? The competing renewal of the Orphan Products Development grant FD-R-002150-03 is submitted jointly by New York University School of Medicine (NYUSM) and the University of Southern California (USC) in Los Angeles. The proposal includes the ongoing, investigator-initiated study of a fluoropyrimidine agent FUDR. In the non-label new orphan indication, FUDR is delivered IP and studied in adjuvant settings in patients with resected locally advanced gastric/GEJ adenocarcinoma: (a) the safety and efficacy of IP FUDR is studied as one therapy and one non-label indication in the currently conducted Phase 2 trial, combining surgery, IP FUDR, and chemoradiation; (b) the investigators plan to continue the studies, establish clinical integration of the IP FUDR modality, and evaluate IP treatment efficacy in a randomized Phase 2 trial. Planned study will combine chemotherapy in the induction with surgery and adjuvant IP FUDR plus systemic chemotherapy. Both clinical trials should provide data essential for the Food and Drug Administration (FDA) to approve FUDR for lP adjuvant chemotherapy in patients with locally advanced gastric/GEJ adenocarcinoma, who receive potentially curative gastric resection and are eligible for combined-modality treatment. The primary aim of the proposed Phase 2 randomized study is to estimate the time of recurrence-free survival (RFS) in each of the two groups of patients either treated with lP FUDR or without FUDR treatment. The secondary aim of the trial is to apply Simon 2-stage design to monitor the rate of Grade 3-4 unresolved toxicities that result in cancellation of further protocol treatments, to describe the overall survival (OS) rate by Kaplan-Meier curve, and to evaluate treatment-failing patients in terms of sites of remission. All adverse events will be summarized regardless to causal relationship and by causal relationship to the study drug. After completion of Phase 2 randomized study, with estimates available for advanced statistical design, a follow-up Phase 3 trial will be designed and initiated. As an integral component, the proposal is addressing human subject protection, informed consent of trial patients, evaluation of potential risks and benefits of the trial, and gender, ethnical and racial representation. ? ?
