5-FU, Aflibercept, and Radiation (RT) for Preoperative and Postoperative Patients With Stage II/III Rectal Cancer

Inclusion criteria

• Patients with histologically confirmed stage II or III rectal cancer (adenocarcinoma)
• Patients must be candidates for preoperative chemoradiation
• Male or female patients ≥18 years-of-age
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1
• Adequate hematologic, liver and renal function
• Male patients willing to use adequate contraceptive measures
• Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test <7 days prior to start of treatment
• Life expectancy ≥12 weeks
• Willingness and ability to comply with the trial and follow-up procedures
• Ability to understand the nature of this trial and give written informed consent.

Exclusion criteria

• Treatment with prior chemotherapy or radiation for rectal cancer.
• Patients who have received any other investigational agents within the 28 days prior to Day 1 of the study.
• Known to be human immunodeficiency virus positive or hepatitis B or C positive
• Women who are pregnant or breastfeeding
• History of acute myocardial infarction within the previous 6 months, uncontrolled hypertension (blood pressure >150/100 mmHg and/or diastolic blood pressure >100 mmHg), unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication (excluding atrial fibrillation), or ≥ Grade 2 peripheral vascular disease.
• History of hypertensive crisis or hypertensive encephalopathy.
• History of stroke or transient ischemic attack within the past 6 months.
• Significant vascular disease (eg, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to initiation of therapy.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months.
• Patients with symptomatic sensory or peripheral neuropathy (Grade 2 or above).
• Patients may not have received other agents, either investigational or marketed, that act by primary anti-angiogenic mechanisms.
• Prior malignancy (except for adequately treated basal-cell or squamous-cell skin cancers, in situ carcinomas, or low grade [Gleason score of 3+3 or less] localized prostate cancer) in the past 5 years.
• Patients with active concurrent infections or patients with serious underlying medical conditions.
• Patients receiving full-dose oral or parenteral/SC anticoagulation must be on a stable dosing schedule prior to enrollment; a coumadin dose must be stable for 1 week. If this cannot be achieved, the patient will be ineligible for enrollment.
• Major surgical procedure or significant traumatic injury within 28 days prior to study initiation, or anticipation of need for major surgical procedure during the course of the study.
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to initiation of therapy.
• Patients with proteinuria, as demonstrated by a urine protein of 2+ or greater at screening. If 2+ or greater proteinuria, a 24-hour urine can be obtained, and if the result is <1 gm/24 hours, the patient is eligible.
• Any non-healing wound, ulcer, or bone fracture.
• Any clinical evidence or history of a bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
• History of hemoptysis (≥½ teaspoon of bright red blood per episode) within 1 month prior to initiation of therapy.
• History of any other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the