg/dL
• AST < 3 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No uncontrolled cardiac disease

Other

• Not pregnant or nursing
• Negative pregnancy test

• Negative vaginal ultrasound for patients with an elevated beta human chorionic gonadotropin level
• Fertile patients must use effective nonhormonal contraception
• No other malignancies within the past 5 years except nonmetastatic, nonmelanoma skin cancer, carcinoma in situ of the cervix, or cancer cured by surgery or small field radiotherapy
• No active or uncontrolled infection
• No other active illness that would preclude study participation
• No symptomatic sensory peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for metastatic disease
• No prior (including adjuvant) gemcitabine or oxaliplatin
• Prior adjuvant chemotherapy allowed provided there was more than 6 months between the last dose of adjuvant chemotherapy and recurrence of pancreatic cancer
• Prior chemotherapy as a radiosensitizing agent allowed* NOTE: *To the primary site

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy to the primary tumor site and recovered
• No prior radiotherapy to more than 25% of the functional bone marrow

Surgery

• See Disease Characteristics
• Prior surgical resection allowed

Other

• No concurrent participation in supportive care trials
• Concurrent enrollment on protocol ECOG-E1Y03 allowed