Postoperative Chemotherapy With or Without Bevacizumab for Patients With Stage II or III Rectal Cancer

PRIMARY OBJECTIVES: I. Compare the overall survival of patients who have undergone prior surgery and neoadjuvant chemoradiotherapy for clinical stage II or III rectal cancer treated with adjuvant oxaliplatin, leucovorin calcium, fluorouracil with vs without bevacizumab. SECONDARY OBJECTIVES: I. Evaluate tolerance of treatment, patterns of failure, and disease-free survival in patients treated with these regimens EXPLORATORY OBJECTIVES: I. Assess long-term rectal function using the Patient Bowel Function/Uniscale questionnaire and the Functional Assessment of Cancer (FACT)-Diarrhea subscale in patients treated with these regimens. II. Validate the FACT-Diarrhea subscale. III. Assess long-term symptoms of oxaliplatin-related neurotoxicity using the FACT/Gynecologic Oncology Group (GOG)-Neurotoxicity subscale in patients treated with these regimens. IV. Correlate TS, DPD and TP expression (key targets for fluorouracil); retention of chromosome 18q alleles and microsatellite instability (MSI) with TGFβ1RII mutation (markers for fluorouracil efficacy); ERCC1, ERCC2, and XPF expression (participants in repair of adducts from oxaliplatin); and p53 gene mutation and possibly other molecular markers pertinent to vascular endothelial growth factor in tumor tissue specimens with treatment efficacy in these patients. V. Correlate tumor molecular prognostic markers (chromosome 18q allelic loss and MSI) with survival in patients treated with this regimen. OUTLINE: This is a randomized study. Patients are stratified according to Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1), clinical staging (high risk \[T3, N+, M0 or T4, any N, M0\] vs low risk \[T1-2, N+, M0 or T3, N0, M0\]), prior pre-operative oxaliplatin (yes vs no), and prior radiotherapy dose (40-50 Gy vs \> 50-55.8 Gy). Patients are randomized to 1 of 2 treatment arms in a 1:1 ratio. ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses\* in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive bevacizumab\*\* IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I\*. \[Note: \*Patients who received prior neoadjuvant oxaliplatin including patients on protocol NSABP-R-04 receive up to 9 courses of treatment followed by leucovorin calcium IV and fluorouracil IV with (arm II) or without (arm I) bevacizumab for up to 3 courses.\] \[Note: \*\*Patients no longer receive bevacizumab as of 4/29/2009 when accrual was terminated due to slow accrual for the study)\] Patients complete 10-15 minute questionnaires about bowel function at randomization, end of treatment, 12 months post-treatment and then annually to 5 years post-treatment. After completion of study treatment, patients are followed periodically for approximately 10 years. PROJECTED ACCRUAL: 2100 patients