Fimepinostat in Treating Brain Tumors in Children and Young Adults

Inclusion Criteria:

* Patients must have one of the following histologically confirmed diagnoses (histologic confirmation from initial diagnosis acceptable, as appropriate):

  * Stratum A: Newly diagnosed diffuse intrinsic pontine glioma (WHO grade II-IV) - this stratum does not require tissue confirmation at time of enrollment, but diagnostic confirmation will be required to continue on study after biopsy. Patients with newly diagnosed DIPG will be eligible to enroll before or after standard of care radiation, but must be eligible for a biopsy. Newly diagnosed DIPG stratum should not have received prior therapy before the initiation of fimepinostat, with the exception of those patients who received temozolomide during radiation therapy or who previously received radiation as per standard of care and have not yet undergone a biopsy. All patients who have received therapy other than radiation and temozolomide should be discussed with study chair(s) prior to enrollment. Patients enrolling after standard of care radiation must be enrolled within 14 weeks of completion of radiotherapy.
  * Stratum B: Recurrent medulloblastoma (WHO grade IV), any molecular subtype
  * Stratum C: Recurrent high-grade glioma (HGG), including anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV)

    * Stratum B \& C: Patients in the recurrent medulloblastoma or recurrent HGG arm can have locally recurrent or disseminated disease, provided resection/biopsy would still be clinically indicated. Disseminated disease can be diagnosed by imaging or Cerebrospinal fluid (CSF) cytology. Recurrent DIPG will be eligible for stratum C; however, eligibility requires biopsy/resection is feasible in a region of tumor outside of the pons (i.e. cerebellar extension or new metastatic site). These patients should be discussed with study chair(s) prior to enrollment
* Patients must be able to swallow intact fimepinostat capsules or mini-tabs without chewing or crushing
* Patients must have body surface area (BSA) \>= 0.5 m\^2
* Patients must undergo tumor tissue collection as part of their standard of care

  * Minimum possible tissue collected must be equivalent to about 4-6 stereotactic core biopsies
* Prior Therapy: Patients in the medulloblastoma and HGG strata will be allowed to have undergone prior therapy including surgery, chemotherapy, and radiation therapy. Patients in the newly diagnosed DIPG stratum should not have received prior therapy before the initiation of fimepinostat, with the exception of those patients who received temozolomide during radiation therapy or who previously received radiation as per standard of care and have not yet undergone a biopsy. All patients who have received therapy other than radiation and temozolomide should be discussed with study chair(s) prior to enrollment. Patients must have fully recovered from acute side effects related to previous anti-cancer therapies. Patients undergoing radiation during protocol therapy will not be permitted to receive other concomitant agents with radiation and pending initiation of maintenance with fimepinostat

  * Myelosuppressive chemotherapy: At least 21 days after last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
  * Hematopoietic growth factors: At least 14 days after last dose of a long-acting growth factor or 7 days after short-acting growth factor or beyond time during which adverse events are known to occur
  * Biologic (anti-neoplastic agent): At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur
  * Monoclonal antibodies: At least 21 days after last dose of monoclonal antibody
  * Radiotherapy:

    * At least 2 weeks after local palliative radiotherapy (XRT)
    * At least 3 months from craniospinal XRT, or XRT to \> 50% pelvis
  * Surgery:

    * At least 21 days from major surgery (biopsy and central line placement/removal are not considered major)
* Corticosteroids: Subjects who are receiving dexamethasone must be on a stable or decreasing dose for at least 7 days prior to enrollment
* Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3
* Platelet count \>= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 milliliters (mL)/minute (min)/1.73 m\^2 or
* A serum creatinine based on age/gender as follows:

  * Age: Maximum Serum Creatinine (mg/dL)
  * 3 to \< 6 years: 0.8 (male), 0.8 (female)
  * 6 to \< 10 years: 1 (male), 1 (female)
  * 10 to \< 13 years: 1.2 (male), 1.2 (female)
  * 13 to \< 16 years: 1.5 (male), 1.4 (female)
  * \>= 16 years: 1.7 (male), 1.4 (female)
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) =\< 110 U/L
* Serum albumin \>= 2 g/dL
* Neurologic function:

  * Subjects with seizure disorder may be enrolled if well controlled
* Gastrointestinal function:

  * Diarrhea \< grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0
* Metabolic function:

  * Non-fasting glucose \< 125 mg/dL without the use of antihyperglycemic agents

    * If non-fasting glucose \> 125 mg/dL, a fasting glucose should be done. If fasting glucose =\< 160 mg/dL without the use of antihyperglycemic agents, patient will meet adequate metabolic function criteria
* Cardiac function: corrected QT (QTc) \< 480 msec
* The effects of fimepinostat on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 30 days after completion of fimepinostat administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate

Exclusion Criteria:

* Subjects who have not recovered from acute adverse events due to therapeutic agents administered more than 4 weeks earlier
* Patients must not have received prior therapy with single-agent or combination histone deacetylase (HDAC) and Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) inhibitors
* Subjects who are receiving any other investigational agent
* History of allergic reaction to compounds of similar chemical or biological composition to fimepinostat
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
* Patients with active human immunodeficiency virus (HIV) infection and with potential life-threatening consequences associated with immune-suppressive therapy
* Patients with history of type 1 or 2 diabetes mellitus
* Patients with gastrointestinal condition that could interfere with absorption or metabolism of fimepinostat