A Study of Temodar With Abexinostat (PCI-24781) for Patients With Recurrent 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 previousprogressions are eligible (prior bevacizumab and Optune are allowed)

• Three or more months from the end of chemoradiotherapy or have biopsy or imagingconsistent 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 theinvestigator, 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, plateletcount ≥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 ofnormal, 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 daysof initiating study (non-child bearing potential is defined as age 55 years or olderand no menses for two years or any age with surgical removal of the uterus and/orboth ovaries)

• Females of reproductive potential must agree to employ an effective barrier methodof 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 withthe absorption or metabolism of oral PCI-24781/Abexinostat, or put the studyoutcomes at undue risk

• Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmia,congestive heart failure, or myocardial infarction within 6 months of screening, orany Class 3 or 4 cardiac disease as defined by the New York Heart AssociationFunctional Classification

• Malabsorption syndrome, disease significantly affecting gastrointestinal function,or resection of the stomach or small bowel or ulcerative colitis, symptomaticinflammatory bowel disease, or partial or complete bowel obstruction

• Immunotherapy, chemotherapy, radiotherapy, corticosteroids (at dosages equivalent toprednisone > 20 mg/day) or experimental therapy (other than PCI-24781/AbexinostatPO) 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 controlledprostate cancer

• Known history of Human Immunodeficiency Virus (HIV) or active infection withHepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled activesystemic infection (no testing is required for eligibility)

• Creatinine > 1.5 x institutional upper limit of normal (ULN); total bilirubin > 1.5x ULN (unless from Gilbert's disease), and aspartate aminotransferase (AST) oralanine 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 treatmentor 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)