The Radiation Oncology-Biology Integration Network (ROBIN) Molecular Characterization Trial (MCT) of Standard Short Course Radiotherapy for Rectal Cancer

Inclusion Criteria:

• Histologically confirmed diagnosis of adenocarcinoma of the rectum

• Age ≥ 18 years

• ECOG performance status 0-1

• cT2-T3N0 or cT1-3N1

• Rectal cancer amenable to total mesorectal excision

• No evidence of distant metastases

• No prior pelvic radiation therapy

• No prior chemotherapy or surgery for rectal cancer

• No infections requiring systemic antibiotic treatment

• Hgb >8.0 gm/dL, PLT > 150,000/mm3, total bilirubin ≤ 1.5x upper limit of normal, AST ≤ upper limit of normal, ALT ≤ 3x upper limit of normal

• Patients must read, agree to, and sign a statement of informed consent prior toparticipation in this study. Patients who do not read or understand English oreligible but must have the consent form read to them in its entirety by an officialtranslator. Informed consent for non-literate or non-English speaking patients maynot be obtained by using a relative or a member of the patient's clinical team as atranslator.

• Female participants or reproductive potential, defined as not surgically sterilizedand between menarche and 1 year post menopause, must have a negative serum pregnancytest within 4 weeks prior to initiation of study treatment.

• Women with childbearing potential who are negative for pregnancy (urine or blood)and who agree to use effective contraceptive methods. A woman of childbearingpotential is defined by one who is biologically capable of becoming pregnant.Reliable contraception should be used from trial screening and must be continuedthroughout the study.

Exclusion Criteria:

• Recurrent rectal cancer

• Primary unresectable rectal cancer is defined as a primary rectal tumor which, onthe basis of either physical exam or pelvic MRI, is deemed to be adherent or fixedto adjacent pelvic structures (en bloc resection will not be achieved with negativemargins).

• cT4 will be excluded.

• ≥4 regional lymph nodes each ≥10 mm on pelvic MRI

• Patients who have received prior pelvic radiotherapy

• Patients with prior allogenic stem cell or solid organ transplantation.

• Patients receiving treatment with systemic immunosuppressive medication (including,but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate,thalidomide, and antitumor necrosis factor-α agents) administered at >10 mg/dayprednisone or equivalent within 2 weeks prior to initiation of study treatment.

• Patients with any other concurrent medical or psychiatric condition or diseasewhich, in the investigator's judgment would make them inappropriate candidates forentry into this study

• Patients receiving other anticancer or experimental therapy. No other experimentaltherapies (including chemotherapy, radiation, hormonal treatment, antibody therapy,immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrixmetalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody, orother experimental drugs) of any kind are permitted while the patient is receivingstudy treatment.

• Women who are pregnant or breastfeeding. Women of childbearing potential who areunwilling or unable to use an acceptable method of birth control to avoid pregnancyfor the entire study period and for up to four weeks after the study.