PS-341 IN PATIENTS WITH ADVANCED MALIGNANCIES AND RENAL DYSFUNCTION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这是一项由CTEP赞助的器官功能障碍工作组的多中心第一阶段研究。这项研究的目的是：1)确定PS-341在晚期恶性肿瘤和轻、中、重度肾功能不全患者中的药代动力学和药效学特征；2)评估PS-341对不同程度肾功能不全患者的安全性、耐受性和最大耐受量。受试者将根据内生肌酐清除量被分成5个治疗组。每组的PS-341起始量都不同。受试者将在第1、4、8和11天通过静脉滴注生理盐水30分钟接受PS-341，随后一周不治疗。一个周期是21天，可以重复周期，直到疾病进展。仅在周期1期间，受试者将在GCRC接受治疗，并将抽取药代动力学样本。将根据议定书中详细的剂量升级计划增加剂量。任何个别患者的剂量都不会增加。这项研究将在11个美国医疗中心招募大约69名受试者(本网站预计有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).