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

NCT05698524 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 0809-22-FB
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (3)

• Toxicities Associated with PCI-24781/Abexinostat and Metronomic Temozolomide Therapy - Adverse Events and Serious Adverse Events

  The incidence of adverse events (AEs) and serious adverse events (SAEs) will be recorded for each dose level cohort. Toxicities will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Toxicities will be graded on from 1 to 5, with higher numbers indicating a higher severity grade.

  Up to 25 months

• Toxicities Associated With PCI-24781/Abexinostat and Metronomic Temozolomide Therapy - Overall

  The frequency of overall toxicity occurrence will be categorized by toxicity grades using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Toxicities will be graded ranging from 1 to 5, with higher numbers indicating a higher severity grade.

  Up to 25 months

• Recommended Dose Determination of PCI-24781/Abexinostat

  Participants who either complete the first cycle of treatment or experience a dose-limiting toxicity (DLT) within the first cycle of treatment will be considered evaluable. The target DLT rate for the maximum tolerated dose (MTD) is 0.25. The MTD determination will be based on isotonic regression. The MTD will be defined as the dose for which the isotonic estimate of the DLT rate is closest to the target DLT rate of 0.25. If a tie exists between potential doses the higher dose level will be selected when the isotonic estimate is lower than the target DLT rate and the lower dose level will be selected when the isotonic estimate is greater than or equal to the target DLT rate. If the observed DLT rate at the current dose is ≤ 0.197, escalate the dose to the next higher dose level. If the observed DLT rate at the current dose is \> 0.298, de-escalate the dose to the next lower dose level. Otherwise, stay at the current dose level.

  Up to 20 months

Secondary Outcomes (8)

• Changes in Acetylation of Peripheral Blood Mononuclear Cell Histones, H3 and H4, During Treatment

  Up to 20 months

• Changes in Acetylation of Histones, H3 and H4, Using Peripheral Blood Exosomes

  Up to 20 months

• Progression-free Survival

  36 months

• Overall Survival (OS)

  36 months

• Descriptive examination of patient quality of life during treatment (EORTC QLQ-C30)

  24 months

Study Arms (1)

Single arm

EXPERIMENTAL

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.

Drug: PCI 24781; Drug: Temozolomide

Interventions

PCI 24781 DRUG

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

Also known as: Abexinostat

Single arm

Temozolomide DRUG

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

Also known as: Temodar

Single arm

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Nebraska: lead
• Xynomic Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

MeSH Terms

Conditions

Glioma; Astrocytoma; Oligodendroglioma; Glioblastoma; Gliosarcoma

Interventions

abexinostat; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nicole A Shonka, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michaela K Savine, RN

CONTACT

402-836-9488; misavine@unmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2022
• First Posted: January 26, 2023
• Study Start: June 26, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)