Brain Tumor, PrimaryPhase 4NCT02363933
Perampanel in Seizure Patients With Primary Glial Brain Tumors
A Phase 4 study testing Perampanel in people with Brain Tumor, Primary, run by Duke University at 1 site in United States.
Trial summary
This is a Phase 2 single-arm study to assess the efficacy of perampanel as an adjunctive anti-epileptic drug (AED) in patients with primary glioma that are presenting refractory partial onset seizure activity (defined as 3 or more seizures in a 28-day period). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Tumor, Primary
- What is being tested?
- Perampanel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Apr 2015to 10 Apr 2017
- Phase
- Phase 4
- 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
- Patients must be diagnosed with a primary glioma and have refractory partial onset seizure activity (defined as 3 or more seizures in a 28-day period) on levetiracetam monotherapy
- Adult patients (≥ 18 years old)
- Karnofsky ≥ 70%
- Hematocrit ≥ 29%, ANC ≥ 1,500 cells/L, platelets ≥ 100,000 cells/L
- Serum creatinine ≤ 1.5 mg/dL, serum AST and bilirubin ≤ 1.5 times the upper limit of normal
- If sexually active, patients will take contraceptive measures for the duration of protocol treatment and continue until two months after treatment. The effectiveness of hormonal contraceptives containing levonorgestrel has been shown to be reduced by perampanel at a 12 mg dose.1 Therefore, alternative or back-up methods of contraception are recommended.
- Signed informed consent approved by the Duke Institutional Review Board
Who cannot join
- Pregnant or breastfeeding (Both perampanel and other Anti-epileptic drugs are classified as Pregnancy Category C drugs.)
- Chronic excessive use of psycho-pharmaceuticals, alcohol, illicit drugs, or narcotics
- Inability to complete or perform measures of patient-reported outcomes or neurocognitive testing on the computer
- Known allergy to perampanel
- Concomitant use of known cytochrome P450 inducers such as carbamazepine, phenytoin, or oxcarbazepine (see Appendix A)
- Previous history of suicidal ideation, homicidal ideation, depression leading to hospitalization or mood disturbance leading to hospitalization.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Preston Robert Tisch Brain Tumor Center
Durham, North Carolina, 27710
About this study
Official title: Phase II Feasibility Study to Evaluate the Efficacy and Safety of Perampanel in Seizure Patients With Primary Glial Brain Tumors
This is a Phase 2 single-arm study to assess the efficacy of perampanel as an adjunctive anti-epileptic drug (AED) in patients with primary glioma that are presenting refractory partial onset seizure activity (defined as 3 or more seizures in a 28-day period). In this study, patients will be started on a dose of 2 mg of perampanel daily taken orally at bedtime for 2 weeks. At the start of week 3 perampanel will be titrated up in dose in 2mg increments per week up to 8mg daily, as long as it is well tolerated by the patient. The highest dose of perampanel will be 8 mg orally at bedtime. Once this is achieved, patients will remain on a maintenance dose of 8 mg for 12 more weeks. The planned treatment dose is 8mg, but the dose can be modified by the physician based on patient reported tolerability. Titration and taper periods will be determined by the physician in the case where patients do not reach the planned treatment dose of 8 mg daily. Patients will be assessed in the Brain Tumor Center Clinic every 8 weeks. Study assessments will be made at enrollment, 8 weeks, 16 weeks, and 24 weeks. Assessments will include history and physical examination (H\&P) including Karnofsky Performance Status (KPS), neurological examination, evaluation of seizure history, patient-reported outcomes of QoL, and computer based neurocognitive testing. After a total of 16 weeks of therapy, perampanel will be tapered down. At Week 17, patients will begin taking 6mg of perampanel, Week 18 4mg, Week 19 2mg, and Week 20 they will no longer take perampanel. Patients will be considered off treatment at the end of week 20, once perampanel has cleared their system. Patients will then be monitored through Week 24. Patients will continue to take their original AED regimen after they stop perampanel. If seizure control is achieved during the maintenance period or if seizures occur during the tapering period, patients can be continued on perampanel per the discretion of the treating physician. In this instance, perampanel will be prescribed by the treating physician and not provided within the confines of the study. Efficacy will be assessed using a log of patient-reported seizure activity. As is standard procedure at the Preston Robert Tisch Brain Tumor Center (PRTBTC), patients will be given a log to record the number of seizures that occur. Research team members will regularly contact patients for reminders and reports from the log. Safety will be assessed with the following laboratory evaluations: complete blood count (CBC) with differential, complete metabolic panel (CMP), and toxicity assessment.
Read the detailed description
This is a Phase 2 single-arm study to assess the efficacy of perampanel as an adjunctive anti-epileptic drug (AED) in patients with primary glioma that are presenting refractory partial onset seizure activity (defined as 3 or more seizures in a 28-day period). In this study, patients will be started on a dose of 2 mg of perampanel daily taken orally at bedtime for 2 weeks. At the start of week 3 perampanel will be titrated up in dose in 2mg increments per week up to 8mg daily, as long as it is well tolerated by the patient. The highest dose of perampanel will be 8 mg orally at bedtime. Once this is achieved, patients will remain on a maintenance dose of 8 mg for 12 more weeks. The planned treatment dose is 8mg, but the dose can be modified by the physician based on patient reported tolerability. Titration and taper periods will be determined by the physician in the case where patients do not reach the planned treatment dose of 8 mg daily. Patients will be assessed in the Brain Tumor Center Clinic every 8 weeks. Study assessments will be made at enrollment, 8 weeks, 16 weeks, and 24 weeks. Assessments will include history and physical examination (H\&P) including Karnofsky Performance Status (KPS), neurological examination, evaluation of seizure history, patient-reported outcomes of QoL, and computer based neurocognitive testing. After a total of 16 weeks of therapy, perampanel will be tapered for 3 weeks and then will be discontinued, such that Week 20 patients will no longer be taking perampanel. Patients will then be monitored through Week 24. Patients will continue to take their original AED regimen after they stop perampanel. Patients will remain on their original AED regimen during this treatment time and the dose of their original AED regimen at the start of the study will not be changed while they are on study. If seizure control is achieved during the maintenance period or if seizures occur during the tapering period, patients can be continued on perampanel per the discretion of the treating physician. In this instance, perampanel will be prescribed by the treating physician and not provided within the confines of the study. Efficacy will be assessed using a log of patient-reported seizure activity. As is standard procedure at the PRTBTC, patients will be given a log to record the number of seizures that occur. Research team members will regularly contact patients for reminders and reports from the log. Safety will be assessed with the following laboratory evaluations: complete blood count (CBC) with differential, complete metabolic panel (CMP), and toxicity assessment.
This study has been designed with 90% power to detect an increase in the 50% responder rate during the maintenance period from a benchmark of 20% to 35%. Assuming a type I error rate of 0.1, 61 patients will be required. Based on prior studies the early discontinuation rate was 16%, therefore 71 patients will be enrolled to compensate for patients discontinuing prior to the completion of the maintenance period.
- Conditions
- Brain Tumor, Primary
- Being tested
- Perampanel
- Keywords
- Perampanel, Seizures
- Medical subject headings
- Brain Neoplasms, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PerampanelDrug
Also called FYCOMPA
Perampanel is a highly selective non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptor antagonist that has shown efficacy in a randomized phase III study for refractory partial-onset seizures
| Study group | Role | What they receive |
|---|---|---|
| Perampanel + Current Anti-Epileptic Drug | Experimental | Primary glioma patients will receive perampanel along with their current AED for a total of 20 weeks. Perampanel will be titrated from 2 mg in weeks 1 and 2 and up to 8 mg daily by week 5 if well tolerated by the patient. They will then receive a maintenance dose of 8 mg per day through 16 weeks. After 16 weeks, subjects will be tapered off perampanel over a 4 week period. Receives: Drug: Perampanel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients With ≥50% Seizure Reduction During the Maintenance Period Compared With Seizure Frequency Before Initiation of Perampanel
The primary objective of this study is to assess the efficacy of perampanel as an adjunctive anti-epileptic drug (AED) in patients with primary glioma presenting refractory partial onset seizure activity. Efficacy will be assessed by the 50% responder rate, defined as the percentage of patients with a ≥50% seizure reduction during the maintenance period compared with the seizure frequency before initiation of perampanel. Seizure frequency during maintenance perampanel will be computed as the ratio of the total number of seizure episodes while receiving perampanel during the maintenance period and the number of days perampanel is administered
Measured: 20 Weeks
Secondary outcomes (1)
Percentage of Patients Who Experience a Adverse Event Possibly, Probably, or Definitely Attributable to Perampanel Treatment
The percentage of patients with unacceptable adverse events that are possibly, probably, or definitely related to perampanel treatment will be calculated. Unacceptable adverse events include all Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 Grade 4 or 5 toxicities that are possibly, probably, or definitely related to perampanel, as well as suicidal ideation (any grade) or suicide attempt (Grade 3-5).
Measured: 24 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2015 (estimated)
- Study start7 Apr 2015
- Primary completion14 Mar 2017
- Study completion10 Apr 2017
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.
- Other trials for Brain Tumor, PrimaryStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Katherine B Peters, MD, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02363933
- Sponsor's protocol ID
- Pro00055609
- Status last verified
- Mar 2018
- First submitted
- 10 Feb 2015
- Last updated
- 27 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Feasibility Study to Evaluate the Efficacy and Safety of Perampanel in Seizure Patients With Primary Glial Brain Tumors
- ClinicalTrials.gov ID
- NCT02363933
- Acronym / sponsor ID
- Pro00055609
- Conditions
- Brain Tumor, Primary
- Keywords
- Perampanel, Seizures
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 7 Apr 2015 (actual)
- Primary completion
- 14 Mar 2017 (actual)
- Study completion
- 10 Apr 2017 (actual)
- First posted
- 16 Feb 2015 (estimated)
- Results
- Posted 2 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2 single-arm study to assess the efficacy of perampanel as an adjunctive anti-epileptic drug (AED) in patients with primary glioma that are presenting refractory partial onset seizure activity (defined as 3 or more seizures in a 28-day period). In this study, patients will be started on a dose of 2 mg of perampanel daily taken orally at bedtime for 2 weeks. At the start of week 3 perampanel will be titrated up in dose in 2mg increments per week up to 8mg daily, as long as it is well tolerated by the patient. The highest dose of perampanel will be 8 mg orally at bedtime. Once this is achieved, patients will remain on a maintenance dose of 8 mg for 12 more weeks. The planned treatment dose is 8mg, but the dose can be modified by the physician based on patient reported tolerability. Titration and taper periods will be determined by the physician in the case where patients do not reach the planned treatment dose of 8 mg daily. Patients will be assessed in the Brain Tumor Center Clinic every 8 weeks. Study assessments will be made at enrollment, 8 weeks, 16 weeks, and 24 weeks. Assessments will include history and physical examination (H\&P) including Karnofsky Performance Status (KPS), neurological examination, evaluation of seizure history, patient-reported outcomes of QoL, and computer based neurocognitive testing. After a total of 16 weeks of therapy, perampanel will be tapered down. At Week 17, patients will begin taking 6mg of perampanel, Week 18 4mg, Week 19 2mg, and Week 20 they will no longer take perampanel. Patients will be considered off treatment at the end of week 20, once perampanel has cleared their system. Patients will then be monitored through Week 24. Patients will continue to take their original AED regimen after they stop perampanel. If seizure control is achieved during the maintenance period or if seizures occur during the tapering period, patients can be continued on perampanel per the discretion of the treating physician. In this instance, perampanel will be prescribed by the treating physician and not provided within the confines of the study. Efficacy will be assessed using a log of patient-reported seizure activity. As is standard procedure at the Preston Robert Tisch Brain Tumor Center (PRTBTC), patients will be given a log to record the number of seizures that occur. Research team members will regularly contact patients for reminders and reports from the log. Safety will be assessed with the following laboratory evaluations: complete blood count (CBC) with differential, complete metabolic panel (CMP), and toxicity assessment.
Detailed description
This is a Phase 2 single-arm study to assess the efficacy of perampanel as an adjunctive anti-epileptic drug (AED) in patients with primary glioma that are presenting refractory partial onset seizure activity (defined as 3 or more seizures in a 28-day period). In this study, patients will be started on a dose of 2 mg of perampanel daily taken orally at bedtime for 2 weeks. At the start of week 3 perampanel will be titrated up in dose in 2mg increments per week up to 8mg daily, as long as it is well tolerated by the patient. The highest dose of perampanel will be 8 mg orally at bedtime. Once this is achieved, patients will remain on a maintenance dose of 8 mg for 12 more weeks. The planned treatment dose is 8mg, but the dose can be modified by the physician based on patient reported tolerability. Titration and taper periods will be determined by the physician in the case where patients do not reach the planned treatment dose of 8 mg daily. Patients will be assessed in the Brain Tumor Center Clinic every 8 weeks. Study assessments will be made at enrollment, 8 weeks, 16 weeks, and 24 weeks. Assessments will include history and physical examination (H\&P) including Karnofsky Performance Status (KPS), neurological examination, evaluation of seizure history, patient-reported outcomes of QoL, and computer based neurocognitive testing. After a total of 16 weeks of therapy, perampanel will be tapered for 3 weeks and then will be discontinued, such that Week 20 patients will no longer be taking perampanel. Patients will then be monitored through Week 24. Patients will continue to take their original AED regimen after they stop perampanel. Patients will remain on their original AED regimen during this treatment time and the dose of their original AED regimen at the start of the study will not be changed while they are on study. If seizure control is achieved during the maintenance period or if seizures occur during the tapering period, patients can be continued on perampanel per the discretion of the treating physician. In this instance, perampanel will be prescribed by the treating physician and not provided within the confines of the study. Efficacy will be assessed using a log of patient-reported seizure activity. As is standard procedure at the PRTBTC, patients will be given a log to record the number of seizures that occur. Research team members will regularly contact patients for reminders and reports from the log. Safety will be assessed with the following laboratory evaluations: complete blood count (CBC) with differential, complete metabolic panel (CMP), and toxicity assessment.
This study has been designed with 90% power to detect an increase in the 50% responder rate during the maintenance period from a benchmark of 20% to 35%. Assuming a type I error rate of 0.1, 61 patients will be required. Based on prior studies the early discontinuation rate was 16%, therefore 71 patients will be enrolled to compensate for patients discontinuing prior to the completion of the maintenance period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Perampanel + Current Anti-Epileptic Drug | Experimental | Drug: PerampanelPrimary glioma patients will receive perampanel along with their current AED for a total of 20 weeks. Perampanel will be titrated from 2 mg in weeks 1 and 2 and up to 8 mg daily by week 5 if well tolerated by the patient. They will then receive a maintenance dose of 8 mg per day through 16 weeks. After 16 weeks, subjects will be tapered off perampanel over a 4 week period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must be diagnosed with a primary glioma and have refractory partial onset seizure activity (defined as 3 or more seizures in a 28-day period) on levetiracetam monotherapy
- Adult patients (≥ 18 years old)
- Karnofsky ≥ 70%
- Hematocrit ≥ 29%, ANC ≥ 1,500 cells/L, platelets ≥ 100,000 cells/L
- Serum creatinine ≤ 1.5 mg/dL, serum AST and bilirubin ≤ 1.5 times the upper limit of normal
Key exclusion criteria (6 listed)
- Pregnant or breastfeeding (Both perampanel and other Anti-epileptic drugs are classified as Pregnancy Category C drugs.)
- Chronic excessive use of psycho-pharmaceuticals, alcohol, illicit drugs, or narcotics
- Inability to complete or perform measures of patient-reported outcomes or neurocognitive testing on the computer
- Known allergy to perampanel
- Concomitant use of known cytochrome P450 inducers such as carbamazepine, phenytoin, or oxcarbazepine (see Appendix A)
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: FYCOMPAPerampanel is a highly selective non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptor antagonist that has shown efficacy in a randomized phase III study for refractory partial-onset seizures | Drug | Perampanel + Current Anti-Epileptic Drug |
Primary outcome
Percentage of Patients With ≥50% Seizure Reduction During the Maintenance Period Compared With Seizure Frequency Before Initiation of Perampanel
Time frame: 20 Weeks
The primary objective of this study is to assess the efficacy of perampanel as an adjunctive anti-epileptic drug (AED) in patients with primary glioma presenting refractory partial onset seizure activity. Efficacy will be assessed by the 50% responder rate, defined as the percentage of patients with a ≥50% seizure reduction during the maintenance period compared with the seizure frequency before initiation of perampanel. Seizure frequency during maintenance perampanel will be computed as the ratio of the total number of seizure episodes while receiving perampanel during the maintenance period and the number of days perampanel is administered
1 secondary outcome
Percentage of Patients Who Experience a Adverse Event Possibly, Probably, or Definitely Attributable to Perampanel Treatment
Time frame: 24 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Katherine B Peters, MD, PhD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Perampanel in people with Brain Tumor, Primary, run by Duke University 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 7 inclusion and 6 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 27 Apr 2018. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 2 Apr 2018). 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?
Percentage of Patients With ≥50% Seizure Reduction During the Maintenance Period Compared With Seizure Frequency Before Initiation of Perampanel (time frame: 20 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Apr 2018.