NABTT 0401 - BAY 43-9006 FOR PATIENTS WITH GLIOMA

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。第一个目标是确定BAY 43-9006在接受或不接受已知由P450肝酶复合物代谢的抗惊痫药物的成人复发性恶性胶质瘤患者中的最大耐受剂量（MTD）。第二个目标是评估和估计剂量相关的毒性。第三，描述该给药途径的药代动力学，测量BAY 43-9906，评估服用酶诱导药物与未服用酶诱导药物患者的药代动力学差异。最后，估计总体存活率。RAS/raf信号通路是对生长信号和血管生成因子反应的重要中介。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已经在多种肿瘤类型的多个I期和II期研究中进行了评估。BAY 43-9006将连续4周口服BID。起始剂量为200mg BID。本研究将根据细胞色素p450诱导抗惊厥药物的使用情况对患者进行分层。研究的每组每组3例患者（A组3例，B组3例）将以200 mg BID的起始剂量治疗，x 4周，直到肿瘤进展。剂量将逐步增加，在假定的最长治疗时间扩大到总共6名患者。

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. 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.