PHASE II STUDY OF INTRAPERITONEAL FLOXURIDINE IN GASTRI*

描述(由申请人提供)： 孤儿产品开发补助金FD-R-002150-03的竞争性续签由纽约大学医学院(NYUSM)和位于洛杉矶的南加州大学(USC)联合提交。该提案包括正在进行的、由研究人员发起的对氟代嘧啶类药物FUDR的研究。在非标签新的孤儿适应症中，FUDR被给予IP，并在辅助环境下对局部切除的晚期胃/GEJ腺癌患者进行研究：(A)在目前进行的第二阶段试验中，IP FUDR作为一种疗法和一种非标签适应症进行了安全性和有效性研究，该试验结合了手术、IP FUDR和化疗；(B)研究人员计划继续进行研究，建立IP FUDR模式的临床整合，并在随机的第二阶段试验中评估IP治疗的疗效。计划中的研究将结合诱导和手术中的化疗以及辅助性IP FUDR和全身化疗。这两项临床试验都应该为食品和药物管理局(FDA)批准FUDR用于局部进展期胃/GEJ腺癌患者的LP辅助化疗提供必要的数据，这些患者接受了潜在的根治性胃切除，并有资格接受综合治疗。拟议的第2期随机研究的主要目的是估计接受LP FUDR治疗或未接受FUDR治疗的两组患者的无复发存活(RFS)时间。这项试验的次要目标是应用Simon 2阶段设计来监测导致取消进一步方案治疗的3-4级未解决毒性的比率，通过Kaplan-Meier曲线描述总体存活率(OS)，并根据缓解地点来评估治疗失败的患者。所有不良事件都将按因果关系和与研究药物的因果关系进行总结。在第二阶段随机研究完成后，将设计和启动后续第三阶段试验，估计数可用于高级统计设计。作为一个组成部分，该提案涉及人类受试者保护、试验患者的知情同意、对试验的潜在风险和好处的评估以及性别、族裔和种族代表性。

DESCRIPTION (provided by applicant): 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.