NABTT 0401 - BAY 43-9006 FOR PATIENTS WITH GLIOMA

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。第一个目标是确定在接受或不接受已知由P450肝酶复合体代谢的抗惊厥药物的情况下，Bay 43-9006在接受或不接受抗惊厥治疗时的最大耐受量(MTD)。第二个目标是评估和估计与剂量相关的毒性。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和不服用酶诱导剂的患者之间的药代动力学差异。最后，估计总体存活率。RAS/RAF信号通路是细胞对生长信号和血管生成因子反应的重要中介。BAY 43-9006在体外对c-raf、野生型和突变型b-raf均有很强的抑制作用。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周口服申办。起始剂量为200毫克，每日2次。在这项研究中，患者将根据细胞色素P450诱导的抗惊厥药物的使用情况进行分层。在这项研究的每个队列中，每组3名患者(A组3名，B组3名)将接受200 mg的起始剂量，2次/d×4周，直到肿瘤进展。剂量将以循序渐进的方式逐步扩大到推定MTD的总共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.