<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/NCT04487457</url>
  </required_header>
  <id_info>
    <org_study_id>RIPH3-RNI20 / CINECI</org_study_id>
    <secondary_id>2020-A01478-31</secondary_id>
    <nct_id>NCT04487457</nct_id>
  </id_info>
  <brief_title>Prospective Study to Evaluate the Blood Kinetics of Immune Cells and Immunosuppressive Cytokines After Exposure to an Immunity Checkpoint Inhibitor (ICI): Study of the Impact of Chemotherapy</brief_title>
  <acronym>CINECI</acronym>
  <official_title>Étude Prospective d'évaluation de la cinétique Sanguine de Cellules Immunitaires et de Cytokines Immunosuppressives après Exposition à un Inhibiteur Des Checkpoints de l'immunité (ICI) : étude de l'Impact de la chimiothérapie</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Tours</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Tours</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>
      Non-small cell lung cancer (NSCLC) is the most common histological form, accounting for 85%&#xD;
      of all bronchopulmonary cancers (PBC). The advent of Immunity Checkpoint Inhibitors (ICIs)&#xD;
      targeting Programmed cell Death-1 (PD-1) is changing current treatment algorithms.&#xD;
&#xD;
      Preliminary results from work carried out in the Medical Oncology Department of the&#xD;
      University Hospital of Tours suggest that immunotherapy targeting ICI, when administered&#xD;
      beforehand, increases the effect of catch-up chemotherapy. In NSCLC, the progression-free&#xD;
      survival (PFS) of 3rd line chemotherapy after anti-PD-1 immunotherapy was better than the PFS&#xD;
      of 3rd line chemotherapy performed at the end of conventional chemotherapy. Moreover, the&#xD;
      combination of chemotherapy and immunotherapy gives paradoxically better results than&#xD;
      immunotherapy alone.&#xD;
&#xD;
      Immunotherapy restores the anti-tumor T immunity inhibited by the cancer cell. While the mode&#xD;
      of action of ICIs is well known, the mechanisms of resistance to them are poorly understood.&#xD;
      Several pathways are evoked, in particular the modulation of cellular interactions within the&#xD;
      tumour microenvironment (TME), the molecular expression profile of cancer cells, or the&#xD;
      immunological status of the patient.&#xD;
&#xD;
      Regulatory T lymphocytes (Treg) participate in the maintenance of immune system homeostasis&#xD;
      by ensuring tolerance to self antigens. Within TME, Treg inhibit anti-tumor T cell activity&#xD;
      and potentiate tumor proliferation. The latter, by specifically recognizing tumor antigens,&#xD;
      block the activity of effector T lymphocytes directed against tumor cells. Thus, an increase&#xD;
      in circulating Treg concentrations and in TME is a poor prognostic factor, especially in&#xD;
      NSCLC.&#xD;
&#xD;
      Gemcitabine chemotherapy is commonly used in the management of NSCLC. Recent data show that&#xD;
      gemcitabine decreases Treg activity and regulates levels of anti-inflammatory TME cytokines&#xD;
      such as IL10, TGF-β and interferon-Ɣ.&#xD;
&#xD;
      The hypothesis of this study is that the decrease in Treg blood concentration by catch-up&#xD;
      chemotherapy restores sensitivity to immunotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Non-small cell lung cancer (NSCLC) is the most common histological form, accounting for 85%&#xD;
      of all bronchopulmonary cancers (PBC). The advent of Immunity Checkpoint Inhibitors (ICIs)&#xD;
      targeting Programmed cell Death-1 (PD-1) is changing current treatment algorithms.&#xD;
&#xD;
      Preliminary results from work carried out in the Medical Oncology Department of the&#xD;
      University Hospital of Tours suggest that immunotherapy targeting ICI, when administered&#xD;
      beforehand, increases the effect of catch-up chemotherapy. In NSCLC, the the progression-free&#xD;
      survival (PFS) of 3rd line chemotherapy after anti-PD-1 immunotherapy was better than the PFS&#xD;
      of 3rd line chemotherapy performed at the end of conventional chemotherapy. Moreover, the&#xD;
      combination of chemotherapy and immunotherapy gives paradoxically better results than&#xD;
      immunotherapy alone.&#xD;
&#xD;
      Immunotherapy restores the anti-tumor T immunity inhibited by the cancer cell. While the mode&#xD;
      of action of ICIs is well known, the mechanisms of resistance to them are poorly understood.&#xD;
      Several pathways are evoked, in particular the modulation of cellular interactions within the&#xD;
      tumour microenvironment (TME), the molecular expression profile of cancer cells, or the&#xD;
      immunological status of the patient.&#xD;
&#xD;
      Regulatory T lymphocytes (Treg) participate in the maintenance of immune system homeostasis&#xD;
      by ensuring tolerance to self antigens. Within TME, Treg inhibit anti-tumor T cell activity&#xD;
      and potentiate tumor proliferation. The latter, by specifically recognizing tumor antigens,&#xD;
      block the activity of effector T lymphocytes directed against tumor cells. Thus, an increase&#xD;
      in circulating Treg concentrations and in TME is a poor prognostic factor, especially in&#xD;
      NSCLC.&#xD;
&#xD;
      Gemcitabine chemotherapy is commonly used in the management of NSCLC. Recent data show that&#xD;
      gemcitabine decreases Treg activity and regulates levels of anti-inflammatory TME cytokines&#xD;
      such as IL10, TGF-β and interferon-Ɣ.&#xD;
&#xD;
      The hypothesis of this study is that the decrease in Treg blood concentration by catch-up&#xD;
      chemotherapy restores sensitivity to immunotherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 3, 2021</start_date>
  <completion_date type="Actual">September 29, 2022</completion_date>
  <primary_completion_date type="Actual">September 29, 2022</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>Change from baseline blood concentration of regulatory T-lymphocytes (Treg) at 6 months</measure>
    <time_frame>Baseline, 3 months and 6 months</time_frame>
    <description>Blood concentrations will be measured at specific times</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline blood concentration of lymphocyte populations T, B, NK, CD4+ and CD8+ (effector T-lymphocytes (Teff) included) at 6 months</measure>
    <time_frame>Baseline, 3 months and 6 months</time_frame>
    <description>Blood concentrations will be measured at specific times</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline blood concentration of anti-inflammatory cytokines at 6 months</measure>
    <time_frame>Baseline, 3 months and 6 months</time_frame>
    <description>Blood concentrations will be measured at specific times</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess correlation between blood concentration of Treg, blood concentration of Teff and blood concentration of anti-inflammatory cytokines</measure>
    <time_frame>Baseline, 3 months and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determination of PDL1 status</measure>
    <time_frame>Baseline</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">31</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <condition>Bladder Cancer</condition>
  <condition>ENT Cancer</condition>
  <arm_group>
    <arm_group_label>Cancer</arm_group_label>
    <description>Patients receiving chemotherapy alone after immunotherapy for NSCLC or bladder cancer or ENT cancer</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood samples</intervention_name>
    <description>Blood samples</description>
    <arm_group_label>Cancer</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study population is patients receiving chemotherapy alone after immunotherapy for NSCLC&#xD;
        or bladder cancer or ENT cancer.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years old&#xD;
&#xD;
          -  Patients treated with immune checkpoint inhibitor alone or in combination with&#xD;
             chemotherapy in 1st or 2nd line&#xD;
&#xD;
          -  Patient with locally advanced or metastatic Non-Small-Cell Lung Cancer, or bladder&#xD;
             cancer or Ear Nose Throat cancer&#xD;
&#xD;
          -  Maximum delay of 2 months between ICI and chemotherapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Symptomatic brain metastases&#xD;
&#xD;
          -  Corticotherapy &gt; 10 mg/day&#xD;
&#xD;
          -  Active auto-immune disease&#xD;
&#xD;
          -  Oncogenic addiction&#xD;
&#xD;
          -  Data processing objection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Medical oncology department, University Hospital, Tours</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pneumology department, University Hospital, Tours</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <last_update_submitted>April 5, 2023</last_update_submitted>
  <last_update_submitted_qc>April 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Immunity checkpoint inhibitor</keyword>
  <keyword>Rescue chemotherapy</keyword>
  <keyword>Non Small Cell Lung Cancer</keyword>
  <keyword>Bladder Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Urinary Bladder Neoplasms</mesh_term>
  </condition_browse>
  <!-- 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/NCT04487457
org study id: RIPH3-RNI20 / CINECI
secondary id: 2020-A01478-31
nct id: NCT04487457
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Non-small cell lung cancer (NSCLC) is the most common histological form, accounting for 85%
      of all bronchopulmonary cancers (PBC). The advent of Immunity Checkpoint Inhibitors (ICIs)
      targeting Programmed cell Death-1 (PD-1) is changing current treatment algorithms.

      Preliminary results from work carried out in the Medical Oncology Department of the
      University Hospital of Tours suggest that immunotherapy targeting ICI, when administered
      beforehand, increases the effect of catch-up chemotherapy. In NSCLC, the progression-free
      survival (PFS) of 3rd line chemotherapy after anti-PD-1 immunotherapy was better than the PFS
      of 3rd line chemotherapy performed at the end of conventional chemotherapy. Moreover, the
      combination of chemotherapy and immunotherapy gives paradoxically better results than
      immunotherapy alone.

      Immunotherapy restores the anti-tumor T immunity inhibited by the cancer cell. While the mode
      of action of ICIs is well known, the mechanisms of resistance to them are poorly understood.
      Several pathways are evoked, in particular the modulation of cellular interactions within the
      tumour microenvironment (TME), the molecular expression profile of cancer cells, or the
      immunological status of the patient.

      Regulatory T lymphocytes (Treg) participate in the maintenance of immune system homeostasis
      by ensuring tolerance to self antigens. Within TME, Treg inhibit anti-tumor T cell activity
      and potentiate tumor proliferation. The latter, by specifically recognizing tumor antigens,
      block the activity of effector T lymphocytes directed against tumor cells. Thus, an increase
      in circulating Treg concentrations and in TME is a poor prognostic factor, especially in
      NSCLC.

      Gemcitabine chemotherapy is commonly used in the management of NSCLC. Recent data show that
      gemcitabine decreases Treg activity and regulates levels of anti-inflammatory TME cytokines
      such as IL10, TGF-β and interferon-Ɣ.

      The hypothesis of this study is that the decrease in Treg blood concentration by catch-up
      chemotherapy restores sensitivity to immunotherapy.
Non-small cell lung cancer (NSCLC) is the most common histological form, accounting for 85%
      of all bronchopulmonary cancers (PBC). The advent of Immunity Checkpoint Inhibitors (ICIs)
      targeting Programmed cell Death-1 (PD-1) is changing current treatment algorithms.

      Preliminary results from work carried out in the Medical Oncology Department of the
      University Hospital of Tours suggest that immunotherapy targeting ICI, when administered
      beforehand, increases the effect of catch-up chemotherapy. In NSCLC, the the progression-free
      survival (PFS) of 3rd line chemotherapy after anti-PD-1 immunotherapy was better than the PFS
      of 3rd line chemotherapy performed at the end of conventional chemotherapy. Moreover, the
      combination of chemotherapy and immunotherapy gives paradoxically better results than
      immunotherapy alone.

      Immunotherapy restores the anti-tumor T immunity inhibited by the cancer cell. While the mode
      of action of ICIs is well known, the mechanisms of resistance to them are poorly understood.
      Several pathways are evoked, in particular the modulation of cellular interactions within the
      tumour microenvironment (TME), the molecular expression profile of cancer cells, or the
      immunological status of the patient.

      Regulatory T lymphocytes (Treg) participate in the maintenance of immune system homeostasis
      by ensuring tolerance to self antigens. Within TME, Treg inhibit anti-tumor T cell activity
      and potentiate tumor proliferation. The latter, by specifically recognizing tumor antigens,
      block the activity of effector T lymphocytes directed against tumor cells. Thus, an increase
      in circulating Treg concentrations and in TME is a poor prognostic factor, especially in
      NSCLC.

      Gemcitabine chemotherapy is commonly used in the management of NSCLC. Recent data show that
      gemcitabine decreases Treg activity and regulates levels of anti-inflammatory TME cytokines
      such as IL10, TGF-β and interferon-Ɣ.

      The hypothesis of this study is that the decrease in Treg blood concentration by catch-up
      chemotherapy restores sensitivity to immunotherapy.
observational model: Cohort
time perspective: Prospective
measure: Change from baseline blood concentration of regulatory T-lymphocytes (Treg) at 6 months
time frame: Baseline, 3 months and 6 months
description: Blood concentrations will be measured at specific times
measure: Change from baseline blood concentration of lymphocyte populations T, B, NK, CD4+ and CD8+ (effector T-lymphocytes (Teff) included) at 6 months
time frame: Baseline, 3 months and 6 months
description: Blood concentrations will be measured at specific times
measure: Change from baseline blood concentration of anti-inflammatory cytokines at 6 months
time frame: Baseline, 3 months and 6 months
description: Blood concentrations will be measured at specific times
measure: Assess correlation between blood concentration of Treg, blood concentration of Teff and blood concentration of anti-inflammatory cytokines
time frame: Baseline, 3 months and 6 months
measure: Determination of PDL1 status
time frame: Baseline
arm group label: Cancer
description: Patients receiving chemotherapy alone after immunotherapy for NSCLC or bladder cancer or ENT cancer
intervention type: Other
intervention name: Blood samples
description: Blood samples
arm group label: Cancer
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Urinary Bladder Neoplasms