xml: <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/NCT05996263</url>
    </required_header>
    <id_info>
      <org_study_id>29BRC23.0142 - PEMBROMIC</org_study_id>
      <nct_id>NCT05996263</nct_id>
    </id_info>
    <brief_title>Prognostic Value of Combined Approach Based on KEAP1/NFE2L2 Mutations and Pre-therapeutic FDG-PET/CT Radiomic Analysis in Advanced Non-small-cell Lung Cancer PDL1 ≥ 50% Treated With Pembrolizumab (PEMBROMIC)</brief_title>
    <acronym>PEMBROMIC</acronym>
    <official_title>Prognostic Value of Combined Approach Based on KEAP1/NFE2L2 Mutations and Pre-therapeutic FDG-PET/CT Radiomic Analysis in Advanced Non-small-cell Lung Cancer PDL1 ≥ 50% Treated With Pembrolizumab.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital, Brest</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Hospital, Brest</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Pembrolizumab has been approved for first-line locally advanced or metastatic NSCLC with a&#xD;
        tumor proportion score (TPS) ≥50% for PDL1, based on the results of KEYNOTE-024.&#xD;
  &#xD;
        However, even with a positive PDL1 status, only a fraction of patients respond to&#xD;
        immunotherapy. In the KEYNOTE-024 study evaluating pembrolizumab versus chemotherapy in&#xD;
        first-line advanced NSCLC with PDL1 TPS ≥50%, the response rate in the pembrolizumab arm&#xD;
        alone was 45%. NFE2L2 is a transcription factor that directs the expression of free radical&#xD;
        defense genes that may interfere with radiation-induced DNA damage. KEAP1 is an adaptor&#xD;
        protein that targets NFE2L2 for ubiquitination and proteasomal destruction as part of normal&#xD;
        homeostasis. These new biomarkers are of clinical interest, as KEAP1/NFE2L2 mutations predict&#xD;
        radiation resistance in patients with localized NSCLC treated with radiotherapy but not&#xD;
        surgery. Some data also suggest a role for the KEAP1/NFE2L2 axis in response to&#xD;
        immunotherapy.&#xD;
  &#xD;
        Establishing a predictive model for the presence of the KEAP1/NFE2L2 mutation would provide a&#xD;
        tool for predicting survival (progression-free and overall), even before the patient starts&#xD;
        immunotherapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Pembrolizumab has been approved for first-line locally advanced or metastatic NSCLC with a&#xD;
        tumor proportion score (TPS) ≥50% for PDL1, based on the results of KEYNOTE-024.&#xD;
  &#xD;
        However, even with a positive PDL1 status, only a fraction of patients respond to&#xD;
        immunotherapy. In the KEYNOTE-024 study evaluating pembrolizumab versus chemotherapy in&#xD;
        first-line advanced NSCLC with PDL1 TPS ≥50%, the response rate in the pembrolizumab arm&#xD;
        alone was 45%. This result led to the approval of pembrolizumab for first-line advanced NSCLC&#xD;
        with PDL1 TPS ≥ 50%, which nevertheless represents only 22% of patients with stage IIIB/IV&#xD;
        NSCLC.&#xD;
  &#xD;
        Early identification of biomarkers for patients unlikely to benefit from first-line&#xD;
        pembrolizumab is therefore a crucial step in selecting suitable candidates.&#xD;
  &#xD;
        Furthermore, in cancer, genomic alterations in NFE2L2, KEAP1 and CUL3 result in constitutive&#xD;
        activation of NRF2-dependent gene transcription, which promotes cellular resistance to&#xD;
        oxidative stress, xenobiotic efflux, proliferation and metabolic reprogramming. Somatic&#xD;
        mutations in NFE2L2 and KEAP1 are found in 3.5-15% and 12-17% of NSCLC patients respectively.&#xD;
        NFE2L2 is a transcription factor that directs the expression of free radical defense genes&#xD;
        that may interfere with radiation-induced DNA damage. KEAP1 is an adaptor protein that&#xD;
        targets NFE2L2 for ubiquitination and proteasomal destruction as part of normal homeostasis.&#xD;
        These new biomarkers are of clinical interest, as KEAP1/NFE2L2 mutations predict radiation&#xD;
        resistance in patients with localized NSCLC treated with radiotherapy but not surgery. Some&#xD;
        data also suggest a role for the KEAP1/NFE2L2 axis in response to immunotherapy.&#xD;
  &#xD;
        Establishing a predictive model for the presence of the KEAP1/NFE2L2 mutation would provide a&#xD;
        tool for predicting survival (progression-free and overall), even before the patient starts&#xD;
        immunotherapy.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 1, 2023</start_date>
    <completion_date type="Anticipated">August 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">August 31, 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Progression-Free survival (PFS)</measure>
      <time_frame>through study completion, an average of 1 year</time_frame>
      <description>PFS is defined as the time elapsed between initiation of treatment and tumor progression or death from any cause.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>through study completion, an average of 1 year</time_frame>
      <description>OS is defined as the time elapsed between initiation of treatment and death, whatever the cause.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Robustness of the prediction model</measure>
      <time_frame>through study completion, an average of 1 year</time_frame>
      <description>Robustness will be assessed by comparing predictions obtained from 2 different blind reviewers</description>
    </other_outcome>
    <enrollment type="Anticipated">75</enrollment>
    <condition>Lung Cancer Stage III</condition>
    <condition>Lung Cancer Stage IV</condition>
    <eligibility>
      <study_pop>
        <textblock>
          Patients treated or being treated with immunotherapy alone with pembrolizumab in 1st-line&#xD;
          metastatic NSCLC.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age ≥ 18 years&#xD;
  &#xD;
            -  Histologically or cytologically proven non-small-cell lung cancer (NSCLC)&#xD;
  &#xD;
            -  Stage IV NSCLC. Stage III NSCLC unresectable and not amenable to radiotherapy&#xD;
  &#xD;
            -  PD-L1 expression ≥ 50%.&#xD;
  &#xD;
            -  No previous systemic treatment for NSCLC.&#xD;
  &#xD;
            -  Patients treated for 1st-line metastatic disease with immunotherapy alone&#xD;
               (pembrolizumab)&#xD;
  &#xD;
            -  No opposition expressed&#xD;
  &#xD;
            -  Patient affiliated to a social security scheme&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  PD-L1 expression &lt;50&#xD;
  &#xD;
            -  Neuroendocrine tumors&#xD;
  &#xD;
            -  Secondarily metastatic patients&#xD;
  &#xD;
            -  Previous treatments&#xD;
  &#xD;
            -  Opposition formulated&#xD;
  &#xD;
            -  Patient under legal protection (guardianship, curatorship, etc.)&#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>Vincent BOURBONNE, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Radiation Oncology Department, Brest University Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Vincent BOURBONNE, MD, PhD</last_name>
      <phone>+33298223398</phone>
      <email>vincent.bourbonne@chu-brest.fr</email>
    </overall_contact>
    <location>
      <facility>
        <name>Chu Brest</name>
        <address>
          <city>Brest</city>
          <zip>29609</zip>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Vincent BOURBONNE, MD, PhD</last_name>
        <phone>+33298223398</phone>
        <email>vincent.bourbonne@chu-brest.fr</email>
      </contact>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 18, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>PDL1</keyword>
    <keyword>PET/CT</keyword>
    <keyword>Pembrolizumab</keyword>
    <keyword>KEAP1/NFE2L2</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lung Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>All collected data that underlie results in a publication</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_time_frame>Data will be available beginning three years and ending fifteen years following the final study report completion</ipd_time_frame>
      <ipd_access_criteria>Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05996263
  org study id: 29BRC23.0142 - PEMBROMIC
  nct id: NCT05996263
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Pembrolizumab has been approved for first-line locally advanced or metastatic NSCLC with a
        tumor proportion score (TPS) ≥50% for PDL1, based on the results of KEYNOTE-024.
  
        However, even with a positive PDL1 status, only a fraction of patients respond to
        immunotherapy. In the KEYNOTE-024 study evaluating pembrolizumab versus chemotherapy in
        first-line advanced NSCLC with PDL1 TPS ≥50%, the response rate in the pembrolizumab arm
        alone was 45%. NFE2L2 is a transcription factor that directs the expression of free radical
        defense genes that may interfere with radiation-induced DNA damage. KEAP1 is an adaptor
        protein that targets NFE2L2 for ubiquitination and proteasomal destruction as part of normal
        homeostasis. These new biomarkers are of clinical interest, as KEAP1/NFE2L2 mutations predict
        radiation resistance in patients with localized NSCLC treated with radiotherapy but not
        surgery. Some data also suggest a role for the KEAP1/NFE2L2 axis in response to
        immunotherapy.
  
        Establishing a predictive model for the presence of the KEAP1/NFE2L2 mutation would provide a
        tool for predicting survival (progression-free and overall), even before the patient starts
        immunotherapy.
  Pembrolizumab has been approved for first-line locally advanced or metastatic NSCLC with a
        tumor proportion score (TPS) ≥50% for PDL1, based on the results of KEYNOTE-024.
  
        However, even with a positive PDL1 status, only a fraction of patients respond to
        immunotherapy. In the KEYNOTE-024 study evaluating pembrolizumab versus chemotherapy in
        first-line advanced NSCLC with PDL1 TPS ≥50%, the response rate in the pembrolizumab arm
        alone was 45%. This result led to the approval of pembrolizumab for first-line advanced NSCLC
        with PDL1 TPS ≥ 50%, which nevertheless represents only 22% of patients with stage IIIB/IV
        NSCLC.
  
        Early identification of biomarkers for patients unlikely to benefit from first-line
        pembrolizumab is therefore a crucial step in selecting suitable candidates.
  
        Furthermore, in cancer, genomic alterations in NFE2L2, KEAP1 and CUL3 result in constitutive
        activation of NRF2-dependent gene transcription, which promotes cellular resistance to
        oxidative stress, xenobiotic efflux, proliferation and metabolic reprogramming. Somatic
        mutations in NFE2L2 and KEAP1 are found in 3.5-15% and 12-17% of NSCLC patients respectively.
        NFE2L2 is a transcription factor that directs the expression of free radical defense genes
        that may interfere with radiation-induced DNA damage. KEAP1 is an adaptor protein that
        targets NFE2L2 for ubiquitination and proteasomal destruction as part of normal homeostasis.
        These new biomarkers are of clinical interest, as KEAP1/NFE2L2 mutations predict radiation
        resistance in patients with localized NSCLC treated with radiotherapy but not surgery. Some
        data also suggest a role for the KEAP1/NFE2L2 axis in response to immunotherapy.
  
        Establishing a predictive model for the presence of the KEAP1/NFE2L2 mutation would provide a
        tool for predicting survival (progression-free and overall), even before the patient starts
        immunotherapy.
  observational model: Cohort
  time perspective: Retrospective
  measure: Progression-Free survival (PFS)
  time frame: through study completion, an average of 1 year
  description: PFS is defined as the time elapsed between initiation of treatment and tumor progression or death from any cause.
  measure: Overall Survival (OS)
  time frame: through study completion, an average of 1 year
  description: OS is defined as the time elapsed between initiation of treatment and death, whatever the cause.
  measure: Robustness of the prediction model
  time frame: through study completion, an average of 1 year
  description: Robustness will be assessed by comparing predictions obtained from 2 different blind reviewers
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Vincent BOURBONNE, MD, PhD
  role: Principal Investigator
  affiliation: Radiation Oncology Department, Brest University Hospital
  last name: Vincent BOURBONNE, MD, PhD
  phone: +33298223398
  email: vincent.bourbonne@chu-brest.fr
  facility: 
  status: Recruiting
  contact: 
  country: France
  responsible party type: Sponsor
  mesh term: Lung Neoplasms
  sharing ipd: Yes
  ipd description: All collected data that underlie results in a publication
  ipd info type: Study Protocol
  ipd time frame: Data will be available beginning three years and ending fifteen years following the final study report completion
  ipd access criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement