A Randomized Phase II Study of Bevacizumab (NSC# 704865) and Gemcitabine in Combination With Either Cetuximab (NSC# 714692) or OSI-774 (NSC# 718781) in Patients With Advanced Pancreatic Cancer

Study start date: July 1, 2004

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of the pancreas * Advanced disease * Patients with locally advanced disease must have disease that extends outside the boundaries of a standard radiation port * Not amenable to curative surgery or radiotherapy * Measurable disease * At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan * Pleural effusions and ascites are not considered measurable lesions * No CNS disease, including primary brain tumors or brain metastasis * No tumor invasion into the duodenum * Performance status - ECOG 0-2 * More than 3 months * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * WBC ≥ 3,000/mm\^3 * No history of bleeding diatheses * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * SGOT and SGPT ≤ 2.5 times ULN (5 times ULN if liver metastases are present) * INR ≤ 1.5 (≤ 3 for patients on warfarin) * No esophageal varices * Creatinine ≤ 1.5 mg/dL * Creatinine clearance ≥ 60 mL/min * Urine protein \< 1+ * 24-hour urine protein \< 500 mg * No history of a recent cerebrovascular accident * No clinically significant cardiovascular disease * No uncontrolled hypertension * No New York Heart Association class II-IV congestive heart failure * No serious cardiac arrhythmia requiring medication * No peripheral vascular disease ≥ grade II * None of the following arterial thromboembolic events within the past 6 months: * Transient ischemic attack * Cerebrovascular accident * Unstable angina * Myocardial infarction * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for at least 3 months after study participation * HIV negative * No significant traumatic injury within the past 28 days * No gastrointestinal tract disease resulting in an inability to take oral medication * No allergic reactions to compounds similar to bevacizumab, cetuximab, or erlotinib (e.g., Chinese hamster ovary cell products or recombinant humanized antibodies) * No serious or non-healing wound, ulcer, or bone fracture * No active infection requiring antibiotics * No other active malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * No prior bevacizumab or cetuximab * No other prior vascular endothelial growth factor inhibitors * No prior gemcitabine * No prior cytotoxic chemotherapy for metastatic disease * At least 4 weeks since prior adjuvant chemotherapy (6 weeks for mitomycin or nitrosoureas) * At least 4 weeks since prior radiotherapy * Must have a site of measurable disease outside the radiation port * No prior surgical procedure affecting absorption * More than 28 days since prior major surgical procedure or open biopsy * More than 7 days since prior core biopsy * No concurrent major surgical procedures * No prior erlotinib * No other prior epidermal growth factor receptor inhibitors * At least 30 days since prior investigational drugs * More than 1 month since prior thrombolytic agents * Concurrent warfarin or low molecular weight heparin allowed provided the following criteria are met: * Currently therapeutic on a stable dose * INR target range ≤ 3 * Patients undergo weekly INR testing * No evidence of active bleeding or pathological condition that carries high risk of bleeding (e.g., tumor invading adjacent organs or esophageal varices) * No concurrent chronic daily therapy with aspirin (\> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function * No other concurrent antiplatelet medications * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent anticancer therapies or agents * No other concurrent investigational drugs