Intractable Epilepsy, Malignant Glioma, Seizure Disorder, WHO Grade 2 Glioma, WHO Grade 3 Glioma
Conditions
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.
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.
Interventions
DRUGAnticonvulsant Agent
Given ASD
DRUGPerampanel
Given PO
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Number of Participants Alive at 3 Months 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A (Perampanel) Patients receive perampanel PO QD for 40 weeks in the absence of disease progression or unacceptable toxicity.
Perampanel: Given PO
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies | 3 |
| Arm B (ASD) Patients receive ASD per standard of care for 40 weeks in the absence of disease progression or unacceptable toxicity.
Anticonvulsant Agent: Given ASD
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies | 1 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study was Terminated | 2 | 1 |
Baseline characteristics
| Characteristic | Arm A (Perampanel) | Arm B (ASD) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment United States | 3 participants | 1 participants | 4 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 2 / 3 | 0 / 1 |
| serious Total, serious adverse events | 0 / 3 | 0 / 1 |
Outcome results
Primary
Decline in Neuropsychological Function
Chi-square and Student T-test will be used to measure differences in assessment and change during the study period.
Time frame: At 6 months
Population: The study was terminated due to the funding sponsor no longer being able to provide study medication. Data for this outcome measure was not collected nor analyzed.
Primary
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.
Time frame: At 3 months
Population: 1 participant was randomized to Arm B, but did not receive PER treatment. In Arm A, only 2 participants met the study 3 month mark prior to study termination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A (Perampanel) | Number of Participants Alive at 3 Months With High-grade Glioma Treated With PER | 2 Participants |
Primary
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.
Time frame: At 6 months
Population: 1 participant was randomized to Arm B, but did not complete the 6 month follow-up due to study termination. In Arm A, only 1 participant met the study 6 month mark prior to study termination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A (Perampanel) | 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 | 1 Participants |
Primary
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.
Time frame: At 3 months
Population: 1 participant was randomized to Arm B, but did not complete the 3 month follow-up due to study termination. In Arm A, only 2 participants met the study 3 month mark prior to study termination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A (Perampanel) | 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) | 1 Participants |