Lacosamide in Preventing Seizures in Participants With Malignant Glioma

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

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.

Study Overview

• Status: Terminated
• Conditions: Malignant Glioma
• Intervention / Treatment: Other: Placebo; Drug: Lacosamide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (lacosamide); Participants receive lacosamide PO BID for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.	Drug: Lacosamide; Given PO; Other Names: ADD 234037; Erlosamide; Harkoseride; SPM 927; Vimpat
Placebo Comparator: 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.	Other: Placebo; Given PO; Other Names: placebo therapy; PLCB; sham therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Seizures	Number of Participants that had seizure in a randomized, two-arm, parallel groups of post-operative participants with newly-diagnosed high-grade glioma (HGG)	12 months or first seizure

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Marta Penas-Prado, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2012
• Primary Completion (Actual): June 20, 2017
• Study Completion (Actual): June 20, 2017

Study Registration Dates

• First Submitted: September 8, 2011
• First Submitted That Met QC Criteria: September 9, 2011
• First Posted (Estimate): September 12, 2011

Study Record Updates

• Last Update Posted (Actual): December 19, 2018
• Last Update Submitted That Met QC Criteria: November 27, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neurologic Manifestations; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Seizures; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lacosamide
• Other Study ID Numbers: BTTC11-01 (Other Identifier: M D Anderson Cancer Center); P30CA016672 (U.S. NIH Grant/Contract); NCI-2018-01854 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No