Testing the Addition of a Radiation Sensitizing Drug, IPdR, to the Usual Chemotherapy Treatment (Capecitabine) During Radiation Therapy for Rectal Cancer

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of oral (PO) ropidoxuridine (IPdR) when administered with capecitabine (825 mg/m\^2 twice daily \[BID\]) and radiation therapy (RT) (50.4 Gy in 28 fractions). II. To determine the toxicities Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 of the combined modality therapy, IPdR + capecitabine + RT. SECONDARY OBJECTIVES: I. To establish the pharmacokinetics (PK) of once daily (QD) IPdR when combined with capecitabine. II. To evaluate iododeoxyuridine (IUdR) incorporation in circulating granulocytes and correlate these levels with IPdR plasma PK and clinical/laboratory toxicities. III. To assess IUdR incorporation in tumor cells obtained from the surgical resection specimen and correlate IUdR incorporation in tumor cells with IPdR PK. IV. To assess IUdR incorporation in tumor cells obtained from the surgical resection specimen and correlate IUdR incorporation in tumor cells with tumor response as measured by pathological complete response (pCR) rate and neoadjuvant rectal (NAR) score. V. To determine the pCR rate of IPdR + capecitabine + RT at the IPdR MTD as a measure of anti-tumor activity. VI. To determine the NAR score of IPdR + capecitabine + RT at the IPdR MTD. EXPLORATORY OBJECTIVES: I. To explore the relationship between extent of exposure to RT and the development and severity of adverse events. II. To explore the drug/drug/metabolite interactions between capecitabine, IPdR, and their metabolites. OUTLINE: This is a phase IA, dose-escalation study of ropidoxuridine followed by a phase IB study. Patients receive ropidoxuridine PO QD over 7 days per week and capecitabine PO BID over 6 days per week for 6 weeks. Patients also undergo radiation therapy over 1 fraction per day for 5 days per week (Monday-Friday) during weeks 1-5 and for 3 days during week 6 in the absence of disease progression or unacceptable toxicity. Approximately 8-12 weeks after completion of treatment with ropidoxuridine, capecitabine, and radiation therapy, patients undergo standard of care surgery. After completion of study treatment, patients are followed up at 4 and 8-12 weeks following chemoradiation therapy.