Lacosamide in Preventing Seizures in Participants With Malignant Glioma

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.