A Study of Temodar With Abexinostat (PCI-24781) for Patients With Recurrent Glioma

Prior treatment

• 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)
• 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)

Other illness

• 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
• 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)

Lab values

• 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
• 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

Other

• Pregnant or breast-feeding

• 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