Seizure Prophylaxis in Patients With Glioma or Brain Metastasis

NCT ID: NCT03436433

Last Updated: 2023-04-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-31
• Study Completion Date: 2020-12-04

Brief Summary

This protocol is designed to assess the need for seizure prophylaxis in the perioperative period for patients undergoing neurosurgical procedure (gross-total resection, sub-total resection or biopsy) for suspected diagnosis of new, recurrent or transformed glioma (WHO grade I-IV) and brain metastasis. This will be determined by observing the impact of Lacosamide (LCM), Levetiracetam (LEV), or no anti-epileptic drug (AED) on whether visits to the emergency department (ED) or hospital re-admissions occur within 30 days after procedure. A secondary endpoint will evaluate the safety and tolerability of LCM and LEV. Exploratory endpoints will evaluate admission duration for the procedure, number of post-operative provider communications (telephone, email, and additional clinic encounters, etc.), and patient risk factors associated with post-operative seizure.

Detailed Description

The protocol will assess the need for AED prophylaxis during the post-operative period in patients undergoing neurosurgical procedure for a suspected diagnosis of glioma (WHO grade I-IV) and brain metastasis. 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) and brain metastasis. The AED can be initiated anytime within 48 hours before neurosurgical procedure.

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 or brain metastasis, 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.

Conditions

Glioma; Glioma of Brain; Brain Tumor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lacosamide

Enrolled subjects will be randomized to receive Lacosamide.

Group Type: ACTIVE_COMPARATOR

Lacosamide

Intervention Type: DRUG

LCM 100mg twice a day.

Levetiracetam

Enrolled subjects will be randomized to receive Levetiracetam.

Group Type: ACTIVE_COMPARATOR

Levetiracetam

Intervention Type: DRUG

LEV 1000mg twice a day.

No anti-epileptic

Enrolled subjects will be randomized to not receive anti-epileptic drugs.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Lacosamide

LCM 100mg twice a day.

Intervention Type: DRUG

Levetiracetam

LEV 1000mg twice a day.

Intervention Type: DRUG

Other Intervention Names

LCM; Vimpat; LEV; Keppra

Eligibility Criteria

Inclusion Criteria

1. Patients with a suspected diagnosis of new, recurrent, or transformed glioma (WHO grade I-IV) or brain metastasis scheduled for neurosurgical procedure (gross-total resection, sub-total resection or biopsy) 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Annick Desjardins, M.D.

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Pro00081334

Identifier Type: -

Identifier Source: org_study_id