Efficacy and Safety of Perampanel in Combination in Glioma-refractory Epilepsy

Refractory Epilepsy Clinical Trial

Official title: Study of the Efficacy and Safety of Perampanel in Combination in Glioma-refractory Epilepsy

Status Withdrawn

Clinical Trial Summary

Gliomas are primitive brain tumors frequently associated with epilepsy. In a significant number of these patients epilepsy is resistant to antiepileptic drugs. There are currently no recommendations for the management of these drug-resistant epilepsies associated with glioma. In addition, few studies have addressed the subject and no treatment appears to be superior to others in the literature for this indication. In addition, many antiepileptic drugs pose problems of tolerance or interaction with chemotherapy in these patients.

Fundamental studies on glioma-associated epilepsies have shown that there is a major dysregulation of glutamatergic systems involved in epileptogenesis and tumor growth. Targeting this glutamatergic system seems particularly interesting from a physiopathological point of view. Perampanel is a recent antiepileptic treatment with a novel mode of action targeting AMPA glutamate receptors. It has been shown to be effective in patients with drug-resistant epilepsies. He has demonstrated his tolerance in these patients. He has obtained a marketing authorization and is therefore used in routine epileptology without serious problems of tolerance being reported. It is neither an inducer nor an enzyme inhibitor, avoiding the problems of interaction with chemotherapy and is used in a daily dose facilitating compliance.

Therefore, there may be specific antiepileptic efficacy of perampanel in patients with glioma. Nevertheless, the only current data is limited to a retrospective study of 12 patients.

The objective of this protocol is to evaluate the efficacy and safety of perampanel in patients with glioma with drug-resistant epilepsy.

a prospective randomized study with two parallel arms: antiepileptic combination therapy with perampanel and antiepileptic combination therapy without perampanel (free choice of the practitioner). The main criterion of judgment will be the decrease of the monthly frequency of crisis. Secondary endpoints will assess tolerance, efficacy on responder rate (at least 50% decrease in seizure frequency), seizure severity (secondary generalization, loss of consciousness), and quality. patients' lives (quality of life questionnaires, side effects and anxiety / depression). The duration of participation per patient will be 23 weeks (6 weeks of baseline, 5 weeks of titration and 12 weeks of maintenance). The recruitment period will be 3 years. Investigators plan to recruit 120 patients.

In the context of no recommendation in the management of these patients, superior efficacy of perampanel compared with other antiepileptic drugs is expected. This would allow targeted treatment in this population and confirm the tolerance of this treatment in these patients.

Clinical Trial Description

Background: Gliomas are primitive brain tumors frequently associated with epilepsy. In a significant number of these patients epilepsy is resistant to antiepileptic drugs. There are currently no recommendations for the management of these drug-resistant epilepsies associated with glioma. In addition, few studies have addressed the subject and no treatment appears to be superior to others in the literature for this indication. In addition, many antiepileptic drugs pose problems of tolerance or interaction with chemotherapy in these patients.

Rational: Fundamental studies on glioma-associated epilepsies have shown that there is a major dysregulation of glutamatergic systems involved in epileptogenesis (= perpetuation of epileptic seizures) and tumor growth (Huberfeld and Vecht, 2016). Targeting this glutamatergic system seems particularly interesting from a physiopathological point of view. Perampanel is a recent antiepileptic treatment with a novel mode of action targeting AMPA glutamate receptors. It has been shown to be effective in patients with drug-resistant epilepsies. He has demonstrated his tolerance in these patients. He has obtained a marketing authorization and is therefore used in routine epileptology without serious problems of tolerance being reported. It is neither an inducer nor an enzyme inhibitor, avoiding the problems of interaction with chemotherapy and is used in a daily dose facilitating compliance.

Therefore, there may be specific antiepileptic efficacy of perampanel in patients with glioma. Nevertheless, the only current data is limited to a retrospective study of 12 patients.

The objective of this protocol is to evaluate the efficacy and safety of perampanel in patients with glioma with drug-resistant epilepsy.

The investigators want to perform a prospective randomized study with two parallel arms:

antiepileptic combination therapy with perampanel and antiepileptic combination therapy without perampanel (free choice of the practitioner). The main criterion of judgment will be the decrease of the monthly frequency of crisis. Secondary endpoints will assess tolerance, efficacy on responder rate (at least 50% decrease in seizure frequency), seizure severity (secondary generalization, loss of consciousness), and quality. patients' lives (quality of life questionnaires, side effects and anxiety / depression). The duration of participation per patient will be 23 weeks (6 weeks of baseline, 5 weeks of titration and 12 weeks of maintenance). The recruitment period will be 3 years. The investigators plan to recruit 120 patients.

Expected benefits: In the context of no recommendation in the management of these patients, the investigators hope to demonstrate superior efficacy of perampanel compared with other antiepileptic drugs. This would allow targeted treatment in this population and confirm the tolerance of this treatment in these patients. ;

Related Conditions & MeSH terms

• Drug Resistant Epilepsy
• Epilepsy
• Refractory Epilepsy

• NCT number: NCT03636958
• Study type: Interventional
• Source: Assistance Publique Hopitaux De Marseille
• Status: Withdrawn
• Phase: N/A
• Start date: February 15, 2021
• Completion date: December 1, 2026