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

加州大学洛杉矶分校 IRB（待定）“Bay 43-9006（索拉非尼）组合的 I/II 期研究

• 批准号: 7606839
• 负责人: TIMOTHY CLOUGHESY
• 金额: $ 0.55万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-21 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606839
• 关键词: Antiepileptic Agents; BAY 43-9006; BAY 54-9085; Biological Markers; Blood; CCI-779; Clinical; Computer Retrieval of Information on Scientific Projects Database; Diagnosis; Dose; Drug Interactions; Drug Kinetics; Enzymes; Excision; Funding; Glioblastoma; Grant; Institution; Laboratory Study; Maximum Tolerated Dose; Measures; Molecular Target; Outcome; Patients; Pharmaceutical Preparations; Phase; Progression-Free Survivals; Protocols documentation; R115777 (Zarnestra); Recurrence; Research; Research Ethics Committees; Research Personnel; Resources; Safety; Signal Transduction Pathway; Source; Time; Tissues; United States National Institutes of Health; gliosarcoma; response; tumor

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.

这个子项目是许多研究子项目中的一个 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。 具体目标： 第一阶段： 1. 确定R115777、OSI-774或CCI-779联合固定剂量BAY 43-9006治疗未服用酶诱导抗癫痫药物（EIAED）的复发性胶质母细胞瘤或胶质肉瘤患者的最大耐受剂量。 2. 表征R115777-BAY 43-9006、OSI-774-BAY 43-9006和CCI-779-BAY 43-9006双联复方制剂在复发性胶质母细胞瘤或胶质肉瘤患者中的安全性特征。 3. 为了表征这些双联组合的药代动力学，评价每种药物的单药药代动力学，然后评价组合药代动力学，以确定药物-药物相互作用。 第2阶段： 1. 通过6个月无进展生存期测定每种双联治疗在复发性胶质母细胞瘤或胶质肉瘤患者中的疗效。 2. 通过12个月生存期和客观肿瘤缓解来确定每种双药组合在复发性胶质母细胞瘤或胶质肉瘤患者中的疗效。 3. 进一步表征每种双联体组合的安全性特征。 4. 在II期患者亚组中表征每种双联复方制剂的药代动力学，以进一步确定可能的药物相互作用。 5. 通过使用方案治疗开始前（从诊断或后续肿瘤切除时）获得的组织块进行免疫组织化学分析，检查信号转导通路的组织标志物，进行探索性相关实验室研究。 6. 对于分子靶向组合相关（MTC 2）研究计划：确定肿瘤和血液生物标志物与靶向药物联合治疗患者的临床结局之间的关系。