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NOT YET RECRUITING
NCT07778602
EARLY_PHASE1

Safety and Feasibility of First-line Avutometinib and Defactinib in Patients With Newly Diagnosed High-grade Gliomas

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

View on ClinicalTrials.gov

Summary

This clinical trial is designed with two treatment stages: Stage 1: one cycle of study drug treatment prior to initiation of first-line standard radiation in all study participants. Stage 2: two additional cycles of study drug treatment (8 weeks total) concomitantly with standard of care radiation (\~6 weeks) for participants with pathology-confirmed MGMT (enzyme O-6-methylguanine-DNA methyltransferase) unmethylated GBM only. The co-primary endpoints of the study are 1) feasibility of completing Stage 1 of treatment prior to radiation in all study participants and starting radiation within 6 weeks, and 2) safety of study drug across both treatment parts. The investigators will additionally evaluate the radiographic response rate after the first cycle of drug in all patients based upon RANO 2.0 (Response Assessment in Neuro-Oncology) criteria as well as safety of study drug in all patients (secondary endpoints). Exploratory endpoints will include characterization of ERK (extracellular signal-regulated kinase) and FAK (Focal adhesion kinase) dependence in pre-treatment tissue (by immunohistochemistry and/or 'omics) and correlation of expression and co-mutations with response and survival. A total of up to 22 evaluable patients can be enrolled in this study. Evaluable patients are those who have received at least one dose of study drug treatment. Patients who do not start drug will be replaced, up to a total of 28 patients.

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

22

Start Date

2026-11-10

Completion Date

2029-12-23

Last Updated

2026-08-21

Healthy Volunteers

No

Interventions

DRUG

avutometinib and defactinib for 3 weeks on/1 week off

avutometinib 3.2 mg orally twice weekly and defactinib 200 mg orally twice a day for 3 weeks on/1 week off (one cycle = 4 weeks total)

DRUG

MGMT-unmethylated GBM with Radiation

Patients whose final pathology is MGMT promoter unmethylated GBM will receive an additional 2 cycles of avutometinib/defactinib concurrently with radiation (without temozolomide).

Locations (3)

Emory University

Atlanta, Georgia, United States

Johns Hopkins SKCCC

Baltimore, Maryland, United States

Universidad Central del Caribe

Bayamón, Puerto Rico