None listed
Conditions
Brief summary
The aim of this study is to examine effectiveness of perampanel in the prevention of tumour associated epilepsy (TAE) in patients with grade II-III gliomas. Who is it for? You may be eligible to join this study if you are aged 18-65 years and have a diagnosis of World Health Organisation grade II-III supratentorial glioma and have not experienced a pre-operative seizure. Study details Patients will be randomized (allocated by chance) to receive perampanel, or or placebo for 16 week. Doses will be escalated over the first four week before patients enter an assessment phase for the remainder of the trial. Patients will be followed up for 52 weeks. The primary outcomes are i) time to first seizure after escalation phase (weeks 5-52) and ii) proportion of patients seizure free during 12 week assessment phase. Secondary endpoints include measures of drug safety, tolerability and quality of life. Glutamate concentrations will be measured before drug treatment is commenced to assess whether it can be utilized to predict both post-operative seizure and response to perampanel. This will be the first monotherapy epilepsy RCT utilizing perampanel. A positive study would support a larger randomized phase III trial examining perampanel monotherapy in tumour associated seizures prophylaxis. The novel use of 7T MRI to quantify glutamate offers the opportunity to assess if a non-invasive biomarker can help stratify seizure risk and perampanel response. This can pave the way for individualised and targeted epilepsy treatment and prevention.
Interventions
The interventional drug to be utilized in this randomized controlled trial is the oral anti-epileptic drug, perampanel. Perampanel is an AMPA-receptor antagonist. Both intervention and comparator (placebo) medications will be identically encapsulated.
Patients with WHO grade II-III supratentorial gliomas will be recruited pre-operatively and receive a 7T MRI scan. Post-operatively, patients will be randomized to receive perampanel or placebo for 16 weeks and be observed for a further 36 weeks,
The interventional drug to be utilized in this randomized controlled trial is the oral anti-epileptic drug, perampanel. Perampanel is an AMPA-receptor antagonist. Both intervention and comparator (placebo) medications will be identically encapsulated. Patients with WHO grade II-III supratentorial gliomas will be recruited pre-operatively and receive a 7T MRI scan. Post-operatively, patients will be randomized to receive perampanel or placebo for 16 weeks and be observed for a further 36 weeks, until at the study ends at 52 weeks. For patients randomized to the active arm, perampanel will be started at 2mg at night and over the first 4 weeks (escalation phase) will be uptitrated to by 2mg every 2 weeks, eg 2mg for the first 2 weeks, then 4mg for following two weeks. At the start of the assessment phase assessment phase (week 5-16), perampanel will be increased to 6mg. Participants will remain on 6mg from week 5 until the end of week 16 unless seizures or side effects occur. At the end of the assessment phase all medications will be ceased and patients will enter the observation phase (week 17-52). Participants will have 8 visits after randomization over the 52-week study period, during which post-operative seizures, compliance and side effects will be assessment by investigators. In escalation and assessment phases, participants will be questioned regarding their medication adherence, and tablet/bottle counting will be performed to aid in compliance assessment. Visits will occur at 2, 4, 6, 8 weeks and 4, 6, 9, 12 months. If post-operative seizures occur during the escalation phase, then after assessment by a study neurologist, standard titration will continue to occur if clinically appropriate. If seizures occur during the assessment or observation phase, or multiple seizures occur during escalation phase, then the endpoint will be reached and blind broken. The patient will be withdrawn from the study at this point and managed as per their treating physician. If side effects develop and are intolerable, one dose reduction of 2mg can occur.
Sponsors
Melbourne Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Pre-operative phase (ie inclusion for 7T MRI) 1. 18 – 80 years 2. Radiological diagnosis of a supratentorial WHO grade II-III glioma 3. Planned surgical resection or biopsy of lesion 4. 3T MRI performed as clinical standard of care 5. Able to give informed consent 6. No pre-operative seizure Post-operative phase (ie inclusion for treatment intervention) 1. 18-80 years 2. Diagnosis of WHO grade II-III glioma 3. Less than 3 weeks from date of glioma resection or biopsy 4. No seizures prior to randomisation
Exclusion criteria
1. Previous non-tumour related neurosurgical procedures (excluding biopsy of glioma) 2. Pre-operative chemotherapy or radiotherapy 3. Receiving >1000mg daily of levetiracetam or multiple concurrent anti-epileptic drugs at time of randomization 4. Contraindication to 7T MRI 5. Significant risk factors for non-tumour associated epilepsy - Previously diagnosed epilepsy (excluding benign childhood epilepsies) - Additional epileptogenic intra-cranial pathology (including intra-cranial complications from glioma resection) 6. History of major psychiatric morbidity (such as psychiatric illness requiring hospitalisation or history of psychosis, major depression or suicidality) within the last 2 years 7. Pregnant or breast-feeding 8. Excessive alcohol or recreational drug use
Outcome results
None listed