PRIMARY OBJECTIVES:~I. To confirm penetration of fimepinostat across the blood brain barrier (BBB) in children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG), recurrent medulloblastoma, or recurrent high-grade glioma (HGG) by measuring concentration of fimepinostat and metabolite in primary tumor tissue.~EXPLORATORY OBJECTIVES:~I. To assess pharmacokinetics (PK) of fimepinostat in plasma and tumor tissue of children and young adults with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG.~II. To assess pharmacodynamics (PD) of fimepinostat in children and young adults with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG as measured by phosphorylation and acetylation in tumor tissue.~III. To correlate acetylation and phosphorylation in tumor tissue with tissue and plasma PK levels.~IV. To assess the safety and tolerability of fimepinostat in children and young adults with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG.~V. To assess preliminary efficacy of fimepinostat given as monotherapy after surgery in children and young adults with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG, as based on progression-free survival (PFS) and objective response rate (ORR) as appropriate.~OUTLINE:~Patients receive fimepinostat orally (PO) once daily (QD) on days -2 to 0. Within 2 hours of receiving fimepinostat on day 0, patients undergo tumor resection.~MAINTENANCE PHASE: Patients receive fimepinostat by mouth, once daily for days 1-5 each week. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 12 months from the time treatment begins. Should patients continue to derive clinical benefit, and not experience excess toxicity or progression, patients can continue to receive drug for up to 24 months or longer pending discussion with study chairs and study sponsor.~After completion of study treatment, patients are followed up at 30 days, then every 3 months for up to 5 years.
This trial studies how well fimepinostat works in treating patients with newly diagnosed diffuse intrinsic pontine glioma, or medulloblastoma, or high-grade glioma that have come back. Fimepinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.