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来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 具体目标 第一阶段： 1. 确定OSI-774（厄洛替尼; TarcevaTM）联合CCI-779（替西罗莫司）治疗未服用酶诱导抗癫痫药物（EIAED）的复发性恶性胶质瘤患者的最大耐受剂量（MTD）。 2. 描述OSI-774（厄洛替尼）和CCI-779（替西罗莫司）的安全性特征。 3. 描述OSI-774（厄洛替尼）和CCI-779（替西罗莫司）的药代动力学特征。 第二阶段： 主要目的： 1. 通过6个月无进展生存期测定OSI-774（厄洛替尼）和CCI-779（替西罗莫司）在复发性恶性胶质瘤患者中的疗效。 次要目标： 1. 总无进展生存期 2. 响应 探索性目标： 1. 探索治疗反应与肿瘤分子表型的相关性。 2. 确定OSI-774（厄洛替尼）和CCI-779（替西罗莫司）是否抑制接受手术的恶性胶质瘤患者的肿瘤标本中的EGFR和mTOR以及PI 3 K-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).