Bevacizumab and Gemcitabine Combined With Either Cetuximab or Erlotinib in Treating Patients With Advanced Pancreatic Cancer

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