Glioma, Malignant, Seizures, Surgery
Conditions
Keywords
Glioma, Surgery, Seizures
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)
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.
Interventions
DRUGPerampanel
Tablet taken orally 1x daily.
DRUGStandard of Care
Predetermined standard of care drug and dosing
Sponsors
National Cancer Institute (NCI)
Eisai Inc.
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peritumoral HFO Rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seizure-freedom | From time of initial surgery to PD or up to 12 months | Seizure-free rates were assessed from the time of initial glioma resection to radiographic tumor progression or up to a maximum of 12 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Perampanel + Electrocorticography Perampanel 6mg on day prior to resection, 4mg pre-op prior to resection, and 4mg daily until PD or up to 12 months. Intraoperative ECoG with 20 contact subdural grid performed for analysis of high frequency oscillation (80-500 Hz) rate. | 8 |
| Standard of Care + Electrocorticography Levetiracetam peri-operatively per standard of care. Intraoperative ECoG with 20 contact subdural grid performed for analysis of high frequency oscillation (80-500 Hz) rate. | 4 |
| Total | 12 |
Baseline characteristics
| Characteristic | Perampanel + Electrocorticography | Standard of Care + Electrocorticography | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 1 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 4 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 7 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 4 |
| other Total, other adverse events | 7 / 8 | 4 / 4 |
| serious Total, serious adverse events | 0 / 8 | 0 / 4 |
Outcome results
Primary
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.
Time frame: Peri-operative
Population: 1 participant (perampanel arm) was excluded from analysis after pathology revealed a non-glial tumor
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Perampanel + Electrocorticography | Peritumoral HFO Rate | 2.5 HFOs per minute |
| Standard of Care + Electrocorticography | Peritumoral HFO Rate | 1.4 HFOs per minute |
Secondary
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.
Time frame: From time of initial surgery to PD or up to 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Perampanel + Electrocorticography | Seizure-freedom | 1 Participants |
| Standard of Care + Electrocorticography | Seizure-freedom | 2 Participants |