Recruiting
Phase 1

Temodar & Abexinostat

Sponsor:

University of Nebraska

Code:

NCT05698524

Conditions

Recurrent High Grade Glioma

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Glioblastoma

Gliosarcoma

Eligibility Criteria

Sex: All

Age: 19+

Healthy Volunteers: Not accepted

Interventions

PCI 24781

Temozolomide

Study Details

Brief summary:

Glioblastoma (GBM), WHO grade IV glioma, represents the majority of adult malignant primary brain tumors, with an incidence of 2-3 per 100,000 person-years. The survival for GBM has increased in the last decade but is still low with a median survival of 15-18 months. Recurrence after initial standard therapy, radiation therapy and chemotherapy with temozolomide, few options are available. Even with further therapy, median progression free survival at 6 months after first relapse (PFS-6) is only 15%. Similarly, anaplastic astrocytoma and anaplastic oligodendroglioma, grade III gliomas, once recurrent after radiation therapy and first-line chemotherapy, have identical therapeutic options and poor outcomes with PFS-6 of 31%. Temozolomide (TMZ) has a favorable side effect profile and is available orally, however, cytotoxicity occurs. Metronomic temozolomide at low doses on a continuous schedule, have demonstrated better survival in studies. This study will determine the recommended dose and the side effects of PCI-24781/Abexinostat with metronomic temozolomide.

Conditions

Recurrent High Grade Glioma

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Glioblastoma

Gliosarcoma

Study ID

NCT05698524

Start date

Jun 26, 2023

Status verified date

Sep, 2026

Completion date

Jul, 2027

Anticipated

Primary completion date

Jul, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 19+

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

24 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Single arm

Participants will receive a combination of PCI-24781/Abexinostat and temozolomide: loading dose of PCI-24781/Abexinostat prior to the start of Cycle 1, PCI-24781/Abexinostat by mouth twice a day starting 7 days prior to Cycle 1, Day 1 and ending 4 days prior to Cycle 1, Day 1.

Participants will continue taking PCI-24781/Abexinostat on days 1 - 4, 8 - 11, and 15 - 18 of each 28 day cycle, starting with Cycle 1, Day 1. The initial dose level is 60 mg of PCI-2478/Abexinostat by mouth twice daily. The dose level may be escalated based on results of interim data analysis.

Participants will additionally initiate metronomic temozolomide on Cycle 1, Day 1 at a dose of 50 mg/m2, taken by mouth twice daily and continue the PCI-24781/Abexinostat and metronomic temozolomide regimen until disease progression or intolerance.

Interventions

PCI 24781

Participants will take PCI-24781/Abexinostat on days 1 - 4, 8 - 11, and 15 - 18 of each 28-day cycle.

Temozolomide

Participants will receive temozolomide at a dose of 50 mg/mg2, taken by mouth once daily.

Primary outcome measure

  • Toxicities Associated with PCI-24781/Abexinostat and Metronomic Temozolomide Therapy - Adverse Events and Serious Adverse Events [ Time Frame: Up to 25 months ]
  • Toxicities Associated With PCI-24781/Abexinostat and Metronomic Temozolomide Therapy - Overall [ Time Frame: Up to 25 months ]
  • Recommended Dose Determination of PCI-24781/Abexinostat [ Time Frame: Up to 20 months ]

Central Contacts and Locations

Central contacts

Michaela K Savine, RN

402-836-9488misavine@unmc.edu

Locations

University of Nebraska Medical Center

Recruiting

Omaha, Nebraska, United States, 68198

Contacts

Michaela K Savine, RN

402-836-9488misavine@unmc.edu

More Information

Sponsor

University of Nebraska

Last update posted

Sep 14, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-25. This information was provided to ClinicalTrials.gov by University of Nebraska on 2026-09-14. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.