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/NCT06024538</url>
    </required_header>
    <id_info>
      <org_study_id>CHUBX 2023/34</org_study_id>
      <nct_id>NCT06024538</nct_id>
    </id_info>
    <brief_title>Role of Cancer-associated Fibroblast, MDSCs and Immune Cell Interplays in the Resistance of Non-small Cell Lung Cancer to Anti-PD1/PD-L1 Therapies</brief_title>
    <acronym>COCKPI-T</acronym>
    <official_title>Role of Cancer-associated Fibroblast, MDSCs and Immune Cell Interplays in the Resistance of Non-small Cell Lung Cancer to Anti-PD1/PD-L1 Therapies</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Hospital, Bordeaux</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Hospital, Bordeaux</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>
        Immunotherapy have revolutionized the field of oncology, but response rates are low and all&#xD;
        patients relapse, due to cellular and soluble immunosuppressive mechanisms. We want to better&#xD;
        characterize these immunosuppressive mechanisms and their involvement in therapeutic&#xD;
        responses in non-small cell lung cancers (NSCLC). Indeed, we will perform large&#xD;
        transcriptomic analysis of different subsets of immunosuppressive cells, correlating them to&#xD;
        clinical outcome in a cohort of stage III disease, treated by radiochemotherapy and&#xD;
        immunotherapy as maintenance, and stage IV treated by immunotherapy as first-line treatment.&#xD;
        Furthermore, we will analyse cellular mechanisms by in vitro studies, assessing the effect of&#xD;
        immunosuppressive cells, provided by fresh tumor samples, on phenotype and functions of lung&#xD;
        cancer cell lines. The aim of this study is to better characterize immunosuppressive&#xD;
        landscape of NSCLC and mechanisms involved in their protumor functions.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In recent years, immune-based therapies have revolutionized the field of oncology by&#xD;
        significantly improving survival of cancer patients. Despite sustained responses, only 20% to&#xD;
        40% of cancer patients respond. It has become clear that the immunosuppressive environment&#xD;
        induced by tumor through cellular and/or soluble pathways critically contribute to hinder&#xD;
        efficient antitumor immunity. The inhibition of these immunosuppressive networks thus&#xD;
        represents an essential prerequisite for the improvement of responses to anticancer&#xD;
        immunotherapies. Several immune and non -immune cell populations have been identified as key&#xD;
        actors of tumor-induced immunosuppression, among which are myeloid-derived suppressor cells&#xD;
        (MDSC), and cancer associated fibroblasts (CAF). However, in non-small cell lung cancers&#xD;
        (NSCLC), the phenotypic characteristics and the prognostic role of these cells, the&#xD;
        mechanisms underlying their immunosuppressive functions, and their role in dampening the&#xD;
        efficacy of immunotherapies in clinical practice are less characterized. The aim of this&#xD;
        project is to better characterize these different immunosuppressive subpopulations, and to&#xD;
        study their role promoting NSCLC development and resistance to immunotherapies.&#xD;
  &#xD;
        First the tumor CAF and immunosuppressive microenvironment using single cell RNA sequencing&#xD;
        will be characterized (objective 1a). After identification of phenotypic markers, the&#xD;
        immunosuppressive landscape of stage III NSCLC on a lung cancer cohort treated at Bordeaux&#xD;
        University Hospital will be analysed, and data on CAF, MDSC and immune infiltration will be&#xD;
        correlated with tumor characteristics and cancer outcome (objective 1b). Finally, we will&#xD;
        assess in vitro the pro-tumor functions of CAF isolated from lung cancer patients (objective&#xD;
        2).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2024</completion_date>
    <primary_completion_date type="Anticipated">September 2024</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>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Descriptive analysis of immune infiltration and phenotypic and functional characteristics of the different cell subgroups isolated from fresh tumors</measure>
      <time_frame>At the time of surgery only, when fresh tumor is resected</time_frame>
      <description>Exploratory analysis of the immune infiltration (phenotype and function of immunosuppressive and antitumor immune cells) and of the cancer-associated fibroblasts through a transcriptomic analysis of fresh resected lung carcinoma, comparing patients with lymph node involvement or not. Bioinformatics analysis of gene panels</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Correlation between the infiltration of CAF and immunosuppressive immune cells and with clinicopathological parameters and patient prognosis (relapse free-survival, overall survival) in stage III NSCLC exposed to immunotherapy</measure>
      <time_frame>Between September 2018 and December 2021, receiving concomitant radiochemotherapy followed by durvalumab (maintenance)</time_frame>
      <description>Analyze CAF and immunosuppressive immune infiltration in a cohort of unresectable stage III lung carcinoma treated with radiochemotherapy followed by immunotherapy, assessing correlation between immunosuppressive subpopulations and clinical parameters and patient outcome. We will use a multiplexing immunofluorescence assay</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Comparative analysis of the modifications of phenotype and functions of MDSC and T lymphocytes when exposed to CAF extracted from patient tumor tissue</measure>
      <time_frame>At the time of surgery only, when fresh tumor is resected</time_frame>
      <description>Functional in vitro studies of the effect of CAF on phenotype and function of T lymphocytes and of MDSC being extracted from resected NSCLC prospectively collected</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Lung Neoplasm</condition>
    <condition>Cancer Associated Fibroblast</condition>
    <condition>Myeloid-Derived Suppressive Cells Immunosuppression</condition>
    <arm_group>
      <arm_group_label>Prospective part of the study</arm_group_label>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Tumor samples</intervention_name>
      <description>Tumor samples will be collected by the pathologist at the reception of the tumor removed during surgery</description>
      <arm_group_label>Prospective part of the study</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Patients with lung carcinoma surgically treated by surgery only, or stage III lung&#xD;
          carcinoma treated by concomitant radiochemotherapy followed by durvalumab (maintenance)&#xD;
          treated between September 2018 and december 2021&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  consecutive patients&#xD;
  &#xD;
            -  lung carcinoma surgically treated by surgery only (objectives 1a and 2), or stage III&#xD;
               lung carcinoma treated by concomitant radiochemotherapy followed by durvalumab&#xD;
               (maintenance) treated between September 2018 and december 2021 (objective 1b)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  patient receiving chemotherapy, radiotherapy or immunotherapy in the neoadjuvant&#xD;
               setting (all objectives)&#xD;
  &#xD;
            -  patient with previous cancer&#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_contact>
      <last_name>Charlotte DOMBLIDES</last_name>
      <email>charlotte.domblides@chu-bordeaux.fr</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Matthieu THUMEREL</last_name>
      <email>matthieu.thumerel@chu-bordeaux.fr</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>CHU de Bordeaux - Hôpital Saint-André, Service d'Oncologie Médicale</name>
        <address>
          <city>Bordeaux</city>
          <zip>33000</zip>
          <country>France</country>
        </address>
      </facility>
      <contact>
        <last_name>Charlotte DOMBLIDES</last_name>
        <email>charlotte.domblides@chu-bordeaux.fr</email>
      </contact>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Lung cancer</keyword>
    <keyword>Immunosuppression</keyword>
    <keyword>Immunotherapy</keyword>
    <keyword>Immuno-oncology</keyword>
    <keyword>Antitumor immune escape</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>No</sharing_ipd>
    </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/NCT06024538
  org study id: CHUBX 2023/34
  nct id: NCT06024538
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Immunotherapy have revolutionized the field of oncology, but response rates are low and all
        patients relapse, due to cellular and soluble immunosuppressive mechanisms. We want to better
        characterize these immunosuppressive mechanisms and their involvement in therapeutic
        responses in non-small cell lung cancers (NSCLC). Indeed, we will perform large
        transcriptomic analysis of different subsets of immunosuppressive cells, correlating them to
        clinical outcome in a cohort of stage III disease, treated by radiochemotherapy and
        immunotherapy as maintenance, and stage IV treated by immunotherapy as first-line treatment.
        Furthermore, we will analyse cellular mechanisms by in vitro studies, assessing the effect of
        immunosuppressive cells, provided by fresh tumor samples, on phenotype and functions of lung
        cancer cell lines. The aim of this study is to better characterize immunosuppressive
        landscape of NSCLC and mechanisms involved in their protumor functions.
  In recent years, immune-based therapies have revolutionized the field of oncology by
        significantly improving survival of cancer patients. Despite sustained responses, only 20% to
        40% of cancer patients respond. It has become clear that the immunosuppressive environment
        induced by tumor through cellular and/or soluble pathways critically contribute to hinder
        efficient antitumor immunity. The inhibition of these immunosuppressive networks thus
        represents an essential prerequisite for the improvement of responses to anticancer
        immunotherapies. Several immune and non -immune cell populations have been identified as key
        actors of tumor-induced immunosuppression, among which are myeloid-derived suppressor cells
        (MDSC), and cancer associated fibroblasts (CAF). However, in non-small cell lung cancers
        (NSCLC), the phenotypic characteristics and the prognostic role of these cells, the
        mechanisms underlying their immunosuppressive functions, and their role in dampening the
        efficacy of immunotherapies in clinical practice are less characterized. The aim of this
        project is to better characterize these different immunosuppressive subpopulations, and to
        study their role promoting NSCLC development and resistance to immunotherapies.
  
        First the tumor CAF and immunosuppressive microenvironment using single cell RNA sequencing
        will be characterized (objective 1a). After identification of phenotypic markers, the
        immunosuppressive landscape of stage III NSCLC on a lung cancer cohort treated at Bordeaux
        University Hospital will be analysed, and data on CAF, MDSC and immune infiltration will be
        correlated with tumor characteristics and cancer outcome (objective 1b). Finally, we will
        assess in vitro the pro-tumor functions of CAF isolated from lung cancer patients (objective
        2).
  observational model: Cohort
  time perspective: Prospective
  measure: Descriptive analysis of immune infiltration and phenotypic and functional characteristics of the different cell subgroups isolated from fresh tumors
  time frame: At the time of surgery only, when fresh tumor is resected
  description: Exploratory analysis of the immune infiltration (phenotype and function of immunosuppressive and antitumor immune cells) and of the cancer-associated fibroblasts through a transcriptomic analysis of fresh resected lung carcinoma, comparing patients with lymph node involvement or not. Bioinformatics analysis of gene panels
  measure: Correlation between the infiltration of CAF and immunosuppressive immune cells and with clinicopathological parameters and patient prognosis (relapse free-survival, overall survival) in stage III NSCLC exposed to immunotherapy
  time frame: Between September 2018 and December 2021, receiving concomitant radiochemotherapy followed by durvalumab (maintenance)
  description: Analyze CAF and immunosuppressive immune infiltration in a cohort of unresectable stage III lung carcinoma treated with radiochemotherapy followed by immunotherapy, assessing correlation between immunosuppressive subpopulations and clinical parameters and patient outcome. We will use a multiplexing immunofluorescence assay
  measure: Comparative analysis of the modifications of phenotype and functions of MDSC and T lymphocytes when exposed to CAF extracted from patient tumor tissue
  time frame: At the time of surgery only, when fresh tumor is resected
  description: Functional in vitro studies of the effect of CAF on phenotype and function of T lymphocytes and of MDSC being extracted from resected NSCLC prospectively collected
  arm group label: Prospective part of the study
  intervention type: Procedure
  intervention name: Tumor samples
  description: Tumor samples will be collected by the pathologist at the reception of the tumor removed during surgery
  arm group label: Prospective part of the study
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Charlotte DOMBLIDES
  email: charlotte.domblides@chu-bordeaux.fr
  last name: Matthieu THUMEREL
  email: matthieu.thumerel@chu-bordeaux.fr
  facility: 
  contact: 
  country: France
  responsible party type: Sponsor
  mesh term: Lung Neoplasms
  sharing ipd: No