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

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

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.

Study Overview

• Status: Terminated
• Conditions: Malignant Glioma; WHO Grade 3 Glioma; Intractable Epilepsy; Seizure Disorder; WHO Grade 2 Glioma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Perampanel; Drug: Anticonvulsant Agent

Detailed Description

PRIMARY OBJECTIVE:

I. 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:

I. 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.

II. 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) for 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 Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida

Participation Criteria

Eligibility Criteria

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

Description

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 meet the following diagnostic criteria:

  • Patients with established clinical diagnoses of biopsy-proven high-grade glioma (grade II or above) 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
• Adults age 18 and older

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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	At 3 months
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	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.	At 6 months
Number of Participants Alive at 3 Months With High-grade Glioma Treated With PER	Chi-square and Student T-test will be used to measure differences in assessment and change during the study period.	At 3 months
Decline in Neuropsychological Function	Chi-square and Student T-test will be used to measure differences in assessment and change during the study period.	At 6 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: William Tatum, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2020
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: November 11, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (Actual): December 2, 2020

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: May 27, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; 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; Epilepsy; Glioma; Seizures; Epilepsies, Partial; Drug Resistant Epilepsy; Anticonvulsants
• Other Study ID Numbers: 19-006286 (Mayo Clinic in Florida); NCI-2020-01290 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); MC2072 (Other Identifier: Mayo Clinic)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No