. Author manuscript; available in PMC: 2020 Apr 1.

Published in final edited form as: Clin Trials. 2019 Jan 28;16(2):165–175. doi: 10.1177/1740774518824539

Table 1.

Eligibility criteria

Inclusion Criteria	Exclusion Criteria
• Age ≥ 18 years at diagnosis. • Diagnosis of rectal adenocarcinoma. • Radiologically measurable or clinically evaluable disease as defined by protocol. • ECOG Performance Status (PS): 0, 1 or 2. • For this patient, the standard treatment recommendation in the absence of a clinical trial would be combined modality neoadjuvant chemoradiation followed by curative intent surgical resection. • Candidate for sphincter-sparing surgical resection prior to initiation of neoadjuvant therapy according to the primary surgeon. • Clinical Stage: T2N1, T3N0, T3N1. • N2 disease is to be estimated as four or more lymph nodes that are ≥10 mm. • Clinical staging should be estimated based on the combination of the following assessments: physical exam by the primary surgeon, CT or PET/CT scan of the chest/abdomen/pelvis and either a pelvic MRI or an ultrasound (ERUS). If a pelvic MRI is performed, it is acceptable to perform CT of the chest/abdomen, omitting CT imaging of the pelvis. • The following laboratory values obtained ≤ 28 days prior to registration. • Absolute neutrophil count (ANC) ≥ 1500/mm3 • Platelet count ≥ 100,000/mm3 • Hemoglobin > 8.0 g/dL • Total bilirubin ≤ 1.5 × upper limit of normal (ULN) • SGOT (AST) ≤ 3 × ULN • SGPT (ALT) ≤ 3 × ULN • Creatinine ≤1.5 × ULN • Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only. • Patient of child-bearing potential is willing to employ adequate contraception. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom). • Provide informed written consent. • Willing to return to enrolling medical site for all study assessments. • Primary rectal tumors that are within 5–12 cm of the anal verge (Dropped in a protocol amendment)	• Clinical T4 tumors. • Primary surgeon indicates need for abdominoperineal resection (APR) at baseline. • Evidence that the tumor is adherent to or invading the mesorectal fascia on imaging studies such that the surgeon would not be able to perform an R0 resection (one with negative margins). • Tumor is causing symptomatic bowel obstruction (patients who have had a temporary diverting ostomy are eligible). • Chemotherapy within 5 years prior to registration. (Hormonal therapy is allowable if the disease-free interval is ≥ 5 years.) • Any prior pelvic radiation. • Other invasive malignancy ≤ 5 years prior to registration. Exceptions are colonic polyps, nonmelanoma skin cancer, ductal carcinoma in situ, bladder carcinoma in situ, or carcinoma-in-situ of the cervix. • Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. • Pregnant women • Nursing women • Men or women of childbearing potential who are unwilling to employ adequate contraception • Co-morbid illnesses or other concurrent disease which, in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

Inclusion Criteria

Exclusion Criteria

• Age ≥ 18 years at diagnosis.
• Diagnosis of rectal adenocarcinoma.
• Radiologically measurable or clinically evaluable disease as defined by protocol.
• ECOG Performance Status (PS): 0, 1 or 2.
• For this patient, the standard treatment recommendation in the absence of a clinical trial would be combined modality neoadjuvant chemoradiation followed by curative intent surgical resection.
• Candidate for sphincter-sparing surgical resection prior to initiation of neoadjuvant therapy according to the primary surgeon.
• Clinical Stage: T2N1, T3N0, T3N1.
    • N2 disease is to be estimated as four or more lymph nodes that are ≥10 mm.
    • Clinical staging should be estimated based on the combination of the following assessments: physical exam by the primary surgeon, CT or PET/CT scan of the chest/abdomen/pelvis and either a pelvic MRI or an ultrasound (ERUS). If a pelvic MRI is performed, it is acceptable to perform CT of the chest/abdomen, omitting CT imaging of the pelvis.
• The following laboratory values obtained ≤ 28 days prior to registration.
    • Absolute neutrophil count (ANC) ≥ 1500/mm3
    • Platelet count ≥ 100,000/mm3
    • Hemoglobin > 8.0 g/dL
    • Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
    • SGOT (AST) ≤ 3 × ULN
    • SGPT (ALT) ≤ 3 × ULN
    • Creatinine ≤1.5 × ULN
• Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
• Patient of child-bearing potential is willing to employ adequate contraception. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom).
• Provide informed written consent.
• Willing to return to enrolling medical site for all study assessments.
• Primary rectal tumors that are within 5–12 cm of the anal verge (Dropped in a protocol amendment)

• Clinical T4 tumors.
• Primary surgeon indicates need for abdominoperineal resection (APR) at baseline.
• Evidence that the tumor is adherent to or invading the mesorectal fascia on imaging studies such that the surgeon would not be able to perform an R0 resection (one with negative margins).
• Tumor is causing symptomatic bowel obstruction (patients who have had a temporary diverting ostomy are eligible).
• Chemotherapy within 5 years prior to registration. (Hormonal therapy is allowable if the disease-free interval is ≥ 5 years.)
• Any prior pelvic radiation.
• Other invasive malignancy ≤ 5 years prior to registration. Exceptions are colonic polyps, nonmelanoma skin cancer, ductal carcinoma in situ, bladder carcinoma in situ, or carcinoma-in-situ of the cervix.
• Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects.
    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid illnesses or other concurrent disease which, in the judgment of the clinician obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.