<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04497142</url>
  </required_header>
  <id_info>
    <org_study_id>20-059</org_study_id>
    <secondary_id>2P50CA165962-06A1</secondary_id>
    <nct_id>NCT04497142</nct_id>
  </id_info>
  <brief_title>Effect of Perampanel on Peritumoral Hyperexcitability in HGG</brief_title>
  <official_title>Pilot Study of Perampanel on Peritumoral Hyperexcitability and Seizure Control in Newly Diagnosed High Grade Glioma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eisai Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to learn more about seizures in people with primary&#xD;
      brain tumors. It will evaluate whether an antiseizure medication decreases hyperexcitability&#xD;
      activity around tumors and prevents seizures.&#xD;
&#xD;
      The procedure and study drug involved in this study are:&#xD;
&#xD;
        -  Electrocorticography&#xD;
&#xD;
        -  Perampanel (Fycompa)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is a Pilot Study, which is the first time investigators are examining&#xD;
      brain activity after taking perampanel.&#xD;
&#xD;
      The U.S. Food and Drug Administration (FDA) has approved perampanel as a treatment option for&#xD;
      seizures. It has not been approved for the treatment of brain tumors. Recording of brain&#xD;
      activity (electrocorticography) during surgery is an established clinical procedure, which&#xD;
      will be performed for investigational purposes. This research study is studying brain&#xD;
      recordings and perampanel treatment in participants with brain tumors for the following&#xD;
      reasons:&#xD;
&#xD;
        -  People with brain tumors commonly have seizures.&#xD;
&#xD;
        -  Perampanel was developed as an anti-seizure medication, which works by blocking a&#xD;
           signaling pathway between brain cells, mediated by AMPA receptors.&#xD;
&#xD;
        -  Previous research has shown abnormal brain activity around tumors resulting from&#xD;
           increased AMPA receptor activation.&#xD;
&#xD;
        -  Perampanel is expected to decrease abnormal brain activity and prevent seizures by&#xD;
           blocking AMPA receptor signaling.&#xD;
&#xD;
      This study involves two groups of participants, one group who receives the antiseizure&#xD;
      medication perampanel, and the other group who receives the usual antiseizure medication&#xD;
      (typically levetiracetam) at the time of surgery. Participants have the option to choose&#xD;
      which group to participate if they have a preference.&#xD;
&#xD;
      The research study procedures include screening for eligibility, recording brain activity&#xD;
      during surgery, and study treatment including evaluations and follow up visits. Participants&#xD;
      will receive the study drug for as long as they do not have serious side effects and their&#xD;
      disease does not get worse, up to a maximum of 12 months.&#xD;
&#xD;
      It is expected that about 20 people will take part in this research study.&#xD;
&#xD;
      The National Institute of Health (NIH) is supporting this study by providing funding for the&#xD;
      research. Eisai Inc, a pharmaceutical company, is supporting this research study by providing&#xD;
      the study medication.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 5, 2020</start_date>
  <completion_date type="Actual">May 16, 2023</completion_date>
  <primary_completion_date type="Actual">May 16, 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of high frequency oscillations</measure>
    <time_frame>Peri-operative</time_frame>
    <description>The effect of perampanel on peritumoral hyperexcitability will be measured using intraoperative electrocorticography (ECoG) at the time of initial glioma resection to analyze high frequency oscillations (80-500 Hz). The rate of high frequency oscillations over 10 minutes of recording in the tumor margins will be compared between participants receiving perampanel versus standard of care treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Seizure-free rates</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>The clinical effect of perampanel maintenance therapy on seizure control will be measured by seizure-free rates between the time of initial glioma resection and radiographic tumor progression (up to a maximum of 12 months), and compared to seizure-free rates in participants receiving standard of care treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Glioma, Malignant</condition>
  <condition>Surgery</condition>
  <condition>Seizures</condition>
  <arm_group>
    <arm_group_label>Perampanel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will take a predetermined first dose of perampanel on the day before their tumor surgery&#xD;
During surgery, an approximately 4x6cm recording grid will be placed on the surface of the brain over the tumor, and brain activity around the tumor will be recorded for 10 minutes during surgery (Electrocorticography).&#xD;
After surgery participants will take perampanel at a predetermined dose once a day for as long as they do not have serious side effects and their disease does not get worse, up to a maximum of 12 months. Participants will be provided a drug and seizure diary to document drug and seizure information and have monthly study visits either in clinic or by phone.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive standard of care medication before surgery.&#xD;
During surgery, an approximately 4x6cm recording grid will be placed on the surface of the brain over the tumor, and brain activity around the tumor will be recorded for 10 minutes during surgery (Electrocorticography).&#xD;
After surgery participants will take standard of care medications as predetermined by their doctor. Participants will be provided a drug and seizure diary to document drug and seizure information and have monthly study visits either in clinic or by phone.&#xD;
Participants will be followed up to 12 months after completing surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perampanel</intervention_name>
    <description>Tablet taken orally 1x daily.</description>
    <arm_group_label>Perampanel</arm_group_label>
    <other_name>E2007</other_name>
    <other_name>Fycompa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Predetermined standard of care drug and dosing</description>
    <arm_group_label>Standard of Care</arm_group_label>
    <other_name>Standard treatment (typically the anti-seizure medication levetiracetam)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must have radiologic evidence of anaplastic astrocytoma or glioblastoma&#xD;
             multiforme within 14 days of enrollment.&#xD;
&#xD;
          -  Participants must have measurable disease, defined as at least one lesion that can be&#xD;
             accurately measured in at least one dimension as ≥10 mm (≥1 cm) with CT or MRI. See&#xD;
             Section 11 (Measurement of Effect) for the evaluation of measurable disease.&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).&#xD;
&#xD;
          -  Participants must have adequate organ and marrow function as defined below:&#xD;
&#xD;
               -  absolute neutrophil count ≥1,500/mcL&#xD;
&#xD;
               -  platelets ≥100,000/mcL&#xD;
&#xD;
               -  total bilirubin ≤ institutional upper limit of normal (ULN)&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN&#xD;
&#xD;
               -  glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 (see Appendix B)&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral&#xD;
             therapy with undetectable viral load within 6 months are eligible for this trial.&#xD;
&#xD;
          -  For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV&#xD;
             viral load must be undetectable on suppressive therapy, if indicated.&#xD;
&#xD;
          -  Participants with a history of hepatitis C virus (HCV) infection must have been&#xD;
             treated and cured. For participants with HCV infection who are currently on treatment,&#xD;
             they are eligible if they have an undetectable HCV viral load.&#xD;
&#xD;
          -  Participants with a prior or concurrent malignancy whose natural history or treatment&#xD;
             does not have the potential to interfere with the safety or efficacy assessment of the&#xD;
             investigational regimen are eligible for this trial.&#xD;
&#xD;
          -  Participants with known history or current symptoms of cardiac disease, or history of&#xD;
             treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac&#xD;
             function using the New York Heart Association Functional Classification. To be&#xD;
             eligible for this trial, participants should be class 2B or better.&#xD;
&#xD;
          -  The effects of perampanel on the developing human fetus are unknown. For this reason&#xD;
             and because some anti-seizure medications are known to be teratogenic, women of&#xD;
             childbearing potential and men must agree to use adequate contraception (hormonal or&#xD;
             barrier method of birth control; abstinence) prior to study entry and for the duration&#xD;
             of study participation. Should a woman become pregnant or suspect she is pregnant&#xD;
             while she or her partner is participating in this study, she should inform her&#xD;
             treating physician immediately.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants with brain metastases due to confounding effects on the study objectives.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to perampanel.&#xD;
&#xD;
          -  Participants receiving any medications or substances that are moderate or strong&#xD;
             inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly&#xD;
             changing, it is important to regularly consult a frequently-updated medical reference.&#xD;
             As part of the enrollment/informed consent procedures, the participant will be&#xD;
             counseled on the risk of interactions with other agents, and what to do if new&#xD;
             medications need to be prescribed or if the participant is considering a new&#xD;
             over-the-counter medicine or herbal product.&#xD;
&#xD;
          -  Participants with uncontrolled intercurrent illness.&#xD;
&#xD;
          -  Participants with psychiatric illness/social situations that would limit compliance&#xD;
             with study requirements.&#xD;
&#xD;
          -  Pregnant women are excluded from this study because perampanel is an anti-seizure&#xD;
             agent with the potential for teratogenic or abortifacient effects. Because there is an&#xD;
             unknown but potential risk for adverse events in nursing infants secondary to&#xD;
             treatment of the mother with perampanel, breastfeeding should be discontinued if the&#xD;
             mother is treated with perampanel.&#xD;
&#xD;
          -  Participants with a history of suicide attempt or current active suicidal ideation&#xD;
             with intent as defined by Columbia Suicide Severity Rating Scale (C-SSRS) type 4-5,&#xD;
             due to the potential for suicidal ideation with the use of all anti-seizure&#xD;
             medications.&#xD;
&#xD;
          -  Participants who are unable to swallow pills.&#xD;
&#xD;
          -  Participants with tumor associated seizures greater than one month before planned&#xD;
             surgery.&#xD;
&#xD;
          -  Participants currently receiving treatment with more than one anti-seizure medication.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jong Woo Lee, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>August 9, 2023</last_update_submitted>
  <last_update_submitted_qc>August 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Jong Woo Lee, MD PhD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Glioma</keyword>
  <keyword>Surgery</keyword>
  <keyword>Seizures</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioma</mesh_term>
    <mesh_term>Seizures</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Levetiracetam</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Steven Tobochnik, MD at stobochnik@bwh.harvard.edu. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data can be shared no earlier than 1 year following the date of publication</ipd_time_frame>
    <ipd_access_criteria>BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04497142
org study id: 20-059
secondary id: 2P50CA165962-06A1
nct id: NCT04497142
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this research study is to learn more about seizures in people with primary
      brain tumors. It will evaluate whether an antiseizure medication decreases hyperexcitability
      activity around tumors and prevents seizures.

      The procedure and study drug involved in this study are:

        -  Electrocorticography

        -  Perampanel (Fycompa)
This research study is a Pilot Study, which is the first time investigators are examining
      brain activity after taking perampanel.

      The U.S. Food and Drug Administration (FDA) has approved perampanel as a treatment option for
      seizures. It has not been approved for the treatment of brain tumors. Recording of brain
      activity (electrocorticography) during surgery is an established clinical procedure, which
      will be performed for investigational purposes. This research study is studying brain
      recordings and perampanel treatment in participants with brain tumors for the following
      reasons:

        -  People with brain tumors commonly have seizures.

        -  Perampanel was developed as an anti-seizure medication, which works by blocking a
           signaling pathway between brain cells, mediated by AMPA receptors.

        -  Previous research has shown abnormal brain activity around tumors resulting from
           increased AMPA receptor activation.

        -  Perampanel is expected to decrease abnormal brain activity and prevent seizures by
           blocking AMPA receptor signaling.

      This study involves two groups of participants, one group who receives the antiseizure
      medication perampanel, and the other group who receives the usual antiseizure medication
      (typically levetiracetam) at the time of surgery. Participants have the option to choose
      which group to participate if they have a preference.

      The research study procedures include screening for eligibility, recording brain activity
      during surgery, and study treatment including evaluations and follow up visits. Participants
      will receive the study drug for as long as they do not have serious side effects and their
      disease does not get worse, up to a maximum of 12 months.

      It is expected that about 20 people will take part in this research study.

      The National Institute of Health (NIH) is supporting this study by providing funding for the
      research. Eisai Inc, a pharmaceutical company, is supporting this research study by providing
      the study medication.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of high frequency oscillations
time frame: Peri-operative
description: The effect of perampanel on peritumoral hyperexcitability will be measured using intraoperative electrocorticography (ECoG) at the time of initial glioma resection to analyze high frequency oscillations (80-500 Hz). The rate of high frequency oscillations over 10 minutes of recording in the tumor margins will be compared between participants receiving perampanel versus standard of care treatment.
measure: Seizure-free rates
time frame: Up to 12 months
description: The clinical effect of perampanel maintenance therapy on seizure control will be measured by seizure-free rates between the time of initial glioma resection and radiographic tumor progression (up to a maximum of 12 months), and compared to seizure-free rates in participants receiving standard of care treatment.
arm group label: Perampanel
arm group type: Experimental
description: Participants will take a predetermined first dose of perampanel on the day before their tumor surgery
During surgery, an approximately 4x6cm recording grid will be placed on the surface of the brain over the tumor, and brain activity around the tumor will be recorded for 10 minutes during surgery (Electrocorticography).
After surgery participants will take perampanel at a predetermined dose once a day for as long as they do not have serious side effects and their disease does not get worse, up to a maximum of 12 months. Participants will be provided a drug and seizure diary to document drug and seizure information and have monthly study visits either in clinic or by phone.
arm group label: Standard of Care
arm group type: Active Comparator
description: Participants will receive standard of care medication before surgery.
During surgery, an approximately 4x6cm recording grid will be placed on the surface of the brain over the tumor, and brain activity around the tumor will be recorded for 10 minutes during surgery (Electrocorticography).
After surgery participants will take standard of care medications as predetermined by their doctor. Participants will be provided a drug and seizure diary to document drug and seizure information and have monthly study visits either in clinic or by phone.
Participants will be followed up to 12 months after completing surgery.
intervention type: Drug
intervention name: Perampanel
description: Tablet taken orally 1x daily.
arm group label: Perampanel
other name: E2007
other name: Fycompa
intervention type: Drug
intervention name: Standard of Care
description: Predetermined standard of care drug and dosing
arm group label: Standard of Care
other name: Standard treatment (typically the anti-seizure medication levetiracetam)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jong Woo Lee, MD, PhD
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Jong Woo Lee, MD PhD
investigator title: Principal Investigator
mesh term: Glioma
mesh term: Seizures
mesh term: Levetiracetam
sharing ipd: Yes
ipd description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Steven Tobochnik, MD at stobochnik@bwh.harvard.edu. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data can be shared no earlier than 1 year following the date of publication
ipd access criteria: BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu