Glioma, MalignantPhase 1/2NCT04497142
Effect of Perampanel on Peritumoral Hyperexcitability in HGG
A Phase 1/2 study testing Perampanel in people with Glioma, Malignant and Surgery, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma, Malignant, Surgery, Seizures
- What is being tested?
- Perampanel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Nov 2020to 16 May 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- The effects of perampanel on the developing human fetus are unknown. For this reason and because some anti-seizure medications are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02215
About this study
Official title: Pilot Study of Perampanel on Peritumoral Hyperexcitability and Seizure Control in Newly Diagnosed High Grade Glioma
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)
Read the detailed description
This research study is a Pilot Study, which is the first time investigators are examining brain activity after taking perampanel.
The U.S. Food and Drug Administration (FDA) has approved perampanel as a treatment option for seizures. It has not been approved for the treatment of brain tumors. Recording of brain activity (electrocorticography) during surgery is an established clinical procedure, which will be performed for investigational purposes. This research study is studying brain recordings and perampanel treatment in participants with brain tumors for the following reasons:
- People with brain tumors commonly have seizures.
- Perampanel was developed as an anti-seizure medication, which works by blocking a signaling pathway between brain cells, mediated by AMPA receptors.
- Previous research has shown abnormal brain activity around tumors resulting from increased AMPA receptor activation.
- Perampanel is expected to decrease abnormal brain activity and prevent seizures by blocking AMPA receptor signaling.
This study involves two groups of participants, one group who receives the antiseizure medication perampanel, and the other group who receives the usual antiseizure medication (typically levetiracetam) at the time of surgery. Participants have the option to choose which group to participate if they have a preference.
The research study procedures include screening for eligibility, recording brain activity during surgery, and study treatment including evaluations and follow up visits. Participants will receive the study drug 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.
It is expected that about 20 people will take part in this research study.
The National Institute of Health (NIH) is supporting this study by providing funding for the research. Eisai Inc, a pharmaceutical company, is supporting this research study by providing the study medication.
- Conditions
- Glioma, Malignant, Surgery, Seizures
- Being tested
- Perampanel, Standard of Care
- Keywords
- Glioma, Surgery, Seizures
- Medical subject headings
- Glioma, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PerampanelDrug
Also called E2007, Fycompa
Tablet taken orally 1x daily.
Standard of CareDrug
Also called Standard treatment (typically the anti-seizure medication levetiracetam)
Predetermined standard of care drug and dosing
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Peri-operative
Secondary outcomes (1)
Seizure-freedom
Seizure-free rates were assessed from the time of initial glioma resection to radiographic tumor progression or up to a maximum of 12 months.
Measured: From time of initial surgery to PD or up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2020
- Study start5 Nov 2020
- Primary completion16 May 2023
- Study completion16 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioma, MalignantStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Eisai Inc.
- Responsible party
- Principal investigator, Jong Woo Lee, MD PhD, Dana-Farber Cancer Institute
- Investigators
- Jong Woo Lee, MD, PhD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04497142
- Sponsor's protocol ID
- 20-059
- Other IDs
- 2P50CA165962-06A1
- Status last verified
- Jul 2024
- First submitted
- 30 Jul 2020
- Last updated
- 5 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Steven Tobochnik, MD at stobochnik@bwh.harvard.edu. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Publications
Tobochnik S, Regan MS, Dorotan MKC, Reich D, Lapinskas E, Hossain MA, Stopka S, Meredith DM, Santagata S, Murphy MM, Arnaout O, Bi WL, Chiocca EA, Golby AJ, Mooney MA, Smith TR, Ligon KL, Wen PY, Agar NYR, Lee JW. Pilot Trial of Perampanel on Peritumoral Hyperexcitability in Newly Diagnosed High-grade Glioma. Clin Cancer Res. 2024 Dec 2;30(23):5365-5373. doi: 10.1158/1078-0432.CCR-24-1849.
PubMed 39499201
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Perampanel on Peritumoral Hyperexcitability and Seizure Control in Newly Diagnosed High Grade Glioma
- ClinicalTrials.gov ID
- NCT04497142
- Acronym / sponsor ID
- 20-059
- Conditions
- Glioma, Malignant, Surgery, Seizures
- Keywords
- Glioma, Surgery, Seizures
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Eisai Inc.
- Study start
- 5 Nov 2020 (actual)
- Primary completion
- 16 May 2023 (actual)
- Study completion
- 16 May 2023 (actual)
- First posted
- 4 Aug 2020 (actual)
- Results
- Posted 5 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Detailed description
This research study is a Pilot Study, which is the first time investigators are examining brain activity after taking perampanel.
The U.S. Food and Drug Administration (FDA) has approved perampanel as a treatment option for seizures. It has not been approved for the treatment of brain tumors. Recording of brain activity (electrocorticography) during surgery is an established clinical procedure, which will be performed for investigational purposes. This research study is studying brain recordings and perampanel treatment in participants with brain tumors for the following reasons:
- People with brain tumors commonly have seizures.
- Perampanel was developed as an anti-seizure medication, which works by blocking a signaling pathway between brain cells, mediated by AMPA receptors.
- Previous research has shown abnormal brain activity around tumors resulting from increased AMPA receptor activation.
- Perampanel is expected to decrease abnormal brain activity and prevent seizures by blocking AMPA receptor signaling.
This study involves two groups of participants, one group who receives the antiseizure medication perampanel, and the other group who receives the usual antiseizure medication (typically levetiracetam) at the time of surgery. Participants have the option to choose which group to participate if they have a preference.
The research study procedures include screening for eligibility, recording brain activity during surgery, and study treatment including evaluations and follow up visits. Participants will receive the study drug 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.
It is expected that about 20 people will take part in this research study.
The National Institute of Health (NIH) is supporting this study by providing funding for the research. Eisai Inc, a pharmaceutical company, is supporting this research study by providing the study medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Perampanel | Experimental | Drug: Perampanel* 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. |
| Standard of Care | Active comparator | Drug: Standard of Care* 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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:
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PerampanelAlso: E2007, FycompaTablet taken orally 1x daily. | Drug | Perampanel |
| Standard of CareAlso: Standard treatment (typically the anti-seizure medication levetiracetam)Predetermined standard of care drug and dosing | Drug | Standard of Care |
Primary outcome
Peritumoral HFO Rate
Time frame: Peri-operative
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.
1 secondary outcome
Seizure-freedom
Time frame: From time of initial surgery to PD or up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39499201Tobochnik S, Regan MS, Dorotan MKC, Reich D, Lapinskas E, Hossain MA, Stopka S, Meredith DM, Santagata S, Murphy MM, Arnaout O, Bi WL, Chiocca EA, Golby AJ, Mooney MA, Smith TR, Ligon KL, Wen PY, Agar NYR, Lee JW. Pilot Trial of Perampanel on Peritumoral Hyperexcitability in Newly Diagnosed High-grade Glioma. Clin Cancer Res. 2024 Dec 2;30(23):5365-5373. doi: 10.1158/1078-0432.CCR-24-1849.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Steven Tobochnik, MD at stobochnik@bwh.harvard.edu. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jong Woo Lee, MD, PhD principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Perampanel in people with Glioma, Malignant and Surgery, run by Dana-Farber Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peritumoral HFO Rate (time frame: Peri-operative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04497142, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2024.