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

Phase III Randomized Study Of Gemcitabine Versus Gemcitabine-Oxaliplatine In Patients With Locally Advanced Or Metastatic Pancreatic Carcinoma

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether gemcitabine is more effective with or without oxaliplatin in treating pancreatic adenocarcinoma.

PURPOSE: This randomized phase III trial is studying gemcitabine and oxaliplatin to see how well they work compared to gemcitabine alone in treating patients with locally advanced or metastatic unresectable pancreatic adenocarcinoma.

OBJECTIVES:

Primary

• Compare the overall survival of patients with locally advanced or metastatic unresectable pancreatic adenocarcinoma treated with gemcitabine with or without oxaliplatin.

Secondary

• Compare the time of response in patients treated with these regimens.
• Compare the clinical benefit of and tolerance to these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.
• Compare the progression-free survival of patients treated with these regimens.

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

• Arm I: Patients receive gemcitabine IV over 30 minutes once weekly on weeks 1-7 and 9-11 in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive gemcitabine IV over 100 minutes on day 1 and oxaliplatin IV over 2 hours on day 2. Courses repeat every 14 days for up to 3 months in the absence of disease progression or unacceptable toxicity.

After the completion of chemotherapy, patients with locally advanced disease receive chemoradiotherapy.

Quality of life is assessed at baseline and then every 2 months.

PROJECTED ACCRUAL: A total of 230 patients (115 per treatment arm) will be accrued for this study within 24 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed pancreatic adenocarcinoma

  • Locally advanced or metastatic disease
  • Unresectable disease

• Measurable disease

  • At least 2 cm by a classical scanner and at least 1 cm by a spiral scanner

• No adenocarcinoma of the bile ducts or ampulla of Vater

• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 to 75

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic

• Bilirubin less than 1.5 times normal
• Alkaline phosphatase less than 5 times normal

Renal

• Creatinine less than 1.5 times normal
• No uncontrolled or persistent hypercalcemia

Cardiovascular

• No serious cardiac failure

Pulmonary

• No serious respiratory failure

Other

• Pain must be stabilized or controlled before initiation of study treatment
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other untreatable malignant tumor
• No serious psychological, familial, social, or geographical condition that would preclude study participation
• No neuropathy that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• No concurrent corticosteroids except for antiemetic therapy

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified