Perampanel for the Reduction of Seizure Frequency in Patients With High-grade Glioma and Focal Epilepsy

Sponsor

Mayo Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT04650204

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

32.5

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase IV trial studies the side effects and how well perampanel works in reducing seizure frequency in patients with high-grade glioma and focal epilepsy. Perampanel is a drug used to treat seizures. Giving perampanel together with other anti-seizure drugs may work better in reducing seizure frequency in patients with high-grade glioma and focal epilepsy compared to alternate anti-seizure drugs alone.

Condition or Disease	Intervention/Treatment	Phase
Intractable Epilepsy Malignant Glioma Seizure Disorder	Drug: Anticonvulsant Agent Drug: Perampanel Other: Quality-of-Life Assessment Other: Questionnaire Administration	Phase 4

Detailed Description

PRIMARY OBJECTIVE:

Demonstrate the efficacy and safety of perampanel (PER) on seizure frequency in adult patients with biopsy-proven high-grade glioma and focal epilepsy compared with alternate anti-seizure drugs (ASDs).

SECONDARY OBJECTIVES:

To assess the change in neurocognitive function and brain magnetic resonance imaging (MRI) progression over the course of PER treatment with a daily dose of 4 mg (up to -8mg) in patients with biopsy-proven high-grade glioma and focal epilepsy compared with alternate ASDs.
To identify a biomarker-specific response to seizure-reduction in patients treated with PER in patients with a biopsy-proven high-grade glioma (i.e., IDH-mutant versus [vs] wildtype).

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP A: Patients receive perampanel orally (PO) once daily (QD) 40 weeks in the absence of disease progression or unacceptable toxicity.

GROUP B: Patients receive ASD per standard of care for 40 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 12 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Phase IV, Prospective, Open-Label, Parallel Study Evaluating the Effect of an Adjunctive Anti-Seizure Medication Using a Glutamatergic Modulator in Patients With Focal Epilepsy and High-Grade Glioma

Actual Study Start Date :

Apr 30, 2020

Anticipated Primary Completion Date :

Jan 15, 2022

Anticipated Study Completion Date :

Jan 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (perampanel) Patients receive perampanel PO daily 40 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Perampanel Given PO Other Names: E2007 Fycompa Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies
Active Comparator: Arm B (ASD) Patients receive ASD per standard of care for 40 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Anticonvulsant Agent Given ASD Other Names: Anti-seizure agent anticonvulsant Anticonvulsant Agents Anticonvulsants antiepileptic Antiepileptic Agent Antiepileptics Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies

Arm

Intervention/Treatment

Experimental: Arm A (perampanel)

Patients receive perampanel PO daily 40 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Perampanel

Given PO

Other Names:

E2007

Fycompa

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Other: Questionnaire Administration

Ancillary studies

Active Comparator: Arm B (ASD)

Patients receive ASD per standard of care for 40 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Anticonvulsant Agent

Given ASD

Other Names:

Anti-seizure agent

anticonvulsant

Anticonvulsant Agents

Anticonvulsants

antiepileptic

Antiepileptic Agent

Antiepileptics

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Other: Questionnaire Administration

Ancillary studies

Outcome Measures

Primary Outcome Measures

Number of patients with a high-grade glioma who achieve a > 50% reduction in focal seizures with perampanel (PER) 4 mg daily after failing 1 or more anti-seizure drugs (ASDs) [At 3 months]
Will compare seizure frequency before and 3 months after treatment with monotherapy and adjunctive PER and use descriptive statistics to demonstrate differences in responders. A P-value < 0.05 will be used to reflect statistical significance.
Number of patients with a high-grade glioma who achieve a > 50% reduction in focal seizures with PER 4 mg daily after failing 1 or more ASDs [At 6 months]
Will compare seizure frequency before and 6 months after treatment with monotherapy and adjunctive PER and use descriptive statistics to demonstrate differences in responders. A P-value < 0.05 will be used to reflect statistical significance.
Overall survival of patients with high-grade glioma treated with PER [At 3 months]
Chi-square and Student T-test will be used to measure differences in assessment and change during the study period.
Decline in neuropsychological function [At 6 months]
Chi-square and Student T-test will be used to measure differences in assessment and change during the study period.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

The subject, or the subject's legally acceptable representative is willing to participate in a clinical trial, provides written informed consent, and subject provides written assent, as required by the Mayo Clinic Institutional Review Board (IRB) policy involving human subjects. In the event of subject lacking the capacity or losing the ability to consent, consent will be deferred to subject's legally acceptable representative
Subjects that satisfy one of the following diagnostic criteria:
Patients with established clinical diagnoses of biopsy-proven high-grade glioma and epilepsy refractory to at least 1, drug with a seizure frequency of at least 1 seizure episode per month prior to baseline visit
Subjects with body weight of >= 40 kg and =< 125 kg at screening

Exclusion Criteria:

Subject has serious cardiac, respiratory, renal, gastrointestinal, hematologic or other medical condition as determined by the investigator to potentially interfere with the study
Subjects with glioblastoma not following Stupp protocol for treatment of glioblastoma
History of status epilepticus in the 6 months prior to screening or a history of seizure clusters progressing to status epilepticus
Clinically significant suicide risk as determined by the clinician
Positive test result for drugs of abuse at baseline without documented history of stable use for medical purposes or past medical history of drug and/or alcohol abuse
Pregnant or breast-feeding
Subjects treated with PER prior to baseline
Prior felony conviction disclosed by the patient or previously stated in medical record
History of violent behavior
Clinically significant laboratory abnormality at screening or baseline visits, as determined by the investigators
Use of an investigational drug or device within 20 days prior to treatment day 1
Repeated radiation therapy for tumor regrowth
Subjects that plan to undergo tumor resection on or after baseline visit
Uncontrolled psychiatric disorder at baseline
Subjects who report active suicidal attempts or suicidality including subjects with a history of suicide attempts or suicidality determined to be clinically significant by investigators at screening
Biopsy proven high-grade glioma established 3 months prior to enrollment