Efficacy and Safety of Perampanel in Combination in Glioma-refractory Epilepsy
Efficacy and Safety of Perampanel in Combination in Glioma-refractory Epilepsy
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.
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.
Inclusion Criteria:

 Patient, male or female, over 18 years old

 -  Glioma confirmed by histology

 -  Not in progression (clinico-radiological criterion RANO, (Wen et al., 2014), see
 appendix 1)

 -  No clinical worsening (excluding epileptic seizures)

 -  No increase greater than 25% in contrast enhancement after gadolinium injection

 -  No increase in the T2 / FLAIR hyper signal

 -  Absence of new lesion

 -  Diagnosis of drug-resistant epilepsy according to international epilepsy definitions
 (Fisher 2014 and Kwan 2010, see Appendices 2 and 3)

 o Repeated epileptic seizures despite testing of two effective dose antiepileptic
 drugs tried at least 3 months

 -  With at least 2 attacks per month (to ensure visibility on the duration of the study
 of the antiepileptic effect, see below)

 -  Patient with epileptic seizures not limited to only subjective signs

 Exclusion Criteria:

 -  Pregnant or lactating woman

 -  Minor

 -  Impossibility of signing consent

 -  No affiliation to a social security scheme (beneficiary or beneficiary)

 -  Person in emergency,

 -  Person of legal age subject to a legal protection measure (major under guardianship,
 guardianship or court order), or unable to express his or her consent

 -  Patient with at least 2 generalized tonic-clonic seizures per month.