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RecruitingNCT05698524

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

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

Status
Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
24 (estimated)
Sponsor
University of Nebraska · Academic / Other
Sex
All
Age
19 Years
Healthy volunteers
Not accepted

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.

Detailed description

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. Participants will be enrolled to one of each of four dose levels in cohorts of 3. Dose level escalation/de-escalation will follow Bayesian Optimal Interval (BOIN) design rules based on analysis of dose-limiting toxicities (DLTs) that occur within the first cycle of protocol treatment. Protocol treatment will continue until disease progression or intolerable toxicity. Dose Levels: 1 - 60 mg PCI-24781/Abexinostat two times daily (BID), 1.5 - 80 mg PCI-24781/Abexinostat BID, 2 - 100 mg PCI-24781/Abexinostat BID, and 3 - 140 mg PCI-24781/Abexinostat BID. The primary study objective is to evaluate the toxicities and determine the recommended dose of PCI-24781/Abexinostat with metronomic temozolomide in participants with recurrent high grade glioma, \[grade III or IV glioma (glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma)\]. Other objects are to evaluate changes in the acetylation of peripheral blood mononuclear cell (PBMC) histones H3 and H4 during treatment, evaluate acetylation of histones H3 and H4 using peripheral blood exosomes, evaluate progression-free and overall survival of participants with recurrent high grade glioma treated with therapy with PCI-24781/Abexinostat and metronomic temozolomide, descriptively examine quality of life (QOL) using EORTC QLQ-C30 questionnaire and QLQ-BN20 questionnaire during treatment, characterize the pharmacokinetics (PK) of PCI-24781/Abexinostat, temozolomide, and the combination of the 2 drugs, measure tumor response, and correlate molecular profiles with tumor response.

Conditions

Interventions

TypeNameDescription
DRUGPCI 24781Participants will take PCI-24781/Abexinostat on days 1 - 4, 8 - 11, and 15 - 18 of each 28-day cycle.
DRUGTemozolomideParticipants will receive temozolomide at a dose of 50 mg/mg2, taken by mouth once daily.

Timeline

Start date
2023-06-26
Primary completion
2027-07-01
Completion
2029-07-01
First posted
2023-01-26
Last updated
2026-04-17

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT05698524. Inclusion in this directory is not an endorsement.