Patients will be enrolled to each dose level in cohorts of 3. Dose level escalation/de-escalation will follow BOIN (Bayesian Optimal Interval) design rules based on analysis of dose-limiting toxicities (DLTs) that occur within the first two cycles of protocol treatment. Protocol treatment will continue until disease progression or intolerable toxicity.~Dose Levels:~Dose Level 1: 60 mg PCI-24781 BID (two times daily)~Dose Level 2: 100 mg PCI-24781 BID~Dose Level 3: 140 mg PCI-24781 BID~Primary Objectives~I. To evaluate the toxicities and determine the recommended dose of PCI-24781 with metronomic temozolomide in subjects with recurrent high grade glioma, [grade III or IV glioma (glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma)].~Secondary Objectives~I. To evaluate changes in the acetylation of peripheral blood mononuclear cell (PBMC) histones H3 and H4 during treatment II. To evaluate for acetylation of histones H3 and H4 using peripheral blood exosomes III. To evaluate progression-free and overall survival of subjects with recurrent high grade glioma treated with therapy with PCI-24781 with metronomic temozolomide. Subjects with stable or responsive disease after every 2 cycles will continue on therapy until intolerance or progressive disease.~IV. To descriptively examine quality of life (QOL) using EORTC QLQ-C30, QLQ-BN20 during treatment.~V. To characterize the pharmacokinetics (PK) of PCI-24781, temozolomide, and the combination of the 2 drugs.~VI. To measure tumor response. VII. To correlate molecular profiles with tumor response.
The goal of this clinical trial is to learn about treatment for a type of brain cancer called glioma. This clinical trial is for people with glioma who have been cancer-free for a period of time but their cancer has come back. The primary goals of this clinical trial are the following:~To determine the recommended dose of PCI-24781 with metronomic temozolomide~To evaluate side effects associated with using PCI-24781 with metronomic temozolomide