UCLA IRB (PENDING) "A PHASE I/II STUDIES OF BAY 43-9006 (SORAFENIB) IN COMBIN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 具体目标： 第一阶段： 1.确定R115777、OSI-774或CCI-779与固定剂量的BAY 43-9006联合应用于未服用酶诱导抗癫痫药物(EIAEDs)的复发性胶质母细胞瘤或胶质肉瘤患者的最大耐受量。 2.研究R115777-BAY 43-9006、OSI-774-BAY 43-9006和CCI-779-BAY 43-9006联合化疗治疗复发性胶质母细胞瘤或胶质肉瘤的安全性。 3.通过评价各药物的单药药代动力学，再结合药代动力学来确定药物与药物的相互作用，以确定这些双联药物的药代动力学。 第二阶段： 1.以复发性胶质母细胞瘤或胶质肉瘤患者的6个月无进展生存期为指标，确定每种方案的疗效。 2.以复发性胶质母细胞瘤或胶质肉瘤患者的12个月生存期和客观肿瘤反应为指标，确定每种化疗方案的疗效。 3.进一步表征每种双联组合的安全性。 4.在II期患者的子集中表征每种二联体组合的药代动力学，以进一步确定可能的药物-药物相互作用。 5.从诊断时或随后的肿瘤切除开始，通过免疫组织化学分析检测信号转导通路的组织标志物，进行探索性的相关实验室研究。 6.分子靶向联合相关(MTC2)研究计划：确定联合靶向治疗的患者肿瘤与血液生物标志物和临床结果之间的关系。

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. SPECIFIC AIMS: Phase I: 1. To define the maximum tolerated dose of R115777, OSI-774, or CCI-779 in combination with a fixed dose of BAY 43-9006, in patients with recurrent glioblastoma or gliosarcoma who are not taking enzyme-inducing antiepileptic drugs (EIAEDs). 2. To characterize the safety profile of the doublet combinations of R115777-BAY 43-9006, OSI-774-BAY 43-9006 and CCI-779-BAY 43-9006 in patients with recurrent glioblastoma or gliosarcoma. 3. To characterize the pharmacokinetics of these doublet combinations, evaluating single agent pharmacokinetics of each agent then the combination pharmacokinetics to determine drug-drug interactions. Phase II: 1. To determine the efficacy of each of the doublet combinations in patients with recurrent glioblastoma or gliosarcoma as measured by 6-month progression-free survival. 2. To determine the efficacy of each of the doublet combinations in patients with recurrent glioblastoma or gliosarcoma as measured by 12-month survival and objective tumor response. 3. To further characterize the safety profile of each of the doublet combinations. 4. To characterize the pharmacokinetics of each of the doublet combinations in a subset of the phase II patients to further define possible drug-drug interactions. 5. To perform exploratory correlative laboratory studies by examining tissue markers of signal transduction pathways by immunohistochemical analysis using tissue blocks obtained prior to initiation of protocol therapy, either from the time of diagnosis or subsequent tumor resection. 6. For the Molecular Targeted Combinations Correlative (MTC2) Study Initiative: To determine the relationship between tumor and blood biomarkers and clinical outcome of patients treated with the combination of targeted agents.