PS-341 IN PATIENTS WITH ADVANCED MALIGNANCIES AND RENAL DYSFUNCTION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项由ctep发起的器官功能障碍工作组开展的多中心一期研究。本研究的目的是：1)确定PS-341在晚期恶性肿瘤和轻度、中度或重度肾功能不全患者中的药代动力学和药效学特征；2)评价PS-341在不同程度肾功能不全患者中的安全性、耐受性和最大耐受剂量。受试者将根据肌酐清除率的测量分为5个治疗组。每个组的起始剂量不同。受试者将在第1、4、8和11天静脉滴注生理盐水30分钟，随后一周不进行治疗。一个周期为21天，周期可重复，直至疾病进展。仅在第1周期，受试者将在GCRC接受治疗，并提取药代动力学样本。剂量将根据方案中详述的剂量递增计划增加。剂量不会在任何个体患者中增加。本研究将在美国11个医疗中心共招募约69名受试者（本站点预计有10名受试者）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a multi-center, Phase I study of the CTEP-sponsored Organ Dysfunction Working Group. The objectives of this study are to: 1) identify the pharmacokinetic and pharmacodynamic profile of PS-341 in patients with advanced malignancy and mild, moderate or severe renal insufficiency, and 2) evaluate the safety, tolerability, and the maximum tolerated dose of PS-341 for patients with varying degrees of renal insufficiency. Subjects will be divided into 5 treatment groups based on creatinine clearance measurements. Each group will have a different starting dose of PS-341. Subjects will receive PS-341 through an IV infusion of normal saline over 30 minutes on Days 1, 4, 8 and 11, followed by a week without treatment. One cycle is 21 days and cycles may be repeated until disease progression. During Cycle 1 only, subjects will receive treatment at the GCRC and pharmacokinetic samples will be drawn. Doses will be increased according to the dose escalation plan detailed in the protocol. Doses will not be escalated in any individual patient. This study will enroll a total of approximately 69 subjects at 11 U.S. medical centers (10 subjects are expected at this site).