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 ULN, then creatinine clearance must be >= 50 mL/mm
• Within 4 weeks prior to registration, serum bilirubin must be = = 1 must undergo a 24-hour urine collection which must be an adequate collection and must demonstrate = 2 gm/dl
• Absence of clinical evidence of high-grade (lumen diameter 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 must undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate 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