PRIMARY OBJECTIVES:~I. To estimate the recommended phase 2 dose (RP2D) of trametinib given orally in combination with everolimus in pediatric and young adult patients with gliomas.~II. To describe the toxicity profile and define the dose limiting toxicities (DLTs) of the combination of trametinib and everolimus in pediatric and young adult patients with recurrent low-grade gliomas (LGG) or high grade glioma (HGG).~III. To characterize the pharmacokinetic profile of trametinib and everolimus when given in combination.~EXPLORATORY OBJECTIVES:~I. To describe the objective response rate and the 2-year progression-free survival (PFS) of LGGs to this therapy in the context of a phase I study.~II. To assess quality of life (QOL) and cognitive measures in pediatric and young adult patients with LGG or HGG.~III. To identify potential predictive biomarkers to targeted therapy in pediatric and young adult patients with LGGs.~IV. To assess endocrine outcomes in pediatric and young adult patients with LGGs.~V. To explore magnetic resonance (MR) quantitative measures of relative cerebral blood volume, permeability and apparent diffusion coefficient within the region of hyperintensity on T2-weighted images as markers of disease response and/or progression in comparison to institutional evaluation of disease response and/or progression and quantitative measures of tumor response as determined by central review (based upon both area and volumetric measures).~OUTLINE: This is a dose-escalation study.~Patients receive a combination of trametinib orally (PO) and everolimus in either of two dosing scheduled (continuous and intermittent). Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, then every 6 months for 5 years from the start of therapy.
This phase I trial studies the side effects and best dose of trametinib and everolimus in treating pediatric and young adult patients with gliomas that have come back (recurrent). Trametinib acts by targeting a protein in cells called MEK and disrupting tumor growth. Everolimus is a drug that may block another pathway in tumor cells that can help tumors grow. Giving trametinib and everolimus may work better to treat low and high grade gliomas compared to trametinib or everolimus alone.