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