A Phase II Study of Bevacizumab With Concurrent Capecitabine and Radiation Followed by Maintenance Gemcitabine and Bevacizumab For Locally Advanced Pancreatic Cancer

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the pancreas

- Locally advanced disease

- Unresectable disease

- All malignant disease must be encompassable within a single irradiation field

- Radiographically assessable disease

- Patients with biliary or gastroduodenal obstruction are eligible provided drainage or
surgical bypass was performed prior to initiation of study treatment

- No evidence of gastric outlet obstruction

- No evidence of duodenal invasion on CT scan

- No evidence of metastatic disease in the major viscera

- No peritoneal seeding or ascites

- Performance status - Zubrod 0-1

- Granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- No evidence of bleeding diathesis

- ALT < 3 times upper limit of normal

- Bilirubin < 2.0 mg/dL

- INR ≤ 1.5

- No evidence of coagulopathy

- Creatinine clearance > 50 mL/min

- Urine protein < 1,000 mg by 24-hour urine collection (for patients with proteinuria ≥
1+ by dipstick or urinalysis OR urine protein:creatinine ratio ≥ 1.0)

- No myocardial infarction within the past 6 months

- No unstable angina within the past 6 months

- No arterial thromboembolic events within the past 6 months, including any of the
following:

- Transient ischemic attack

- Cerebrovascular accident

- Clinically significant peripheral artery disease

- No unstable symptomatic arrhythmia requiring medication (e.g., chronic atrial
arrhythmia [i.e., atrial fibrillation or paroxysmal supraventricular tachycardia])

- Patients with an atrial arrhythmia are eligible provided the condition is well
controlled on stable medication

- No New York Heart Association class II-IV congestive heart failure

- No history of arteriovenous malformation

- No history of aneurysm

- No uncontrolled hypertension (i.e., blood pressure > 160/90 mm Hg with medication)

- No other clinically significant cardiac disease

- No AIDS

- No significant infection

- No known hypersensitivity to Chinese hamster ovary cell products or other
recombinant human antibodies

- Not pregnant

- No nursing during and for ≥ 3-4 months after completion of study treatment

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 3-4 months after
completion of study treatment

- No history of gastrointestinal fistula or perforation

- No other malignancy within the past two years except nonmelanoma skin cancer or
carcinoma in situ of the cervix, uterus, or bladder

- No significant traumatic injury within the past 4 weeks

- No serious nonhealing wound or ulcer

- No current healing fracture

- No known or suspected dihydropyrimidine dehydrogenase deficiency

- No other medical condition that would preclude study participation

- No concurrent interleukin-11

- No prior chemotherapy for pancreatic cancer

- More than 2 years since prior chemotherapy for another malignancy

- No prior radiotherapy to the planned irradiation field

- No concurrent intensity modulated radiotherapy

- No other concurrent radiotherapy

- See Disease Characteristics

- More than 4 weeks since prior major surgical procedure or open biopsy

- More than 1 week since prior fine needle aspiration or core biopsy

- No prior organ transplantation

- No concurrent major surgical procedure

- More than 30 days since prior and no concurrent cimetidine

- Concurrent ranitidine or a drug from another anti-ulcer class allowed

- More than 4 weeks since prior and no concurrent sorivudine or brivudine

- No concurrent warfarin during chemoradiotherapy

- Concurrent warfarin allowed beginning 2 weeks after completion of
chemoradiotherapy

- Concurrent low molecular weight heparin allowed (at any time during study
participation)

- No other concurrent investigational agents

- No other concurrent cytotoxic agents