Seizure Prophylaxis Study

• ClinicalTrials.gov Identifier: NCT03436433
• Recruitment Status: Recruiting
• First Posted: February 16, 2018
• Last Update Posted: September 19, 2019
• Sponsor: Duke University
• Information provided by (Responsible Party): Duke University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Glioma; Glioma of Brain; Brain Tumor	Drug: Lacosamide; Drug: Levetiracetam	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 232 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Upon consent, patients will be randomized in REDCap™ to receive either LCM, LEV, or no AED. Randomization will be stratified by suspected histologic grade (LGG vs HGG vs brain metastasis) based on MRI review by the treating neurosurgeon and/or neuro-oncologist. A stratified permuted block randomization algorithm will be used assign patients to treatment arms.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Seizure Prophylaxis in Brain Tumor Patients Undergoing Neurosurgical Procedure
• Actual Study Start Date: January 31, 2019
• Estimated Primary Completion Date: January 31, 2021
• Estimated Study Completion Date: January 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Lacosamide; Enrolled subjects will be randomized to receive Lacosamide.	Drug: Lacosamide; LCM 100mg twice a day.; Other Names: LCM; Vimpat
Active Comparator: Levetiracetam; Enrolled subjects will be randomized to receive Levetiracetam.	Drug: Levetiracetam; LEV 1000mg twice a day.; Other Names: LEV; Keppra
No Intervention: No anti-epileptic; Enrolled subjects will be randomized to not receive anti-epileptic drugs.

Outcome Measures

Primary Outcome Measures :

1. Percentage of patients with an ED visit/hospital readmission within 30 days of craniotomy [ Time Frame: 30 days following surgery ]
   The primary objective of this study is to assess the impact of LCM, LEV or, no AED in patients undergoing craniotomy for suspected new, recurrent or transformed glioma (WHO Gr I-IV) or brain metastasis.

Secondary Outcome Measures :

1. Adverse event within first 30 days after craniotomy [ Time Frame: 30 days following surgery ]
   Adverse events related to LCM and LEV.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Claudia Pamanes; 919-668-0897; claudia.pamanes@duke.edu

Contact: Alexia Bwensa; 919-681-5484; alexia.bwensa@duke.edu

Locations

United States, North Carolina

Duke Comprehensive Cancer Center; Recruiting

Durham, North Carolina, United States, 27710

Contact: Clinical Trials Office - Duke Comprehensive Cancer Center 888-275-3853

Sponsors and Collaborators

Duke University

Investigators

• Principal Investigator: Annick Desjardins, M.D.; Duke University

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03436433 History of Changes
• Other Study ID Numbers: Pro00081334
• First Posted: February 16, 2018
• Last Update Posted: September 19, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Duke University:

anti-epileptic drugs; seizure prophylaxis; levetiracetam

Additional relevant MeSH terms:

Glioma; Brain Neoplasms; Seizures; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Lacosamide; Levetiracetam; Anticonvulsants; Nootropic Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action