Efficacy of Mirdametinib Alone or Combination With Radiotherapy for Germline and Sporadic NF1-Altered High-Grade Glioma
University of Alabama at Birmingham
Summary
This is a phase 2, open label, parallel multi-arm study of mirdametinib in combination with radiation in participants with recurrent sporadic glioblastoma (GBM) harboring NF1 alterations (Cohort 1); participants with NF1 with a newly diagnosed GBM (Cohort 2); mirdametinib alone in other NF1-associated High-Grade Gliomas (Cohort 3).
Description
Cohorts 1 and 2: Eligible participants will receive radiotherapy concurrently with twice daily mirdametinib. Mirdametinib will continue after completion of radiation in continuous 28-day cycles with treatment lasting up to 24 cycles. MR imaging to assess response will be performed 4 weeks after completion of radiation therapy, and every 2 months thereafter using Response Assessment in Neuro-Oncology (RANO) 2.0 enhancing criteria. Cohort 3: Eligible participants will receive twice-daily mirdametinib in 28-day cycles for 6 cycles. MR imaging to assess response by Response Assessment in Neuro-On…
Eligibility
- Age range
- 12–89 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Tumor diagnosis: * Cohort 1 (applies to non-NF1 related GBM): GBM, IDH-wildtype grade 4 of brain or spinal cord by WHO 2021 central nervous system tumor diagnostic criteria52 that is recurrent after irradiation and first-line chemotherapy (if appropriate). Any number of prior recurrences is acceptable. Tumor Next Generation Sequencing (NGS) must demonstrate at least one pathogenic/likely pathogenic NF1 alteration (known or suspected to confer loss of function) at time of first or recurrent surgery that could putatively confer loss-of-function. * Cohort 2 (applies to…
Interventions
- Combination Productmirdametinib with radiation
Participants in Cohorts 1 and 2 will receive mirdametinib in combination with radiation therapy followed by mirdametinib alone.
- Drugmirdametinib
Participants in Cohort 3 will receive mirdametinib alone.
Location
- Childrens of AlabamaBirmingham, Alabama