Bevacizumab, Erlotinib and 5-Fluorouracil With External Beam Radiation Therapy in Locally Advanced Rectal Cancer

Inclusion Criteria:

* Histologically confirmed primary adenocarcinoma of the rectum that begins within 15cm of the anal verge as determined by sigmoidoscopy or colonoscopy
* Clinical T3 or T4 tumors as determined by endoscopic ultrasound and/or rectal MRI
* ECOG performance status of 0-2
* 18 years of age or older
* Creatinine of \< 2.0
* Adequate hepatic function
* Adequate hematopoietic function
* Use of effective means of contraception in subjects of child-bearing potential

Exclusion Criteria:

* Evidence of metastatic disease as determined by chest/abdominal/pelvic CT or physical exam
* Prior chemotherapy or radiation therapy for treatment of colorectal cancer
* Prior treatment with 5-FU
* Prior treatment with a tyrosine kinase inhibitor, EGFR inhibitor, or VEGF inhibitor
* Patients must not be receiving any other investigational agent
* Prior malignancy within the last 5 years except for completely excised skin cancer, in situ cervical cancer
* Warfarin anticoagulation
* Co-existent malignant disease
* Current or recent participation in a clinical trial (within 4 weeks from the first day of treatment)
* Pregnancy
* Blood pressure of \>150/100 mmHg
* Unstable angina
* NYHA Grade II or greater congestive heart failure
* History of myocardial infarction within 6 months
* History of stroke within 6 months
* Clinically significant peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy
* Presence of central nervous system or brain metastases
* Major surgical procedure, open biopsy, or significant trauma injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the course of the study
* Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0
* Pregnant or lactating
* Urine protein:creatinine ratio \> or equal to one at screening
* 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