The main purpose of this study is to test the safety and effectiveness of oxaliplatin, bevacizumab, and capecitabine given in combination with radiation therapy to see what effects (good or bad) they have on patients with biliary tract and gallbladder cancer.

There are two phases of study treatment. The first phase is for all patients and will last about 6 weeks. During this phase, oxaliplatin will be given intravenously once a week during weeks 1, 2, 4, and 5 on days 1, 8, 22, and 29; bevacizumab will be given intravenously once every 2 weeks during weeks 1, 3, and 5 on days 1, 15, and 29; capecitabine will be administered orally for 14 consecutive days (days 1-14), then a week of no capecitabine, followed by another 14 days of capecitabine (days 22-35).

Radiation therapy will be given once daily for 5 days (Monday-Friday) per week for a total of 28 treatments.

During this first phase of the study the following tests will be performed weekly: physical exam, vital signs, medical history, blood tests and urine tests.

After the first phase is finished patients will wait 4 weeks then have a CT scan, MRCP, blood tests and a physical exam to evaluate the status of the disease.

Phase two of the study is broken up into two groups: 1) patients who had tumors removed prior to entering study and 2) patients who entered the study with advanced disease.

If the patients had tumors removed prior to entering the study, they will be treated again with all 3 study drugs but no radiation over a 6-week period as they did earlier in the study. This 6-week regimen will be repeated twice for a total of 12 weeks of treatment.

Patients with advanced disease that could not be removed by surgery when they first entered the study but the evaluation tests after the first phase show the tumor has responded (reduced in size) and can now be resected, will have surgery to remove the tumors.

Following surgical recovery (8-10 weeks) they will be treated again with all 3 of the study drugs but no radiation over a 6-week period as they did earlier in the study. This 6-week regimen will be repeated twice for a total of 12 weeks of study treatment.

If the evaluation tests show that the patients' cancer has remained stable (not gotten worse or better) they will be treated again with all three study drugs but no radiation over a 6-week period as they did earlier in the study. This 6-week regimen will be repeated twice for a total of 12 weeks of study treatment.

During the additional 12 weeks of study treatment a physical exam, vital signs, medical history, blood testing and urine testing will be performed once every 3 weeks.

At the end of study treatment the following evaluations will be performed: physical exam, vital signs, blood work, CT scan of the chest and abdomen, MRCP, and tumor measurements by CT scans. These evaluations will be repeated every 3 months thereafter.

Patients will be removed from the study if their disease worsens or there are unacceptable side effects.

Inclusion Criteria:

• Histologically confirmed locally advanced unresectable biliary tract or gallbladder adenocarcinoma
• Patients with resected biliary tract or gallbladder adenocarcinoma who have residual tumor left will also be eligible.
• > 4 weeks since time of major surgery
• > 2 weeks since time of minor surgery
• > 4 weeks since time of major radiotherapy for other malignancy
• > 4 weeks since participation in any investigational drug study
• > 1 year since treatment for other carcinomas, except cured non-melanoma skin and treated in-situ cervical cancer
• 18 years of age or older
• ECOG performance status of 0-2
• Life expectancy > 12 weeks
• Absolute neutrophil count (ANC) > 1,500/mm3
• Hemoglobin > 9.0 gm/dl
• Platelets > 100,000/mm3
• SGOT < 5 x upper limits of normal (ULN)
• Total bilirubin < 2.5 mg/dl
• Creatinine clearance > 50 ml/min

Exclusion Criteria:

• Prior chemotherapy or radiation therapy for biliary tract or gallbladder cancer
• Peripheral neuropathy of grade 2 or greater
• Unstable angina
• Symptomatic congestive heart failure
• Myocardial infarction < 12 months prior to registration
• New York Heart Association classification III or IV
• Active or uncontrolled infection
• Known existing uncontrolled coagulopathy
• Malabsorption syndrome or lack of integrity of the upper gastrointestinal (GI) tract
• Prior unanticipated severe reaction to fluoropyrimidine therapy or known sensitivity to 5-fluorouracil, or known dihydropyrimidine dehydrogenase (DPD) deficiency
• Known brain metastases or carcinomatous meningitis
• Pregnant or lactating women
• Serious, non-healing wound, ulcer, or bone fracture
• Evidence of bleeding diathesis or coagulopathy