Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma

Background: * Primary gliomas are an incurable disease in spite of aggressive multimodality therapy consisting of craniotomy, irradiation, and chemotherapy. Therapeutic options for patients with recurrent glioma are limited, and there is an unmet need to identify more effective agents. * LB100, a water-soluble small molecule novel protein phosphatase 2A (PP2A) inhibitor, was commercially developed through a Cooperative Research and Development Agreement (CRADA) based on our previous intramural research. This compound has shown to be effective in a variety of cancer types in both in vitro and in vivo models. Preclinical studies indicate LB100 has in vitro and in vivo activity as a single agent as well as potentiating the effect of cytotoxic agents including temozolomide, docetaxel, doxorubicin, and ionizing radiation. LB100 is active in combination with temozolomide or doxorubicin against xenografts of glioblastoma, neuroblastoma, pheochromocytoma, breast cancer, fibrosarcoma, and melanoma. * A complete phase I study of LB100 has established its safety and the recommended phase II dose (2.33 mg/m\^2, daily for three days every 3 weeks). * Although it is a polar compound, rodent studies suggest LB100 has activity in the brain. * Whether LB100 can across the human blood brain barrier (BBB), and at what concentration relative to the plasma level is not known. Characterizing these parameters is important because: * 1\) Our ongoing in vitro studies indicate that LB100 has distinct mechanisms of action at different drug concentrations (e.g., nM versus uM); * 2\) There are other brain tumors lacking effective medical therapies but without a BBB. Characterizing the LB100 BBB penetration profile will assist in defining its optimal clinical indication. Objective: -To determine the pharmacokinetic (PK) properties of LB100 in glioma tumor tissues. Eligibility: * Patients with histologically proven glioblastoma and grades II-III astrocytomas and oligodendrogliomas. * A clear clinical indication for another surgical resection must be present. * Subjects must be greater than or equal to 18 years old. * Karnofsky performance status of greater than or equal to 60%. * Patients must have adequate organ function. Design: * This is a two stage Phase II, open label, single institution study to determine the PK and pharmacodynamic (PD) profile of LB100. * The dose (established from a Phase I study) will be 2.33 mg/m\^2 delivered intravenously over 2 hours. * PK and PD effect of LB100 treated tissues will only be evaluated with pathologic confirmation of recurrent tumor. Resected material demonstrating chemoradiation treatment effect or inflammatory response will not be included in the analysis. * PK will be determined by quantitating LB100 in tumor tissues removed at various time points. * The primary endpoint is PK response, defined as a binary variable indicating the presence/absence of LB100 in tumor tissues. * PD effect is defined as statistically significant elevation of phospho-proteins in treated tumor tissues compared to untreated glioma specimens. Untreated inter-patient baseline variance and standard deviation (SD) will be calculated. Post-treatment PD effect difference greater than 2.5 times the baseline SD is statistically significant at the .05 significance level. Due to relatively small sample size, t-distribution is to be used to calculate the cutoff defining the PD response. * Up to 25 patients may be enrolled to obtain 8 evaluable subjects. A two-stage design will be used. Five patients will be initially treated. If at least one of five demonstrates PK activity, 3 additional subjects will be enrolled. PK effect will be declared to be significant if at least 2 of the 8 patients demonstrate a PK response (presence of LB100 in tumor tissue).