Table 1.

Inclusion and exclusion criteria

Inclusion Criteria		Exclusion Criteria
General	Histologically confirmed diagnosis of adenocarcinoma of the rectum Patients must have clinical Stage II or III rectal adenocarcinoma defined as T4N0 or any T with node positive disease (any T, N +); also, T3N0 requiring APR or coloanal anastomosis Tumor site $\le 12\text{cm}$ from the anal verge Age $\ge$ 18 years No prior systemic chemotherapy, targeted therapy, or immunotherapy, or radiation therapy administered as treatment for colorectal cancer within the past 5 years Karnofksy $\ge$ 60%, ECOG $\le$ 2, ANC $\ge$ 1,500/mm3, Platelet $\ge$ 100,000/mm3, Creatinine $\le$ 1.5 × upper limit of normal OR Calc. Creatinine Clearance $\ge$ 50 mL/min, Total bilirubin $\le$ 1.5 × upper limit of normal, AST/ALT $\le$ 3 × upper limit of normal HIV infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment or cardiac function using the New York Heart Association Classification. Patients should be Class 2B or better	Recurrent rectal cancer Upper rectal cancers (distal margin of tumor $>$ 12 cm from the anal verge Prior distal sigmoid cancer with a low anastomosis Prior trans-anal excision Known mismatch repair deficient rectal adenocarcinoma Chronic concomitant treatment with strong inhibitors of CYP3A4 that can not be discontinued 14 days prior to study registration and for duration of the study Chronic concomitant treatment with strong inducers of CYP3A4 that can not be discontinued 14 days prior to study registration and for duration of the study
Consent	Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study. Patients who do not read or understand English are eligible but must have the consent form read to them in its entirety by an official translator, either from the study site or via phone interpreter. Informed consent for non-literate or non-English speaking patients may not be obtained by using a relative or a member of the patient’s clinical team as a translator. Consortium sites must follow federal, local, and institutional regulations to ensure that non-English speaking patients are consented appropriately	N/A
Women	Women of childbearing potential who are negative for pregnancy test (urine or blood), not nursing, and who agree to use effective contraceptive methods. A woman of childbearing potential is defined as a sexually mature female who has not undergone hysterectomy or bilateral oophorectomy and has not been postmenopausal for 12 consecutive months	Women are pregnant or breast-feeding. Women of childbearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for $\ge$ 9 months after the last dose of study drug
Men	Male subjects must also agree to effective contraception	Men who are unwilling or unable to use an acceptable method of birth control while in this study and for $\ge$ 6 months after the last treatment