• Overall survival (OS) [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: No ]
• Response rate in the subset of patients with measurable disease by RECIST [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: No ]
• CA19-9 response rate in the subset of patients with elevated baseline values [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: No ]
• Time to progression [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: No ]
• Safety and tolerability [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: Yes ]
• Quality of Life and pain control assessments [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: No ]
• Evaluation of pharmacodynamic parameters, including analysis of tumor tissue, if available, for EGFR expression and for exploratory markers of tumor progression or response to therapy [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: No ]

Eligible patients with pancreatic cancer will be treated with dual agent monoclonal antibody consisting of cetuximab and bevacizumab alone or in combination with gemcitabine

• Biological: Cetuximab
• Biological: Bevacizumab
• Drug: Gemcitabine

• Active Comparator: Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab,bevacizumab, and gemcitabine . On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
• Active Comparator: Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Inclusion Criteria:

• The patient has provided signed written informed consent.
• The patient is ≥18 years of age.
• The patient has histologically or cytologically-confirmed pancreatic adenocarcinoma not amenable to curative treatment with surgery or has documented or suspected extrapancreatic metastases.
• The patient has either (a) measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (see Section 11.3) or (b) non-measurable disease with an elevated baseline CA19-9 level (≥2 x the upper limit of normal [ULN]).
• The patient's ECOG performance status is ≤2.
• The patient has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥1500/mm3 and a platelet count ≥100,000/mm3 obtained within 2 weeks prior to the first dose of study medication.
• The patient has adequate hepatic function as defined by a total bilirubin ≤2.0 mg/dL and transaminases ≤5.0 x ULN obtained within 2 weeks prior to the first dose of study medication.
• The patient has adequate renal function as defined by serum creatinine ≤2.0 x ULN and urine dipstick for proteinuria ≤1+ obtained within 2 weeks prior to the first dose of study medication. If urine dipstick is ≥2+, then a 24-hour urine for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study. Urinalysis is also acceptable.

• If the patient is on full-dose anticoagulation therapy (eg, warfarin or low molecular weight [LMW] heparin), the following criteria must be met:

  • The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or be on a stable dose of LMW heparin
  • The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)

• If the patient is not on full-dose anticoagulation therapy, the following criteria must be met:

  • The patient has adequate coagulation function as defined by INR ≤1.5
  • The patient has a PTT ≤ULN obtained within 2 weeks prior to the first dose of study medication
• If a woman, the patient agrees to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study. If a male and sexually active, the patient agrees to use effective contraception.
• The patient is accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center.

Exclusion Criteria:

• Endocrine tumors or lymphoma of the pancreas
• Known brain metastases
• Prior therapy with an EGFR inhibitor or VEGF inhibitor
• Prior chemotherapy, hormonal therapy, or radiation therapy for advanced pancreatic cancer, patients who received chemotherapy and/or radiation therapy in the adjuvant setting will be eligible as long as the adjuvant therapy was completed >6 months prior
• Concurrent malignancy other than non-melanomatous skin cancer or carcinoma in situ of the cervix
• Concurrent treatment with other anti-cancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy
• Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
• History of arterial thrombotic events within 9 months
• History of uncontrolled hypertension (>150/100 mmHg) not on a stable regimen of anti-hypertensive therapy
• History of significant bleeding events or upper or lower gastrointestinal bleeding within 9 months
• History of gastrointestinal perforation within 12 months
• Serious non-healing wound ulcer, bone fracture, or major surgical procedure with 28 days
• If a woman, is pregnant or lactating
• An employee of the investigator or study center as well as family members of the employees