Effect of Perampanel on Peritumoral Hyperexcitability in HGG

NCT04497142 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 20-0592P50CA165962-06A1
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to learn more about seizures in people with primary brain tumors. It will evaluate whether an antiseizure medication decreases hyperexcitability activity around tumors and prevents seizures. The procedure and study drug involved in this study are:

• Electrocorticography
• Perampanel (Fycompa)

Conditions

Glioma, Malignant; Surgery; Seizures

Keywords

Glioma; Surgery; Seizures

Outcome Measures

Primary Outcomes (1)

• Peritumoral HFO Rate

  Peritumoral hyperexcitability was measured by intraoperative electrocorticography (ECoG) high frequency oscillation (80-500 Hz) rate over 10 minutes within 1 cm of the contrast-enhancing margin at the time of initial glioma resection.

  Peri-operative

Secondary Outcomes (1)

• Seizure-freedom

  From time of initial surgery to PD or up to 12 months

Study Arms (2)

Perampanel

EXPERIMENTAL

* Participants will take a predetermined first dose of perampanel on the day before their tumor surgery * During surgery, an approximately 4x6cm recording grid will be placed on the surface of the brain over the tumor, and brain activity around the tumor will be recorded for 10 minutes during surgery (Electrocorticography). * After surgery participants will take perampanel at a predetermined dose once a day for as long as they do not have serious side effects and their disease does not get worse, up to a maximum of 12 months. Participants will be provided a drug and seizure diary to document drug and seizure information and have monthly study visits either in clinic or by phone.

Drug: Perampanel

Standard of Care

ACTIVE COMPARATOR

* Participants will receive standard of care medication before surgery. * During surgery, an approximately 4x6cm recording grid will be placed on the surface of the brain over the tumor, and brain activity around the tumor will be recorded for 10 minutes during surgery (Electrocorticography). * After surgery participants will take standard of care medications as predetermined by their doctor. Participants will be provided a drug and seizure diary to document drug and seizure information and have monthly study visits either in clinic or by phone. * Participants will be followed up to 12 months after completing surgery.

Drug: Standard of Care

Interventions

Perampanel DRUG

Tablet taken orally 1x daily.

Also known as: E2007, Fycompa

Perampanel

Standard of Care DRUG

Predetermined standard of care drug and dosing

Also known as: Standard treatment (typically the anti-seizure medication levetiracetam)

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have radiologic evidence of anaplastic astrocytoma or glioblastoma multiforme within 14 days of enrollment.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm (≥1 cm) with CT or MRI. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.
• Age ≥18 years.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• Participants must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤ institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
• glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 (see Appendix B)
• Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.

You may not qualify if:

• Participants with brain metastases due to confounding effects on the study objectives.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to perampanel.
• Participants receiving any medications or substances that are moderate or strong inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• Participants with uncontrolled intercurrent illness.
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because perampanel is an anti-seizure agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with perampanel, breastfeeding should be discontinued if the mother is treated with perampanel.
• Participants with a history of suicide attempt or current active suicidal ideation with intent as defined by Columbia Suicide Severity Rating Scale (C-SSRS) type 4-5, due to the potential for suicidal ideation with the use of all anti-seizure medications.
• Participants who are unable to swallow pills.
• Participants with tumor associated seizures greater than one month before planned surgery.
• Participants currently receiving treatment with more than one anti-seizure medication.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• Eisai Inc.: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Glioma; Seizures

Interventions

perampanel; Standard of Care

Condition Hierarchy (Ancestors)

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; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

Early termination after planned interim analysis for futility. 1 participant (perampanel arm) was excluded from outcome analysis after pathology revealed a non-glial tumor, but was included in safety assessment.

Results Point of Contact

• Title: Steven Tobochnik, MD
• Organization: Brigham and Women's Hospital

stobochnik@bwh.harvard.edu

617-732-7432

Study Officials

• Jong Woo Lee, MD, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 30, 2020
• First Posted: August 4, 2020
• Study Start: November 5, 2020
• Primary Completion: May 16, 2023
• Study Completion: May 16, 2023
• Last Updated: August 5, 2024
• Results First Posted: August 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)