Bevacizumab, Gemcitabine, and Oxaliplatin 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