RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of pancreatic cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with gemcitabine and oxaliplatin may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with gemcitabine and oxaliplatin works in treating patients with metastatic pancreatic cancer.

OBJECTIVES:

Primary

• Determine the 6-month survival of patients with metastatic adenocarcinoma of the pancreas treated with bevacizumab, gemcitabine, and oxaliplatin.

Secondary

• Determine the objective response rate in patients with measurable disease treated with this regimen.
• Determine median survival, progression-free survival, time to treatment failure, and overall survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine IV over 100 minutes and bevacizumab IV over 30-90 minutes on days 1 and 15. Patients also receive oxaliplatin IV over 120 minutes on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 courses of therapy beyond CR.

After completion of study treatment, patients are followed every 3-6 months for up to 5 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed ductal cell or undifferentiated adenocarcinoma of the pancreas

  • Previously untreated metastatic disease

• No islet cell or acinar cell carcinoma or cystadenocarcinoma

• No invasion of adjacent organs (i.e., duodenum or stomach) or major blood vessels ( i.e., superior mesenteric artery or celiac artery)

• No CNS metastasis

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10.0 g/dL
• No bleeding diathesis or uncontrolled coagulopathy
• No bleeding events within the past 6 months

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN) (stenting allowed)
• AST ≤ 5 times ULN
• No esophageal varices

Renal

• Creatinine ≤ 2 times ULN
• Proteinuria < 1+ by dipstick or urinalysis OR
• Protein < 1 g/24-hr urine collection
• No nephrotic syndrome

Cardiovascular

• No New York Heart Association class II-IV congestive heart failure
• No symptomatic, unstable angina, or coronary artery disease
• No uncontrolled cardiac arrhythmias
• No myocardial infarction within the past 6 months
• No uncontrolled hypertension
• No history of cerebrovascular events
• No clinically significant peripheral arterial disease
• No other clinically significant cardiac disease

Pulmonary

• No hemoptysis within the past 6 months

Immunologic

• No history of allergy or hypersensitivity to bevacizumab, oxaliplatin, or gemcitabine
• No hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No known allergy to other platinum compounds
• No ongoing or active infection

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment
• No serious, non-healing wound, ulcer, or bone fracture
• No pre-existing peripheral neuropathy > grade 1
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or prostate cancer with a Gleason score < 7
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No gastrointestinal bleeding within the past 6 months
• No unresolved physical trauma within the past 4 weeks

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 months since prior immunotherapy or biologic therapy
• No prior adjuvant bevacizumab
• No concurrent immunotherapy
• No concurrent colony-stimulating factors during the first course of study therapy

Chemotherapy

• Recovered from prior chemotherapy
• More than 4 months since prior adjuvant chemotherapy for completely resected disease
• At least 4 months since prior chemoradiotherapy for locally advanced disease
• More than 4 months since prior gemcitabine as a radiosensitizer or as maintenance therapy
• No prior cytotoxic chemotherapy for metastatic disease
• No prior adjuvant oxaliplatin
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Chemotherapy
• More than 4 months since prior radiotherapy
• No prior radiotherapy to > 25% of bone marrow
• No prior radiotherapy to sole site of measurable disease unless there is radiologically confirmed progression of the irradiated tumor
• No concurrent radiotherapy

Surgery

• More than 4 weeks since prior major surgery or trauma and recovered
• No concurrent surgery

Other

• More than 2 weeks since prior and no concurrent thrombolytic agents

  • Anticoagulation therapy with warfarin or low molecular weight heparin is allowed provided the following criteria are met:

    • At least 2 weeks at a stable dose
    • INR 2-3
    • No active bleeding or pathologic condition that confers a high risk of bleeding (e.g., tumor involving major vessels or known varices)

• No recent or concurrent participation in another study of experimental drugs