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).