Lacosamide for Seizure Prophylaxis in High-Grade Gliomas

Study ID
BTTC11-01

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital

Contact
Jennifer Hawkins
817/307-4408
jennifer.hawkins@utsouthwestern.edu

Principal Investigator
Edward Pan

Official Title

Randomized, Double-Blind, Placebo-Controlled Trial of Lacosamide for Seizure Prophylaxis in Patients With High-Grade Gliomas

Brief Overview


The goal of this clinical research study is to learn if an antiepileptic (anti-seizure)
treatment will prevent seizures in patients with brain tumors who have not yet had a
seizure. Anti-seizure drugs are designed to decrease abnormal electrical activity in the
brain that plays a role in developing seizures.

In this study, lacosamide will be used as an anti-seizure medication. Lacosamide will be
compared to a placebo.

A placebo is not a drug. It looks like the study drug but is not designed to treat any
disease or illness. It is designed to be compared with a study drug to learn if the study
drug has any real effect.

Summary


Study Drug Administration:

If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the flip of a coin) to receive either lacosamide or a placebo. Neither you nor your
doctor will know if you are receiving the study drug or placebo. However, if needed for
your safety during the study, the study staff and study doctor will be able to find out what
you are receiving.

You will take lacosamide or placebo by mouth 2 times a day, at about the same times each
day, spaced as close to 12 hours apart as possible. The study drug/placebo may be taken
with or without food. Missed doses should be only taken within 6 hours of the scheduled
time.

If you vomit while taking the study drug/placebo, you should not take more pills before the
next scheduled dose unless the pill can be clearly identified in the vomit.

You will be given a drug diary to fill out each day that you take the study pills. The
study staff will explain how to fill out this diary.

Study Visits:

Every month:

° You will be called and asked questions about any side effects you may be having. and
about your mood.

At Months 1, 4, 7, and 10:

- Your medical history will be recorded, including any drugs you may have taken and/or
may be taking.

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- You will have a neurological exam.

- At Months 4, 7, and 10, you will be asked about any side effects you may be having.

At any time during the study, extra tests may be performed if the doctor thinks they are
needed for your safety. The study doctor will tell you more about any extra tests.

Length of Study:

You may take lacosamide or placebo for up to 1 year. Your study doctor may take you off the
study early if he or she feels it is not in your best interest, you have new health problems
that make taking part in the study possibly dangerous, if intolerable side effects occur, or
if you are unable to follow study directions.

You will be considered off-study once you complete the Long-Term Follow-Up.

End-of-Dosing Visit:

After you stopped taking the study drug/placebo, you will have an end-of-dosing visit. At
this visit, the following tests and procedures will be performed:

- Your medical history will be recorded, including any drugs you may have taken and/or
may be taking and any side effects you may be having.

- You will complete the questionnaire about your mood.

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- You will have a neurological exam.

Long-Term Follow-Up:

Every 3 months after your End-of-Study visit, for about 5 years, you may be called and asked
how you are feeling if you do not schedule a required monthly follow up visit. This phone
call will take about 5-10 minutes.

This is an investigational study. Lacosamide is FDA approved and commercially available
for the treatment of seizures. Its use to reduce the risk of seizures in patients with
malignant gliomas is investigational.

Up to 302 patients will take part in this multicenter study. Up to 60 will be enrolled at
MD Anderson.

Participant Eligibility


Inclusion Criteria:

1. Patients with histologically confirmed supratentorial high-grade glioma will be
eligible for this protocol.

2. All patients must sign an informed consent indicating that they are aware of the
investigational nature of this study.

3. Patients must have signed an authorization for the release of their protected health
information.

4. Patients must be >/= 18 years old.

5. Patients must have a Karnofsky performance status of >/= 60.

6. Women of childbearing potential must have a negative beta-HCG pregnancy test
documented within 2 weeks prior to registration.

7. In the opinion of the treating investigator, patients must have adequate cognitive
abilities to complete the neurocognitive components of the study.

8. Patients must be able to safely swallow pills.

9. Patients must agree to practice adequate contraception.

10. Patients must be registered on study within 16 weeks after the surgical procedure
that established the diagnosis of High Grade Glioma.

Exclusion Criteria:

1. 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.

2. 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.

3. (2. continued) f) Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC
definition; note, however, that 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.

4. 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.

5. Patients must not have any disease that will obscure toxicity or dangerously alter
Drug metabolism

6. Patients must not have a history of heart block or cardiac arrhythmia, including
asymptomatic arrhythmias and atrial fibrillation/flutter.

7. Patients must not have a prolonged PR interval (defined as > 200 ms).

8. Perioperative anticonvulsants should be tapered as indicated in the protocol.

9. Patients must not have a history of any type of seizure for at least 10 years prior
to registration.