GW572016 to Treat Recurrent Malignant Brain Tumors

Background: \- One of the most critical challenges facing glioblastoma translational research is developing ways to predict, based on a patient's biopsy, which targeted inhibitor is most likely to provide benefit. The studies outlined in this proposal are designed to determine which glioblastoma patients are most likely to benefit from GW572106, and may provide a blueprint for analyzing promising new pathway inhibitors in the future. We anticipate that these studies will serve as the basis for biological endpoint based trials in the future. Thus, the overall goal is to evaluate the efficacy of GW572016 in the treatment of recurrent malignant gliomas in patients who are candidates for re-resection. Objective: * Determine the 6-month progression-free survival rate for patients with recurrent or progressive glioblastoma treated with GW572016. * Determine whether GW572016 inhibits the phosphorylation of its cellular targets EGFR and HER2, and the downstream PI3K-AKT and RAS-ERK signaling pathways in glioblastoma patients in vivo. * Determine tumor concentrations of GW572016. * Assess overall progression free survival and safety. Eligibility: * Patients with histologically proven intracranial tumors to include only glioblastoma multiforme (GBM) and Gliosarcoma (GS). Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a GBM is made. * Patients must be candidates for surgical re-resection (total, or sub-total) in order to be eligible for this study. Following surgery, a scan should be done no later than 96 hours * Patients may be on a non-enzyme-inducing anti-epileptic drugs (Non-EIAED's). They may not be on EIAED's. If previously on an EIAED, patient must be off of it for two weeks prior to initiation of pre-operative drug. Design: * A Pre-Treatment blood sample (10ml) will be obtained in all patients for genotyping * Pre- Operative: GW572016 will be administered at a starting dose of 750 mg orally BID daily on an outpatient basis for 7-10 days. (This range is to allow flexibility for planning surgery). GW572016 will be continued up to and including the evening before surgery. * At the time of surgery 10ml of blood will be collected in EDTA containing tubes for pharmacodynamic analysis * Treatment may be instituted postoperatively as soon as patients have recovered from effects of surgery and demonstrated wound healing. Treatment with GW572016 post-operatively should start no later than 28 days after surgery. GW572016 will be administered at a starting dose of 750 mg orally BID daily on an outpatient basis. GW572016 will be administered continuously; however, for the purposes of protocol evaluations, a cycle will be defined as 28 days.