Perampanel in Seizure Patients With Primary Glial Brain Tumors

NCT02363933 | Completed Phase 4 Results

• 1 other identifier: Pro00055609
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Brain Tumor, Primary

Keywords

Perampanel; Seizures

Outcome Measures

Primary Outcomes (1)

• 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

  20 Weeks

Secondary Outcomes (1)

• Percentage of Patients Who Experience a Adverse Event Possibly, Probably, or Definitely Attributable to Perampanel Treatment

  24 Weeks

Study Arms (1)

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.

Drug: Perampanel

Interventions

Perampanel DRUG

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

Also known as: FYCOMPA

Perampanel + Current Anti-Epileptic Drug

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

The Preston Robert Tisch Brain Tumor Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Seizures

Interventions

perampanel

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Katherine Peters, MD, PhD
• Organization: Duke University Medical Center

katherine.peters@duke.edu

9196846173

Study Officials

• Katherine B Peters, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2015
• First Posted: February 16, 2015
• Study Start: April 7, 2015
• Primary Completion: March 14, 2017
• Study Completion: April 10, 2017
• Last Updated: April 27, 2018
• Results First Posted: April 2, 2018

Record last verified: 2018-03

Locations

US (1)