Perampanel in Seizure Patients With Primary Glial Brain Tumors
Condition: Brain Tumor, Primary
MeSH terms: Brain Neoplasms; Seizures
Intervention: Perampanel
Intervention description: 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
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Perampanel; Seizures

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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

          2. Adult patients (≥ 18 years old)

          3. Karnofsky ≥ 70%

          4. Hematocrit ≥ 29%, ANC ≥ 1,500 cells/L, platelets ≥ 100,000 cells/L

          5. Serum creatinine ≤ 1.5 mg/dL, serum AST and bilirubin ≤ 1.5 times the upper limit of
             normal

          6. 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.

          7. Signed informed consent approved by the Duke Institutional Review Board

        Exclusion Criteria:

          1. Pregnant or breastfeeding (Both perampanel and other Anti-epileptic drugs are
             classified as Pregnancy Category C drugs.)

          2. Chronic excessive use of psycho-pharmaceuticals, alcohol, illicit drugs, or narcotics

          3. Inability to complete or perform measures of patient-reported outcomes or
             neurocognitive testing on the computer

          4. Known allergy to perampanel

          5. Concomitant use of known cytochrome P450 inducers such as carbamazepine, phenytoin, or
             oxcarbazepine (see Appendix A)

          6. Previous history of suicidal ideation, homicidal ideation, depression leading to
             hospitalization or mood disturbance leading to hospitalization.