Inclusion Criteria:

• Histologic or cytologic proof of pancreatic adenocarcinoma.
• Subjects with biopsy-proven adenocarcinoma of the pancreas which is potentially resectable by preoperative imaging. Subjects will be considered potentially resectable using criteria defined by Pisters (Pisters et al., 2001):
• if imaging detects no evidence of extrapancreatic disease;
• no evidence of tumor extension to the superior mesenteric artery (SMA) or celiac axis (intact fat plane between the tumor and the adjacent visceral artery),
• patent superior mesenteric-portal vein confluence
• no encasement of portal or superior mesenteric vein.
• Karnofsky performance status ≥ 80.
• No active second malignancy except for basal cell carcinoma of the skin
• Normal renal, hepatic, and hematologic function at the time of enrollment as evidenced by:
• Serum creatinine level ≤1.6 mg/dl ( Calculated Creat clearance >50)
• Serum total bilirubin level ≤1.5 X ULN
• Urine protein excretion ≤ 1+ by urine dipstick
• White blood cell count ≥ 3.5x109/ml per ml and platelet count ≥ 100x109 per ml
• Age >18 years.
• Children are excluded because of toxic effects of bevacizumab and gemcitabine on growth and development during preclinical studies.
• For subjects with obstructive jaundice, the biliary tract must be drained with a temporary plastic or a short permanent metallic biliary stent.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Disease-Specific Exclusions
• Subjects who have received chemotherapy within 12 months prior to study entry.
• Prior use of radiotherapy or investigational agents for pancreatic cancer.
• Subjects who have undergone laparotomy for pancreas cancer within 6 weeks
• Any evidence of metastasis to distant organs (liver, lung, peritoneum).

• Symptomatic or endoscopic evidence of gastric outlet obstruction

  • Endoscopic findings suggesting tumor erosion into the gastrointestinal mucosa.

• Concurrent malignancies with evidence of active or measurable disease except basal cell carcinoma of the skin.
• General Medical Exclusions
• Inability to adhere to study and/or follow-up procedures
• History of allergic reactions or hypersensitivity to the study drugs (bevacizumab, gemcitabine, and proton pump inhibitors).
• Other concurrent experimental therapy.
• Because subjects with immune deficiency are at increased risk for lethal infections when treated with marrow-suppressive therapy, HIV-positive subjects receiving combination anti-retroviral therapy are excluded from the study.
• Bevacizumab-Specific Exclusions
• Subjects who have had recent surgery (prior 6 weeks)
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
• Subjects with the following co-morbid medical conditions:
• History of myocardial infarction or unstable angina within 12 months prior to study enrollment.
• Ascites
• Pregnancy/lactation - The effects of the study drugs on the developing human fetus are unknown. For this reason and because bevacizumab, gemcitabine, and radiation therapy used in this trial are known to be teratogenic in animal studies, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of study entry until 6 months after the completion of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A serum pregnancy test for those females of childbearing potential must be done prior to their receiving study drugs. Due to the combined effects of chemotherapy and radiation, breastfeeding is not allowed for 6 months after the completion of study participation.
• Regular aspirin use > 325 mg per day
• Regular NSAID use
• Bleeding diathesis, coagulopathy, need for full-dose anticoagulation or INR > 1.5
• Known central nervous system metastasis
• Previous cerebrovascular accident, transient ischemic attack, or seizure (within 6 months)
• Serious non-healing wound, ulcer, or bone fracture
• History of abdominal fistula, gastrointestinal perforation, diverticulitis, or intra-abdominal abscess within 6 months prior to study enrollment.
• Recent hemoptysis,
• Uncontrolled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) grade 2 or greater congestive heart failure (see Appendix I)
• Prior deep venous thrombosis or pulmonary embolism
• Urine protein excretion 2+ or ≥ 1 g per 24 hours
• Peripheral vascular disease such as lower extremity claudication and rest pain or prior lower extremity vascular surgery for arterial insufficiency
• Dyspnea requiring supplemental oxygen