The primary purpose of this trial is to define the maximum tolerated and/or recommended phase II dose of the combination of Avastin and Tarceva in patients undergoing radiation therapy for carcinoma of the pancreas. An additional primary objective is to describe the frequency and nature of grade III/IV and grade I/II toxicities associated with this regimen. Secondary objectives include describing 1-year disease-free survival and overall survival rates as well as to estimate clinical and pathologic complete response rates associated with this regimen.

This is a phase I/II study in which up to 18 patients will be enrolled in the phase I portion and up to an additional 26 patients in the phase II portion. Patients will be treated with Tarceva (cohort specified dose), along with fixed doses of Avastin and radiation therapy.

Avastin will be given as an IV dose on days 1, 15, and 29. Tarceva will be given as a once daily by mouth. On radiation days Tarceva will be taken immediately before or after XRT.

XRT will be given to a total dose of 50.4 Gy in 28 fractions, each fraction given once daily on Monday through Friday for 5.5 weeks

Inclusion Criteria:

• Age > 18 years
• Histologically and/or cytologically confirmed adenocarcinoma of the pancreas, T1-4, N0-1, M0. Patients should have disease for which combined modality therapy is indicated.
• Performance status 0-2
• Life expectancy > 3 months
• Adequate hematologic, renal, hepatic function
• Calculated creatinine Cl > 50 mL/min
• Use of effective means of contraception in patients of child-bearing potential.

Exclusion Criteria:

• No prior therapy for pancreatic cancer
• Previous treatment with bevacizumab or erlotinib
• Evidence of duodenal invasion or gastric outlet obstruction
• Presence of bleeding diathesis or coagulopathy
• History or prior arterial thrombotic event
• Conditions leading to inadequate gastrointestinal tract absorption
• Poorly controlled diarrhea .
• Presence of baseline proteinuria or renal dysfunction (CrCl < 50 (Cockcroft-Gault equation)
• Inadequately controlled hypertension
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• Clinically significant peripheral vascular disease
• Presence of central nervous system or brain metastases
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
• Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0
• Pregnant or lactating females
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
• Serious, non-healing wound, ulcer, or bone fracture
• Inability to comply with study and/or follow-up procedures
• Treatment for other carcinomas within the last five years, except cured non-melanoma skin cancer, curatively treated in-situ cervical cancer, or localized prostate cancer with a current PSA of <1.0 mg/dL on 2 successive evaluations, at least 3 months apart, with the most recent evaluation no more than 4 weeks prior to entry.
• Comorbid conditions that would complicate safety or compliance