Combining Temozolomide with Abexinostat for Recurrent Glioma Treatment

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

This study is testing a new combination of two drugs, Temozolomide and Abexinostat, to see if it can help people with recurrent high-grade gliomas like glioblastoma feel better and manage their condition.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: University of Nebraska (Academic / other)
• Drugs / interventions: bevacizumab, chemotherapy, Immunotherapy, radiation, prednisone
• Locations: 1 site (Omaha, Nebraska)
• Trial ID: NCT05698524 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the combination of Temozolomide and Abexinostat (PCI-24781) for patients with recurrent high-grade gliomas, including glioblastoma and anaplastic astrocytoma. Participants will be assigned to different dose levels of Abexinostat, with dose adjustments based on observed toxicities during the initial treatment cycle. The study aims to determine the optimal dosing regimen while monitoring for safety and efficacy. The treatment will continue until disease progression or intolerable side effects occur.

Who should consider this trial

Good fit: Ideal candidates are adults aged 19 and older with a confirmed diagnosis of recurrent high-grade glioma who have previously undergone standard treatments.

Not a fit: Patients with low-grade gliomas or those who have not received prior radiation or chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve survival rates and quality of life for patients with recurrent gliomas.

How similar studies have performed: Previous studies have shown promise in using metronomic dosing of Temozolomide, suggesting potential for success with this combined approach.

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)

Where this trial is running

Omaha, Nebraska

• University of Nebraska Medical Center — Omaha, Nebraska, United States (Recruiting)

Study contacts

• Principal investigator: Nicole A Shonka, MD — University of Nebraska
• Study coordinator: Michaela K Savine, RN

Conditions Recurrent High Grade Glioma; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Glioblastoma; Gliosarcoma