PS 341 IN THE TREATMENT OF RECURRENT GLIOMAS

PS 341 治疗复发性神经胶质瘤

• 批准号: 7603179
• 负责人: BURTON L NABORS
• 金额: $ 0.11万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603179
• 关键词: Adult; Aftercare; Anticonvulsants; Blood specimen; Computer Retrieval of Information on Scientific Projects Database; Cytochrome P450; Dose; Enzymes; Funding; Glioma; Grant; Hepatic; Hour; Infusion procedures; Institution; Maximum Tolerated Dose; Measurement; Multienzyme Complexes; Operative Surgical Procedures; PS341 cpd; Pharmaceutical Preparations; Phase; Recurrence; Research; Research Personnel; Resources; Route; Sampling; Screening procedure; Source; Surgical Decompression; Treatment Protocols; United States National Institutes of Health; Week; angiogenesis; inhibitor/antagonist; multicatalytic endopeptidase complex; tumor; tumor growth

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. Long-term objectives are 1) To determine the maximum tolerated dose of PS-341 when administered in a twice weekly regimen to adults with recurrent glioma, receiving (Group A) or not receiving (Group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex. 2) To describe the biologic activity of PS-341 by this route of administration, by measurement of proteasome 20S activity, and to determine the effects of hepatic enzyme inducing drugs, such as the anticonvulsants on the biologic activity. 3) To determine proteasome 20S activity in tumor samples after treatment with PS-341 at the MTD in 15 subjects (Phase B). Proteosome inhibitors can act through multiple mechanisms to arrest tumor growth, tumor spread and angiogenesis. In Phase A subjects will be dosed twice weekly x 4 weeks, then off 2 weeks. Study drug will be escalated in a stepwise fashion in groups of 3 subjects. Dose escalations will proceed independently in subjects receiving anticonvulsant medication (Group A) and those not receiving anticonvulsant medications (Group B). Study drug will be escalated for subjects in Group A and B until a DLT occurs. Blood samples will be drawn at screening, baseline and x 4 during 1st 24 hours after infusion for cycle 1 only. Phase B subjects must need surgical decompression of their recurrent glioma and receive 1 IV dose of study drug immediately prior to surgery. Tumor will be analyzed for 20S proteasome analysis.

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 长期目的是：1）确定复发性胶质瘤成人患者接受（A组）或未接受（B组）已知由P450肝酶复合物代谢的抗惊厥药每周两次给药方案时PS-341的最大耐受剂量。2)通过测定蛋白酶体20 S活性，描述PS-341通过该给药途径的生物活性，并确定肝酶诱导药物（如抗惊厥药）对生物活性的影响。3)确定15例受试者接受MTD PS-341治疗后肿瘤样本中的蛋白酶体20 S活性（B期）。蛋白酶体抑制剂可以通过多种机制来阻止肿瘤生长、肿瘤扩散和血管生成。在A阶段，受试者将每周给药两次x4周，然后停药2周。研究药物将以3例受试者为一组逐步递增。在接受抗惊厥药物治疗的受试者（A组）和未接受抗惊厥药物治疗的受试者（B组）中，剂量递增将独立进行。A组和B组受试者的研究药物剂量将递增，直至发生DLT。仅在第1周期，将在筛选、基线和输注后第1个24小时内第4次采集血样。B期受试者必须对其复发性胶质瘤进行手术减压，并在手术前立即接受1剂研究药物IV给药。将对肿瘤进行20 S蛋白酶体分析。