<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/NCT03265496</url>
  </required_header>
  <id_info>
    <org_study_id>CONCORDE-1510</org_study_id>
    <nct_id>NCT03265496</nct_id>
  </id_info>
  <brief_title>Correlation Between Tissue and Plasmatic EGFR in CBNPC With EGFR Mutation or Predictive Factor of EGFR Mutation</brief_title>
  <acronym>CONCORDE</acronym>
  <official_title>Correlation Between Tissue and Plasmatic EGFR in CBNPC With EGFR Mutation or Predictive Factor of EGFR Mutation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Oscar Lambret</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre Oscar Lambret</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Condorde main objective is to evaluate the correlation between EGFR mutational status&#xD;
      determined after tumor biopsy and EGFR mutational status analyzed on ctDNA after liquid&#xD;
      biopsy. EGFR status will be assessed by real time PCR (rtPCR), digital PCR (dPCR) and Next&#xD;
      Generation Sequencing (NGS) in patients with chemotherapy naive lung carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Newest therapeutic breakthrough are often based on molecular analysis of tumoral tissue&#xD;
      before treatment initiation or after emergence of resistance. Tumoral tissue is commonly&#xD;
      obtained by biopsy. However, tumor biopsy is an invasive, scarcely repeatable and costly&#xD;
      technics. Moreover, tumor samples, obtained by biopsy, doesn't represent tumor heterogeneity&#xD;
      and cannot inform about tumor evolution over time.&#xD;
&#xD;
      Recent improvement have been done in detection and characterization of blood circulating&#xD;
      tumoral DNA (ctDNA). ctDNA reach regularly the blood stream after tumoral cell apoptosis or&#xD;
      necrosis and could be extract and sequenced by some molecular biology technics such as real&#xD;
      time PCR (rtPCR), digital PCR (dPCR) or next generation sequencing (NGS). Interesting,&#xD;
      Several studies demonstrate that some genomic alterations of solid cancer can be&#xD;
      characterized after sequencing of ctDNA. Other experiments pointed that ctDNA level could be&#xD;
      linked to tumor stage and patient prognostic.&#xD;
&#xD;
      These progress lead to the development of a new non invasive method for extraction of ctDNA&#xD;
      called liquid biopsy (LB). LB could be useful for monitor tumoral genotype, assess tumor&#xD;
      response to treatment and detect residual tumor cells after curative treatment. Moreover LB&#xD;
      could be an essential method for study of tumor cells molecular alterations mechanisms during&#xD;
      targeted cancer therapies, when clinical resistance occurs.&#xD;
&#xD;
      Non-small cell lung cancer (NSCLC) is the most frequently diagnosticated type of lung cancer.&#xD;
      Regular first line chemotherapy is based on the use of platinum salts. However, some&#xD;
      mutations in the EGFR gene could add sensitivity of NSCLC to tyrosine kinase inhibitors such&#xD;
      as gefitinib, erlotinib or afatinib. Consequently, the search for molecular mutations in&#xD;
      genome of NSCLC cells is of prior interest for patients with clinically advanced NSCLC.&#xD;
&#xD;
      Recently, some studies demonstrate that mutational EGFR status of NSCLC was sharply&#xD;
      correlated between tumoral tissue, obtained by classical biopsy, and ctDNA, collected by&#xD;
      liquid biopsy.&#xD;
&#xD;
      These results provide promising data encouraging the use of LB for study of NSCLC ctDNA.&#xD;
      However some experimentations are needed to ensure these data.&#xD;
&#xD;
      For that reason, CONCORDE clinical trial will evaluate the correlation between EGFR&#xD;
      mutational status determined after tumor biopsy and EGFR mutational status analyzed after&#xD;
      liquid biopsy. EGFR status will be assessed by real time PCR (rtPCR), digital PCR (dPCR) and&#xD;
      Next Generation Sequencing (NGS) in patients with chemotherapy naive lung carcinoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The number of recruted patient was not sufficient&#xD;
  </why_stopped>
  <start_date type="Actual">July 7, 2016</start_date>
  <completion_date type="Actual">April 13, 2021</completion_date>
  <primary_completion_date type="Actual">April 13, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At diagnostic. NGS.</measure>
    <time_frame>Baseline</time_frame>
    <description>For patient with mutant EGFR. Evaluate, by next generation sequencing at diagnostic, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At diagnostic. rtPCR.</measure>
    <time_frame>Baseline</time_frame>
    <description>For patient with mutant EGFR. Evaluate, by real time PCR at diagnostic, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At diagnostic. dPCR.</measure>
    <time_frame>Baseline</time_frame>
    <description>For patient with mutant EGFR. Evaluate, by digital PCR at diagnostic, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At disease progression. NGS.</measure>
    <time_frame>From Baseline to disease progression, up to 2 years</time_frame>
    <description>For patient with mutant EGFR. Evaluate, by Next Generation Sequencing at disease progression, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At disease progression. rtPCR.</measure>
    <time_frame>From Baseline to disease progression, up to 2 years</time_frame>
    <description>For patient with mutant EGFR. Evaluate, by rtPCR at disease progression, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At disease progression. dPCR.</measure>
    <time_frame>From Baseline to disease progression, up to 2 years</time_frame>
    <description>For patient with mutant EGFR. Evaluate, by dPCR at disease progression, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of oncogenic mutation for patients with predictive factors</measure>
    <time_frame>From Baseline to disease progression, up to 2 years</time_frame>
    <description>To evaluate the incidence of oncogenic mutations in populations with clinical predictive factors of these mutations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predictive value of ctDNA during treatment with EGFR targeting therapy.</measure>
    <time_frame>From Baseline to disease progression, up to 2 years</time_frame>
    <description>To assess the predictive value of mutant ctDNA during treatment with EGFR targeting therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mutations on ctDNA and tumor biopsy.</measure>
    <time_frame>From Baseline to disease progression, up to 2 years</time_frame>
    <description>To search for mutations leading to treatment resistance on ctDNA and tumor biopsy at proved disease progression</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Mutation in ctDNA</measure>
    <time_frame>From Baseline to disease progression, up to 2 years</time_frame>
    <description>To detect, at early stage, mutations on liquid biopsy. To identify, at early stage, mutations leading to treatment resistance by Next Generation Sequencing.</description>
  </other_outcome>
  <other_outcome>
    <measure>expression pattern of tumor grade and resistance</measure>
    <time_frame>From Baseline to disease progression, up to 2 years</time_frame>
    <description>To identify a predictive expression pattern for grade and treatment resistance of tumor by iterative sampling during treatment</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Nsclc</condition>
  <arm_group>
    <arm_group_label>study procedure</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Clinical exam. Liquid biopsy. Diagnostic exam (biopsy and imagery). 1st line treatment. tumor evaluation. Biopsy</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Clinical exam</intervention_name>
    <description>Clinical exam is performed before treatment start</description>
    <arm_group_label>study procedure</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Liquid biopsy</intervention_name>
    <description>Liquid biopsy will be performed at baseline and every 3 cycles of chemotherapy until progression disease</description>
    <arm_group_label>study procedure</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Diagnostic exam</intervention_name>
    <description>Diagnostic exam (biopsy and imagery exam) will be performed at baseline if not previously done or incompletely done.</description>
    <arm_group_label>study procedure</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>1st line treatment</intervention_name>
    <description>1st line chemotherapy (chemotherapy or EGFR targeted therapy) will be performed until progression disease.</description>
    <arm_group_label>study procedure</arm_group_label>
    <other_name>1st line chemotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>tumor evaluation</intervention_name>
    <description>Tumor evaluation will be performed every 3 cycles of chemotherapy</description>
    <arm_group_label>study procedure</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Biopsy</intervention_name>
    <description>Biopsy will be performed at the end of study, after progression disease, if a mutation of EGFR is detected in tumor DNA.</description>
    <arm_group_label>study procedure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At least 18 years&#xD;
&#xD;
          -  Metastatic lung carcinoma&#xD;
&#xD;
          -  With: - EGFR gene mutation&#xD;
&#xD;
          -  Or at least 2 predictive factors of addictive mutation (Women, non smocking or&#xD;
             cessation &gt; 3 years, Asiatic, lung adenocarcinoma)&#xD;
&#xD;
          -  Eligible for 1st line treatment&#xD;
&#xD;
          -  Performance status ≤ 3&#xD;
&#xD;
          -  Available tumor sample or tumor reachable for biopsy&#xD;
&#xD;
          -  With informed and signed consent&#xD;
&#xD;
          -  Affiliation to the National Social Security System&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous radiotherapy treatment in months preceding initials samples&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Patient not able to give consent or unwilling to provide consent&#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>Kotecki Nuria, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Oscar Lambret</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Cortot Alexis, Pr</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHRU Lille</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre Oscar Lambret</name>
      <address>
        <city>Lille</city>
        <zip>59020</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Lille</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>October 14, 2021</last_update_submitted>
  <last_update_submitted_qc>October 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03265496
org study id: CONCORDE-1510
nct id: NCT03265496
lead sponsor: 
collaborator: 
has dmc: No
Condorde main objective is to evaluate the correlation between EGFR mutational status
      determined after tumor biopsy and EGFR mutational status analyzed on ctDNA after liquid
      biopsy. EGFR status will be assessed by real time PCR (rtPCR), digital PCR (dPCR) and Next
      Generation Sequencing (NGS) in patients with chemotherapy naive lung carcinoma.
Newest therapeutic breakthrough are often based on molecular analysis of tumoral tissue
      before treatment initiation or after emergence of resistance. Tumoral tissue is commonly
      obtained by biopsy. However, tumor biopsy is an invasive, scarcely repeatable and costly
      technics. Moreover, tumor samples, obtained by biopsy, doesn't represent tumor heterogeneity
      and cannot inform about tumor evolution over time.

      Recent improvement have been done in detection and characterization of blood circulating
      tumoral DNA (ctDNA). ctDNA reach regularly the blood stream after tumoral cell apoptosis or
      necrosis and could be extract and sequenced by some molecular biology technics such as real
      time PCR (rtPCR), digital PCR (dPCR) or next generation sequencing (NGS). Interesting,
      Several studies demonstrate that some genomic alterations of solid cancer can be
      characterized after sequencing of ctDNA. Other experiments pointed that ctDNA level could be
      linked to tumor stage and patient prognostic.

      These progress lead to the development of a new non invasive method for extraction of ctDNA
      called liquid biopsy (LB). LB could be useful for monitor tumoral genotype, assess tumor
      response to treatment and detect residual tumor cells after curative treatment. Moreover LB
      could be an essential method for study of tumor cells molecular alterations mechanisms during
      targeted cancer therapies, when clinical resistance occurs.

      Non-small cell lung cancer (NSCLC) is the most frequently diagnosticated type of lung cancer.
      Regular first line chemotherapy is based on the use of platinum salts. However, some
      mutations in the EGFR gene could add sensitivity of NSCLC to tyrosine kinase inhibitors such
      as gefitinib, erlotinib or afatinib. Consequently, the search for molecular mutations in
      genome of NSCLC cells is of prior interest for patients with clinically advanced NSCLC.

      Recently, some studies demonstrate that mutational EGFR status of NSCLC was sharply
      correlated between tumoral tissue, obtained by classical biopsy, and ctDNA, collected by
      liquid biopsy.

      These results provide promising data encouraging the use of LB for study of NSCLC ctDNA.
      However some experimentations are needed to ensure these data.

      For that reason, CONCORDE clinical trial will evaluate the correlation between EGFR
      mutational status determined after tumor biopsy and EGFR mutational status analyzed after
      liquid biopsy. EGFR status will be assessed by real time PCR (rtPCR), digital PCR (dPCR) and
      Next Generation Sequencing (NGS) in patients with chemotherapy naive lung carcinoma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At diagnostic. NGS.
time frame: Baseline
description: For patient with mutant EGFR. Evaluate, by next generation sequencing at diagnostic, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy.
measure: Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At diagnostic. rtPCR.
time frame: Baseline
description: For patient with mutant EGFR. Evaluate, by real time PCR at diagnostic, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy.
measure: Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At diagnostic. dPCR.
time frame: Baseline
description: For patient with mutant EGFR. Evaluate, by digital PCR at diagnostic, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy.
measure: Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At disease progression. NGS.
time frame: From Baseline to disease progression, up to 2 years
description: For patient with mutant EGFR. Evaluate, by Next Generation Sequencing at disease progression, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy.
measure: Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At disease progression. rtPCR.
time frame: From Baseline to disease progression, up to 2 years
description: For patient with mutant EGFR. Evaluate, by rtPCR at disease progression, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy.
measure: Correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy. At disease progression. dPCR.
time frame: From Baseline to disease progression, up to 2 years
description: For patient with mutant EGFR. Evaluate, by dPCR at disease progression, the correlation between EGFR mutational status determined after tumor biopsy and EGFR mutational status analyzed after liquid biopsy.
measure: Incidence of oncogenic mutation for patients with predictive factors
time frame: From Baseline to disease progression, up to 2 years
description: To evaluate the incidence of oncogenic mutations in populations with clinical predictive factors of these mutations.
measure: Predictive value of ctDNA during treatment with EGFR targeting therapy.
time frame: From Baseline to disease progression, up to 2 years
description: To assess the predictive value of mutant ctDNA during treatment with EGFR targeting therapy.
measure: Mutations on ctDNA and tumor biopsy.
time frame: From Baseline to disease progression, up to 2 years
description: To search for mutations leading to treatment resistance on ctDNA and tumor biopsy at proved disease progression
measure: Mutation in ctDNA
time frame: From Baseline to disease progression, up to 2 years
description: To detect, at early stage, mutations on liquid biopsy. To identify, at early stage, mutations leading to treatment resistance by Next Generation Sequencing.
measure: expression pattern of tumor grade and resistance
time frame: From Baseline to disease progression, up to 2 years
description: To identify a predictive expression pattern for grade and treatment resistance of tumor by iterative sampling during treatment
arm group label: study procedure
arm group type: Experimental
description: Clinical exam. Liquid biopsy. Diagnostic exam (biopsy and imagery). 1st line treatment. tumor evaluation. Biopsy
intervention type: Procedure
intervention name: Clinical exam
description: Clinical exam is performed before treatment start
arm group label: study procedure
intervention type: Procedure
intervention name: Liquid biopsy
description: Liquid biopsy will be performed at baseline and every 3 cycles of chemotherapy until progression disease
arm group label: study procedure
intervention type: Procedure
intervention name: Diagnostic exam
description: Diagnostic exam (biopsy and imagery exam) will be performed at baseline if not previously done or incompletely done.
arm group label: study procedure
intervention type: Drug
intervention name: 1st line treatment
description: 1st line chemotherapy (chemotherapy or EGFR targeted therapy) will be performed until progression disease.
arm group label: study procedure
other name: 1st line chemotherapy
intervention type: Procedure
intervention name: tumor evaluation
description: Tumor evaluation will be performed every 3 cycles of chemotherapy
arm group label: study procedure
intervention type: Biological
intervention name: Biopsy
description: Biopsy will be performed at the end of study, after progression disease, if a mutation of EGFR is detected in tumor DNA.
arm group label: study procedure
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kotecki Nuria, MD
role: Principal Investigator
affiliation: Centre Oscar Lambret
last name: Cortot Alexis, Pr
role: Principal Investigator
affiliation: CHRU Lille
facility: 
facility: 
country: France
responsible party type: Sponsor
sharing ipd: No