5-Fluorouracil, Bevacizumab, and Radiation Followed by Modified FOLFOX6 and Bevacizumab in Stage II/III Rectal Cancer

All eligible patients will receive combined modality treatment initially. Systemic treatment will begin 4-6 weeks after completion of the Combined Modality portion and will complete 4 cycles of a 4 week regimen. Patients with no evidence of disease following systemic therapy may continue single agent bevacizumab for up to one year. After all treatment is completed, patients will be re-evaluated with imaging to establish a new baseline. Patients will be re-evaluated thereafter for up to a total of 5 years.

Combined Modality Treatment:

• bevacizumab 5mg/kg IV infusion days 1, 15, and 29
• fluorouracil 225mg/m2 IV continuous infusion days 1-42
• radiation 1.8 Gy/day or 28 fractions weeks 1-6

Systemic Treatment:

• 5-fluorouracil 400 mg/m2 bolus
• 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15
• leucovorin 350 mg prior to FU on days 1 and 15
• oxaliplatin 85 mg/m2 days 1 and 15
• bevacizumab 5 mg/kg days 1 and 15

Inclusion criteria

• Histologically confirmed Stage I or II rectal cancer
• Patients must be candidates for preoperative or adjuvant chemoradiation.
• Patients enrolling in the adjuvant chemoradiation cohort must have undergone surgical resection of the primary rectal tumor between 28 and 56 days (i.e., 4-8 weeks) prior to study treatment.
• ECOG performance status 0-1
• Adequate bone marrow, liver, and kidney function
• At least 18 years of age
• Able to give written informed consent

Exclusion criteria

• Treatment with prior chemotherapy or radiation for rectal cancer
• History of myocardial infarction
• Uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication or peripheral vascular disease
• History of stroke within 6 months
• History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess within 6 months
• Symptomatic sensory or peripheral neuropathy
• Prior treatment with anti-angiogenic agents
• Prior malignancy in the past 5 years
• Active infections or serious underlying medical condition
• Major surgery less than 28 days prior
• Women who are pregnant or lactating
• Thrombolytic therapy within 10 days of starting bevacizumab
• PEG tube, G-tube, or external biliary stents
• Proteinuria
• Non healing wound, ulcer or fracture
• History of bleeding diathesis or coagulopathy
• Hemoptysis
• Participation in another experimental trial within 28 days
• Uncontrolled anticoagulant therapy