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

Launched by UNIVERSITY OF NEBRASKA · Jan 24, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with recurrent glioma, a type of brain cancer that includes conditions like glioblastoma and anaplastic astrocytoma. It aims to find the best dose of a medication called Abexinostat, combined with a standard chemotherapy drug called temozolomide, to see how well they work together and to monitor any side effects. The trial is currently looking for participants who are 19 years or older and have had their glioma return after previous treatments, such as radiation and chemotherapy.

If you join this trial, you can expect to receive careful monitoring from the research team. You will need to provide consent after learning about the study, its potential benefits, and risks. There are specific health requirements to be eligible, such as having a certain level of blood cell counts and organ function. It's important to note that participants cannot be pregnant or breastfeeding, and those with certain medical conditions may not be eligible. This trial is an opportunity to contribute to research that could help improve treatment options for glioma in the future.

Gender

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Eligibility criteria

• 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)