NABTT 0401 - BAY 43-9006 FOR PATIENTS WITH GLIOMA

NABTT 0401 - BAY 43-9006 适用于神经胶质瘤患者

• 批准号: 7380475
• 负责人: BURTON L NABORS
• 金额: $ 0.78万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380475
• 关键词: NABTT; 0401; BAY; 43; 9006

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. The first objective is to determine the maximum tolerated dose (MTD) of BAY 43-9006 when administered to adults with recurrent malignant glioma, receiving or not receiving anti-convulsants known to be metabolized by the P450 hepatic enzyme complex. The second objective is to assess and estimate the dose-related toxicities. Thirdly, to describe the pharmacokinetics of this route of administration, measuring BAY 43-9906, and to assess the pharmacokinetic difference between patients taking enzyme-inducing agents and those who are not. And lastly, to estimate overall survival. The RAS/raf signaling pathway is an important mediator of responses to growth signals and angiogenic factors. BAY 43-9006 is a potent inhibitor of c-raf, and wild-type and mutant b-raf in vitro. Bay 43-9006 has been evaluated in multiple Phase I and Phase II studies in a variety of tumor types. BAY 43-9006 will be administered orally BID for 4 consecutive weeks. The starting dose will be 200 mg BID. Patients will be stratified according to the use of cytochrome P450-inducing anticonvulsants in this study. Three patients per cohort in each arm of the study (3 from Group A and 3 from Group B) will be treated at the starting dose of 200 mg BID x 4 weeks until tumor progression. The dose will be escalated in a stepwise fashion with an expansion to a total of 6 patients at the putative MTD.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。第一个目的是确定BAY 43-9006在复发性恶性胶质瘤成人患者中给药时的最大耐受剂量（MTD），接受或不接受已知由P450肝酶复合物代谢的抗惊厥药。第二个目的是评估和估计剂量相关毒性。第三，描述这种给药途径的药代动力学，测量BAY 43-9906，并评估服用酶诱导剂的患者与未服用酶诱导剂的患者之间的药代动力学差异。最后，评估总体生存率。RAS/raf信号通路是对生长信号和血管生成因子反应的重要介质。BAY 43-9006是体外c-raf、野生型和突变型b-raf的有效抑制剂。Bay 43-9006已在多种肿瘤类型的多项I期和II期研究中进行了评价。BAY 43-9006将口服给药，BID，连续4周。起始剂量为200 mg BID。将根据本研究中细胞色素P450诱导抗惊厥药的使用对患者进行分层。研究的每个组中每个队列的3名患者（来自A组的3名和来自B组的3名）将以200 mg BID x 4周的起始剂量治疗，直至肿瘤进展。剂量将以逐步方式递增，在假定的MTD下扩展至总共6例患者。