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Trial record 90 of 107 for:    PHENYTOIN

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

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ClinicalTrials.gov Identifier: NCT03636958
Recruitment Status : Not yet recruiting
First Posted : August 17, 2018
Last Update Posted : August 17, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique Hopitaux De Marseille

Tracking Information
First Submitted Date  ICMJE August 16, 2018
First Posted Date  ICMJE August 17, 2018
Last Update Posted Date August 17, 2018
Estimated Study Start Date  ICMJE January 2019
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2018)
  • Numbers of crisis at baseline [ Time Frame: 6 weeks ]
    The monthly frequency of crisis
  • Numbers of crisis under treatment [ Time Frame: 5 weeks ]
    The monthly frequency of crisis during treatment period
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Perampanel in Combination in Glioma-refractory Epilepsy
Official Title  ICMJE Study of the Efficacy and Safety of Perampanel in Combination in Glioma-refractory Epilepsy
Brief 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.

Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Refractory Epilepsy
Intervention  ICMJE
  • Drug: Perampanel
    Perampanel is an antiepileptic with a novel mechanism of action as it targets post-synaptic AMPA receptors. It has been shown to be effective as adjunctive therapy (dual therapy) for partial / focal epilepsy seizures and generalized in patients over 12 years of age.
  • Drug: conventional antiepileptic treatment
    choice of the molecule is left to the discretion of the clinician excluding the following benzodiazepines: clobazam, clonazepam, diazepam. Antiepileptic drugs allowed are therefore: lamotrigine, levetiracetam, lacosamide, sodium valproate, carbamazepine, oxcarbabazepine, slicarbazepine, pregabalin, gabapentin, topiramate, phenytoin, phenobarbital, zonisamide, vigabatrin.
Study Arms  ICMJE
  • Active Comparator: control group
    they will receive conventional antiepileptic treatment (antiepileptic combination therapy) without perampanel
    Intervention: Drug: conventional antiepileptic treatment
  • Experimental: experimental group
    they will receive conventional antiepileptic treatment (antiepileptic combination therapy) with perampanel
    Interventions:
    • Drug: Perampanel
    • Drug: conventional antiepileptic treatment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 16, 2018)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: stanislas lagarde, md +33 491385554 Stanislas.LAGARDE@ap-hm.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03636958
Other Study ID Numbers  ICMJE 2018-13
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique Hopitaux De Marseille
Study Sponsor  ICMJE Assistance Publique Hopitaux De Marseille
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: EMILIE GARRIDO PRADALIE APHM
PRS Account Assistance Publique Hopitaux De Marseille
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP