Effect of Perampanel on Peritumoral Hyperexcitability in HGG

Inclusion Criteria:

* Participants must have radiologic evidence of anaplastic astrocytoma or glioblastoma multiforme within 14 days of enrollment.
* Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm (≥1 cm) with CT or MRI. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.
* Age ≥18 years.
* ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
* Participants must have adequate organ and marrow function as defined below:

  * absolute neutrophil count ≥1,500/mcL
  * platelets ≥100,000/mcL
  * total bilirubin ≤ institutional upper limit of normal (ULN)
  * AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
  * glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 (see Appendix B)
* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
* The effects of perampanel on the developing human fetus are unknown. For this reason and because some anti-seizure medications are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. 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.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Participants with brain metastases due to confounding effects on the study objectives.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to perampanel.
* Participants receiving any medications or substances that are moderate or strong inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
* Participants with uncontrolled intercurrent illness.
* Participants with psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant women are excluded from this study because perampanel is an anti-seizure agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with perampanel, breastfeeding should be discontinued if the mother is treated with perampanel.
* Participants with a history of suicide attempt or current active suicidal ideation with intent as defined by Columbia Suicide Severity Rating Scale (C-SSRS) type 4-5, due to the potential for suicidal ideation with the use of all anti-seizure medications.
* Participants who are unable to swallow pills.
* Participants with tumor associated seizures greater than one month before planned surgery.
* Participants currently receiving treatment with more than one anti-seizure medication.