Phase II Trial of Bevacizumab, Gemcitabine, Oxaliplatin in Patients With Metastatic Pancreatic Adenocarcinoma

Inclusion Criteria

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