BTTC11-01: Randomized, double-blind, placebo-controlled trial of lacosamide for seizure prophylaxis in patients with High-Grade Gliomas

Study ID
STU 052012-067

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

Contact
Penny Currykosky
214-648-2926
penny.currykosky@utsouthwestern.edu

Principal Investigator
Edward Pan

Summary

There is no consensus among neurologists, neurosurgeons, and oncologists regarding the need for prophylactic antiepileptic drugs (aeDs) among newly-diagnosed and peri-operative high-grade gliomas (HGG) patients who have not experienced seizures. unfortunately, data regarding prophylactic aeD use is scant and inconclusive. Most of the available evidence comes from older, small studies that enrolled patients with brain metastases and benign tumors in addition to gliomas. Furthermore, these studies universally evaluated prophylaxis with first-generation aeDs such as phenytoin, phenobarbital, carbamazepine, and valproic acid. These drugs have high rates of adverse effects compared to newer aeDs, and they have important interactions with other drugs including corticosteroids and chemotherapeutics. Recently developed aeDs such as lacosamide are effective, safe, and well-tolerated. Lacosamide has no known drug interactions and does not require serum level monitoring. Despite limited published data, in many neuro-oncology centers newer aeDs such as levetiracetam, pregabalin, and lacosamide are emerging as the drugs of choice for seizure prophylaxis. a definitive clinical trial is needed to determine whether prophylactic aeD therapy may reduce the risk of first seizures in this patient population. in addition, evaluation of the impact of newer generation aeDs is needed to provide support to the use in this patient population.

Randomization:
The patients will be stratified based on use or non-use of peri-operative anti-epileptic drugs and by institution.

Study procedures:
The starting dose of lacosamide or placebo will be 50 mg Po bid. over 4 weeks, the dose should be increased to a target dose of 200 mg bid. a recommended scheme for dose escalation is to increase by 100 mg/day weekly until 200 mg bid is achieved. Deviations from this scheme that achieve a dose of 200 mg bid by 4 weeks will not be considered protocol violations.

The labels on the bottles will have a bottle number and dose strength. Bottles will be labeled either 50mg or 100mg. So the patient will know what strength of drug/placebo is in the bottle and they will know the bottle number. no one except uVi (the distributor), the MD anderson information Services personnel that maintains the randomization database, and the protocol biostatistician knows which bottles are drug and which are placebo.

The study drug will be dispensed in 2 blinded bottles, labeled 50mg and 100mg. The uTSW staff (physicians, nurses, and pharmacist) will remain blinded and will increase the dose as normal (placebo or Lacosamide). The patient will follow a schedule similar to below:
Week 1 [?] 50mg BiD
Week 2 [?] 100mg BiD
Week 3 [?] 150mg BiD
Week 4 [?] 200mg BiD
Please note: the patients will be taking additional anti seizure medication. Standard of care is to prescribe Lacosamide along with another anti seizure drug such as Keppra.


use of placebo in this trial is to determine if the use of aeDs post-operative reduces the incidence or onset of seizures in patients newly diagnosed with high-grade glioma (HGG).

Participant Eligibility

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 be > or equal to 18 years old.

Patients must have a Karnofsky performance status of > or equal to 60.

Women of childbearing potential must have a negative [BETA]-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.