Bevacizumab, Radiation Therapy, and Combination Chemotherapy in Treating Patients Who Are Undergoing Surgery for Locally Advanced Nonmetastatic Rectal Cancer

Inclusion Criteria:

• Patients must have histologically confirmed, locally advanced, non-metastatic primary T3 or T4 adenocarcinoma of the rectum
• Patients must not have evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy
• Patients must not have intra-operative radiotherapy (IORT) or brachytherapy treatment to the pelvis
• The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 centimeters of the anal verge by proctoscopic examination
• Transmural penetration of tumor through the muscularis propria must be demonstrated by either of the following: computed tomography (CT) scan plus endorectal ultrasound, or a magnetic resonance imaging (MRI); an endorectal coil or pelvic MRI is allowed
• For the patient to be eligible, the surgeon must prospectively define the tumor as either initially resectable or potentially resectable after pre-operative chemoradiation; clinically resectable tumors are defined as completely resectable with negative margins based on routine examination of the non-anesthetized patient; patients whose tumors are not resectable are not eligible; before pre-operative (op) treatment, the surgeon should estimate and record the type of resection anticipated: pelvic exenteration, posterior pelvic exenteration, APR, LAR, or LAR/coloanal anastomosis

• Patients with tumors that are clinically fixed, clinical stage T4N0-2, M0 are eligible if it is believed that their tumors are potentially resectable after chemoradiation; based on the following:

  • Clinically fixed tumors on rectal examination with tumor adherent to the pelvic sidewall or sacrum
  • Sciatica attributed to sacral root invasion with CT scan/MRI evidence of the lack of clear tissue plane will be considered evidence of fixation
  • Hydronephrosis on CT scan or intravenous pyelogram (IVP) or ureteric or bladder invasion as documented by cystoscopy and cytology or biopsy, or invasion into prostate
  • Vaginal or uterine involvement
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• A surgical evaluation must confirm patient's ability to tolerate the proposed surgical procedure
• Patients must have a caloric intake > 1500 kilocalories/day (d)
• Within 4 weeks prior to registration, the patient's absolute neutrophil count (ANC) level must be >= 1,500/mm^3
• Within 4 weeks prior to registration, the patients platelet level must be >= 100,000/mm^3
• Within 4 weeks prior to registration, serum creatinine must be < 1.5 X upper limit of normal (ULN); if serum creatinine > 1.5 x ULN, then creatinine clearance must be >= 50 mL/mm
• Within 4 weeks prior to registration, serum bilirubin must be =< 1.5 X ULN
• Within 4 weeks prior to registration, alkaline phosphatase (alk phos) must be < 2 x ULN
• Within 4 weeks prior to registration, serum glutamic oxaloacetic transaminase (SGOT) must be < 2 x ULN
• Carcinoembryonic antigen (CEA) must be determined prior to initiation of therapy
• Within 4 weeks prior to registration, urine protein/creatinine (UPC) ratio must be < 1; patients with a ratio of >= 1 must undergo a 24-hour urine collection which must be an adequate collection and must demonstrate < 1 gram (gm) of protein in order to participate
• Within 4 weeks prior to registration, albumin must be >= 2 gm/dl
• Absence of clinical evidence of high-grade (lumen diameter < 1 cm) large bowel obstruction, unless diverting colostomy has been performed
• Eligible patients of reproductive potential (both sexes) must agree to use an accepted and effective method of contraceptive during study therapy and for at least 6 months after the completion of bevacizumab
• Women must not be pregnant or breast-feeding; all females of childbearing potential must have a serum pregnancy test to rule out pregnancy within 2 weeks of registration
• Patients must have had no prior chemotherapy for rectal cancer or pelvic irradiation therapy
• Patients with prior malignancies, including pelvic cancer, are eligible if they have been disease free for > 5 years; patients with prior in situ carcinomas are eligible provided there was complete removal
• Patients must have no active inflammatory bowel disease or other serious medical illness or disease that might limit the patient's ability to receive protocol therapy
• Patients with a history of cerebrovascular accident (CVA)/transient ischemic attack (TIA) at any time, or myocardial infarction/unstable angina within 12 months of study entry are not eligible
• Patients with > grade 1 peripheral neuropathy are not eligible
• Patients must have urine protein/creatinine (UPC) ratio of < 1.0; patients with a UPC ratio >= 1.0 must undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate < 1 gm of protein in order to participate
• Patients with a history of hypertension must measure < 150/90 mmHg and be on a stable regimen of anti-hypertensive therapy
• Patients with clinically significant peripheral vascular disease are not eligible

• Patients must not have any of the following:

  • Unstable angina (within 12 months of study entry)
  • New York Heart Association (NYHA) grade II or higher congestive heart failure
  • Evidence of bleeding diathesis/coagulopathy
  • Serious non-healing wound or bone fracture

• Patients with a history of the following within 28 days prior to registration are not eligible:

  • Abdominal fistula
  • Gastrointestinal perforation
  • Intrabdominal abscess

• Patients with a history of the following within 28 days prior to day 0 (first treatment day) are not eligible:

  • Major surgical procedure
  • Open biopsy
  • Significant traumatic injury
• Patients must not have core biopsy within 7 days prior to day 0 (first treatment day)

• Patients with prothrombin time (PT) (international normalized ratio [INR]) > 1.5 are not eligible, unless the patient is on full-dose anticoagulants; if so, the following criteria must be met for enrollment:

  • The subject must have an in-range INR (usually between 2 and 3), be on a stable dose of warfarin or on a stable dose of low molecular weight heparin
  • The subject must not have active bleeding or a pathological condition that is associated with a high risk of bleeding