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.
Patient must be able to provide written informed consent.
≥ 18 years of age
Likely high-grade glioma based on frozen pathology in patients with no prior diagnosis of a glioma or astrocytoma.
Patient appropriate for standard therapy for high-grade glioma that includes 6 weeks of radiation.
Any prior glioma or astrocytoma, or any prior cancer diagnosis resulting in irradiation of the skull or scalp
Significant bi-hemispheric disease or midline shift observed on post-operative MRI likely to result in rapid clinical deterioration
Those who have undergone diagnostic biopsy only for suspected primary brain cancer.
Those who are on other investigational agents at the time of screening and including patients on carmustine and/or gamma tiles
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Lead sponsor
Keep Punching Foundation
Collaborator