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

A Phase III, Randomized Study of Gemcitabine (Fixed-Dose Rate Infusion) and Oxaliplatin (NSC 266046) Versus Gemcitabine (Fixed-Dose Rate Infusion) Versus Gemcitabine (30-Minute Infusion) in Pancreatic Carcinoma

RATIONALE: Drugs used in chemotherapy such as gemcitabine and oxaliplatin use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them in different ways may kill more tumor cells. It is not yet known whether gemcitabine is more effective with or without oxaliplatin in treating pancreatic cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of gemcitabine with or without oxaliplatin in treating patients who have 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