A Phase I Study of Metronomic Temozolomide With Abexinostat (PCI-24781) for Patients With Recurrent High Grade Glioma

Inclusion Criteria: * Pathologically proven diagnosis of high grade (aka grade III or IV) glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma, gliosarcoma) * Prior radiation therapy and standard temozolomide; additional therapies for previous progressions are eligible (prior bevacizumab and Optune are allowed) * Three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression * 19 years of age or older (the age of consent in Nebraska) * Fully recovered from any toxicity of prior therapy that, in the opinion of the investigator, could impact tolerance to the study drug * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 * Adequate bone marrow reserve (ANC count ≥1,500/mm3, hemoglobin \> 8 g/dL, platelet count ≥100,000/mm3) * Adequate renal function (a serum creatinine that is at or below 2.0 mg/dL) * Adequate hepatic function (serum AST and ALT less than 1.5 times the upper limits of normal, serum alkaline phosphatase less than 2.5 times the upper limits of normal) * Able to provide written, informed consent * Females of child-bearing potential must have a negative pregnancy test within 7 days of initiating study (non-child bearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries) * Females of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and up to 6 months following treatment Exclusion Criteria: * Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of oral PCI-24781/Abexinostat, or put the study outcomes at undue risk * Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmia, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification * Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction * Immunotherapy, chemotherapy, radiotherapy, corticosteroids (at dosages equivalent to prednisone \> 20 mg/day) or experimental therapy (other than PCI-24781/Abexinostat PO) within 4 weeks before first dose of study drug * Concurrent use of enzyme-inducing antiepileptic drugs (phenytoin, phenobarbital, carbamazepine, felbamate, topiramate and oxcarbazepine) * Any other active malignancy other than nonmelanoma skin cancer or controlled prostate cancer * Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled active systemic infection (no testing is required for eligibility) * Creatinine \> 1.5 x institutional upper limit of normal (ULN); total bilirubin \> 1.5 x ULN (unless from Gilbert's disease), and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 x ULN * Pregnant or breast-feeding * Baseline ECG duration of the ventricular action potential corrected for heart rate (QTc interval) prolongation based on Fridericia's formula is \> 450 ms in males and \> 470 ms in females * Concomitant valproic acid use, or another histone deacetylases (HDAC) inhibitor * Receiving treatment with following medications and unable to discontinue treatment or switch medications prior to study enrollment: * Amiodarone (Cordarone, Pacerone) * Arsenic trioxide (Trisenox) * Chlorpromazine (Aralen) * Cisapride (Propulsid) * Clarithromycin (Biaxin) * Disopyramide (Norpace) * Dofetilide (Tikosyn) * Doperidol (Inapsine) * Erythromycin (EryTab, Erythrocin) * Flecanide (Tambocor) * Haloperidol (Haldol) * Ibutilide (Corvert) * Methadone (Methadose, Dolophine) * Moxifloxacin (Avelox) * Pentamidine (Pentam, Nebupent) * Pimozide (Orap) * Procainamide (Procan, Pronestyl) * Quinidine (Cardioquin, Quinaglute) * Sotalol (Betapace) * Thioridazine (Mellaril) * Vandetanib (Zactima)