Combination Chemotherapy With or Without Bevacizumab in Treating Patients Who Have Had Surgery for Stage II or Stage III Rectal Cancer (Groups I and II Closed to Accrual as of 4/29/2009)

Inclusion Criteria:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 3 months after study treatment
• No other previous or concurrent malignancy except nonmelanoma skin cancer, breast cancer in situ, carcinoma in situ of the cervix, or previously treated nonpelvic cancer that has been disease-free for > 5 years
• Patients with a history of breast cancer (without evidence of disease) who remain on hormonal therapy for > 5 years are eligible
• No active bleeding not related to the primary rectal tumor within the past 6 months
• No active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy
• No active gastroduodenal ulcer determined by endoscopy
• No serious or nonhealing wound, skin ulcer, or bone fracture
• No clinically significant peripheral sensory or motor neuropathy >= grade 2

• No nonmalignant systemic disease (e.g., cardiovascular, renal, or hepatic) that would preclude study treatment including, but not limited to, any of the following:

  • New York Heart Association class III or IV congestive heart failure
  • Concurrent symptomatic arrhythmia
• No transient ischemic attack or cerebrovascular accident
• No arterial thromboembolic event, unstable angina, or myocardial infarction within the past 12 months
• No significant peripheral vascular disease
• No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude study requirements
• Patients with a history of hypertension must have blood pressure < 150/90 mm Hg AND be on a stable regimen of antihypertensive therapy
• No significant traumatic injury within the past 28 days
• No known allergy to platinum compounds
• No other prior chemotherapy or pelvic radiotherapy except as neoadjuvant treatment for current diagnosis of rectal cancer

• No prior invasive procedure, including either of the following:

  • Major surgical procedure or open biopsy within the past 28 days
  • Core biopsy or other minor procedure, except placement of a vascular access device, within the past 7 days
• Concurrent participation on protocol NSABP-R-04 allowed

• Histologically confirmed adenocarcinoma of the rectum meeting 1 of the following clinical (e.g., before neoadjuvant therapy) or pathologic staging criteria:

  • T3, N+, M0
  • T3, N0, M0
  • T4, N0, M0
  • Any T, N1-2, M0

• T4, N0-2, M0 disease must meet 1 of the following criteria:

  • Clinically fixed tumor on rectal examination with tumor adherent to the pelvic sidewall or sacrum
  • Hydronephrosis on CT scan or IVP
  • Ureteric or bladder invasion as documented by cystoscopy and cytology or biopsy
  • Invasion into prostate
  • Vaginal or uterine involvement
• Must have undergone complete tumor resection >= 28 days ago and able to begin treatment by day 56
• No evidence of metastatic disease on the surgical/intraoperative examination
• Must have undergone concurrent neoadjuvant chemoradiotherapy*

• Must have undergone prior radiotherapy at 40-55.8 Gy** AND received 1 of the following chemotherapy regimens:

  • Continuous infusion of fluorouracil with or without oxaliplatin; fluorouracil and leucovorin calcium
  • Capecitabine with or without oxaliplatin; capecitabine with or without oxaliplatin OR a continuous infusion of fluorouracil with or without oxaliplatin received on protocol NSABP-R-04
• NOTE: *Neoadjuvant chemoradiotherapy received on protocol NSABP-R-04 allowed provided it met these criteria
• NOTE: **Intensity-modulated radiotherapy allowed
• No evidence of metastatic disease confirmed by CT scan, MRI, or ultrasound of the liver or chest CT scan or chest x-ray within the past 6 months
• No evidence of tumor outside of the pelvis, including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy
• ECOG performance status 0-1
• Platelet count >= 100,000/mm^3
• Absolute granulocyte count >= 1,500/mm^3
• Bilirubin normal (unless chronic grade 1 bilirubin elevation due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin)
• Alkaline phosphatase (AP) < 2.5 times upper limit of normal (ULN) and AST < 1.5 times ULN
• Hepatitis B and C negative (for patients with AP > normal) unless previously vaccinated
• Serum creatinine =< 1.5 times ULN
• Urine protein:creatinine (UPC) ratio < 1.0 OR urine protein < 1 g on 24-hour urine collection
• INR =< 1.5

• INR > 1.5 allowed provided patient is on full-dose anticoagulants AND meets all of the following criteria:

  • In-range INR (i.e., between 2 and 3) on a stable dose of warfarin or low molecular weight heparin
  • No active bleeding or pathological condition that is associated with a high risk of bleeding
• No concurrent major surgery