PHASE I/II STUDY OF OSI-774 (ERLOTINIB) AND CCI-779 (TEMSIROLIMUS) IN PATIENT

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OSI-774(erlotinib；TarcevaTM)联合CCI-779(替西罗莫司)治疗未服用酶诱导型抗癫痫药(EIAEDs)的复发恶性胶质瘤患者的最大耐受量(MTD)。 2.研究OSI-774(厄洛替尼)和CCI-779(替西罗莫司)的安全性。 3.研究厄洛替尼OSI-774和替西罗莫司CCI-779的药代动力学。 第二阶段： 主要目标： 1.以6个月无进展生存期为指标评价OSI-774(厄洛替尼)和CCI-779(替西罗莫司)治疗复发性恶性胶质瘤的疗效。 次要目标： 1.总体无进展生存 2.回应 探索性目标： 1.探讨治疗反应与肿瘤分子表型的关系。 2.确定OSI-774(厄洛替尼)和CCI-779(替西罗莫司)是否抑制恶性胶质瘤手术患者肿瘤标本中的EGFR和mTOR以及PI3K-AKT-mTOR和Ras-ERK信号通路。 3.OSI-774(厄洛替尼)和CCI-779(替西罗莫司)的肿瘤浓度。

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 (MTD) of OSI-774 (erlotinib; TarcevaTM) in combination with CCI-779 (temsirolimus) in patients with recurrent malignant glioma who are not taking enzyme-inducing anti-epileptic drugs (EIAEDs). 2. To characterize the safety profile of OSI-774 (erlotinib) and CCI-779 (temsirolimus). 3. To characterize the pharmacokinetics of OSI-774 (erlotinib) and CCI-779 (temsirolimus). Phase II: Primary Aim: 1. To determine the efficacy of OSI-774 (erlotinib) and CCI-779 (temsirolimus) in patients with recurrent malignant glioma as measured by 6-month progression-free survival. Secondary Aims: 1. Overall progression-free survival 2. Response Exploratory Aims: 1. To explore the association of response to treatment to the molecular phenotype of the tumor. 2. Determine whether OSI-774 (erlotinib) and CCI-779 (temsirolimus) inhibits EGFR and mTOR and the PI3K-AKT-mTOR and RAS-ERK signaling pathways in tumor specimens taken from malignant glioma patients undergoing surgery. 3. Tumor concentration of OSI-774 (erlotinib) and CCI-779 (temsirolimus).