Phase II Trial of Seizure Prophylaxis in Suspected Primary Glioma Patients Undergoing Craniotomy

The protocol will assess the need for AED prophylaxis during the post-operative period in
patients undergoing craniotomy for a suspected diagnosis of glioma (WHO grade I-IV). Patients
(n=116) will be consented and randomized at their pre-operative assessment, either at their
pre-operative clinic visit or in the ED, if that is the time of their initial presentation
prior to surgery. There will be three arms to the study - patients will be randomized to LCM,
LEV, or control (no AED). Randomization will be stratified by suspected grade (LGG vs HGG).
The AED can be initiated anytime within 48 hours before a craniotomy incision.

Doses will be either LCM 100mg twice a day (BID) (Arm A), LEV 1000mg BID (Arm B), or no AED
(Arm C). If a patient is randomized to Arm C and undergoes tumor mapping, the patient is
allowed to receive one dose of AED in the operating room. If a patient is randomized to Arm A
or Arm B and takes the morning dose of their AED, they do not need an intra-operative dose of
AED. If a patient has a seizure during the post-operative period, AEDs will be adjusted at
the discretion of the treating physician. However, if a patient has intolerable side effects,
patients will be changed to a different dose of the same medicine before consideration of
another AED [i.e., BID to four times a day (QID) dosing if patient experiences diplopia on
LCM].

Patients with high-grade tumors (newly-diagnosed or transformed) will be treated with
standard radiation and temozolomide therapy per the Stupp protocol 25,70. For these patients,
an AED taper will be initiated at the first clinic visit after completion of radiation. For
patients with a low-grade tumor or recurrent disease of any grade, an AED taper will be
initiated at the first scheduled post-operative visit, approximately 6-10 weeks after the
operation. LCM will be tapered by 100mg a week one week at a time. LEV will be tapered
500-1000mg one week at a time.

Inclusion Criteria:

1. Patients with a suspected diagnosis of new, recurrent, or transformed glioma (WHO
grade I-IV) scheduled for craniotomy at Duke University Medical Center (DUMC);

2. Safe for surgery per treating neurosurgeon;

3. Due to the potential implications of the treatment on the developing central nervous
system (CNS), all patients must be ≥ 18 years of age at the time of entry into the
study;

4. Laboratory Studies:

1. Total bilirubin, Serum Glutamic Oxaloacetic Transaminase (SGOT), Serum Glutamic
Pyruvic Transaminase (SGPT), Alkaline Phosphatase (ALK) ≤ 1.5 x upper limit of
normal (ULN)

2. Creatinine ≤ 1.5

5. A signed informed consent form approved by the Duke University Institutional Review
Board (IRB) will be required for patient enrollment into the study. Patients must be
able to read and understand the informed consent document and must sign the informed
consent indicating that they are aware of the investigational nature of this study.

6. Patients of child bearing potential or with partners of child-bearing potential must
agree to practice recommended contraceptive methods to prevent pregnancy during
treatment and for 1 month after the last dose of AED for women and men.

Exclusion Criteria:

1. Pregnant or need to breast feed during the study period (Negative urine β-human
chorionic gonadotropin (HCG) test required), or unable to maintain use of
contraception while on study and for 1 month after the last dose of AED;

2. Patients already on AED(s);

3. Known history of epilepsy/seizure disorder;

4. Known history of dependency/abuse of psychopharmaceuticals, alcohol, illicit drugs or
narcotics;

5. Any significant medical or psychiatric illness that cannot be adequately controlled
with appropriate therapy or would compromise the patient's ability to tolerate
therapy, per the discretion of the treating investigator;

6. Known allergy to LCM or LEV.