This trial studies how well lacosamide works in preventing seizures in participants with malignant glioma. Anti-seizure drugs, such as lacosamide, may decrease abnormal electrical activity in the brain that plays a role in developing seizures.

PRIMARY OBJECTIVES:

I. To determine if prophylactic administration of Lacosamide reduces the risk of seizures in patients with high-grade glioma (HGG).

SECONDARY OBJECTIVES:

I. To determine the one-year risk of first seizure in this patient population. II. To evaluate patient reported symptoms.

EXPLORATORY OBJECTIVES:

I. To investigate clinical and electroencephalographic predictors of seizures in this patient population.

II. To evaluate the occurrence of symptoms and correlate to seizure activity as well as tolerance to treatment using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) self-reporting tool.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I (LACOSAMIDE): Participants receive lacosamide orally (PO) twice a day (BID) for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.

ARM II (PLACEBO): Participants receive a placebo PO BID for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up every 3 months for 5 years.

Inclusion Criteria:

• Patients with histologically confirmed supratentorial high-grade glioma will be eligible for this protocol.
• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
• Patients must have signed an authorization for the release of their protected health information.
• Patients must have a Karnofsky performance status of >= 60.
• Women of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test documented within 2 weeks prior to registration.
• In the opinion of the treating investigator, patients must have adequate cognitive abilities to complete the neurocognitive components of the study.
• Patients must be able to safely swallow pills.
• Patients must agree to practice adequate contraception.
• Patients must be registered on study within 16 weeks after the surgical procedure that established the diagnosis of high grade glioma.

Exclusion Criteria:

• Patients must not have any significant medical or psychiatric illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
• Patients must not have serious intercurrent medical illness. Serious, active co-morbidity, defined as follows: a) Unstable angina and/or congestive heart failure requiring hospitalization within the last 12 months. b) Transmural myocardial infarction within the last 6 months. c) Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration. d) Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration. e) Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol. f) Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. g) Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity.
• Patients must not be pregnant or breast feeding. Patients must not be pregnant because lacosamide produced developmental toxicity in rats following administration during pregnancy. There is insufficient information to determine if lacosamide is safe during lactation.
• Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
• Patients must not have a history of heart block or cardiac arrhythmia, including asymptomatic arrhythmias and atrial fibrillation/flutter.
• Patients must not have a prolonged PR interval (defined as > 200 ms).
• Perioperative anticonvulsants should be tapered as indicated in the protocol.
• Patients must not have a history of any type of seizure for at least 10 years prior to registration.

Adverse event data collected for up to one year treatment period.

This is a cooperative group protocol. It was not an MDACC protocol. BTTC was administratively located at MDACC. The main PI/Academic PI was located at an outside institution.