Preservation of Organs in Participants with Early Rectal Cancer

Inclusion Criteria

• Histologically proven adenocarcinoma of the lower rectum (lower border =< 6 cm from anal verge as assessed by pelvic magnetic resonance imaging [MRI]).
• Clinical stage T1N0, T2N0, T3N0; high risk T1 and low risk T3 stage patients are also allowed. Clinical staging should be estimated based on the combination of the following assessments: physical exam by the primary surgeon, computed tomography (CT) chest/abdomen/pelvis or positron-emission tomography (PET)/CT along with pelvic MRI. Endoscopic rectal ultrasound (ERUS) can be added for staging assessment if MRI is inconclusive. Since MRI is performed, it is acceptable to perform CT of the chest/abdomen, omitting CT imaging of the pelvis.
• No prior therapy for rectal cancer.
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Leukocytes >= 3,000/mcL.
• Absolute neutrophil count >= 1,500/mcL.
• Platelets >= 100,000/mcL.
• Total bilirubin =< 1.5 times upper limit of normal (ULN).
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) (serum glutamic oxaloacetic transaminase [SGOT]/serum glutamic pyruvic transaminase [SGPT]) =< 3 times institutional normal limits.
• Creatinine < 1.5 times ULN.
• Creatinine clearance >= 60 Ml/min/1.73 m^2 for patients with creatinine levels above institutional normal.
• Ability to understand and willingness to sign a written informed consent and HIPAA consent document.

Exclusion Criteria

• Patients with contraindication to use leucovorin calcium (calcium folinate), 5-fluorouracil, and oxaliplatin (FOLFOX) chemotherapy and pelvic radiation.
• Low risk T1 tumors that fulfill all of the following - size < 4 cm, lack of lymphovascular invasion and well differentiated histology, are excluded.
• High risk T3 tumors that fulfill any of the following – circumferential tumor, extension into mesorectal fascia > 5 mm, prediction of positive circumferential resection margin, are also excluded.
• T4, node positive or advanced rectal adenocarcinoma. Node positivity defined as nodes greater than 1 cm in short axis with loss of uniform cortex/fatty hilum.
• Patients receiving other investigational agents.
• Patients who have had chemotherapy (for other malignancies) within 3 years prior to registration.
• Patients with any prior pelvic radiation therapy.
• Prior malignancies requiring systemic therapy within the last 3 years (as prior therapy can increase toxicity of current chemo regimen, those patients should be excluded).
• History of allergic reactions attributed to compound of similar chemical or biologic composition to the agents used in this study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with chemotherapeutic drugs. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Pregnant or breast feeding.