<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/NCT04477876</url>
  </required_header>
  <id_info>
    <org_study_id>APHP190953</org_study_id>
    <nct_id>NCT04477876</nct_id>
  </id_info>
  <brief_title>Study of CD160, an Activating NK Cell Receptor, in Melanoma: a Potential Therapeutic Target?</brief_title>
  <acronym>NKCD160MEL</acronym>
  <official_title>Study of CD160, an Activating NK Cell Receptor, in Melanoma: a Potential Therapeutic Target?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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>
      Although immunotherapy revolutionized melanoma outcomes over the last 10 years, only 40-50%&#xD;
      of patients respond to treatments and 25% develop acquired resistances. Natural Killer (NK)&#xD;
      cells naturally recognize and kill tumor cells. However, the immunosuppressive&#xD;
      micro-environment generated by the tumor decreases NK cells' killing activity. CD160 is a NK&#xD;
      cell receptor identified and characterized in our laboratory. Engagement of the GPI isoform&#xD;
      (CD160-GPI) initiates NK cell cytotoxic response. Upon NK cell activation, a transmembrane&#xD;
      isoform (CD160-TM) is neo-synthesized which promotes the amplification of activated NK cell&#xD;
      cytotoxicity.&#xD;
&#xD;
      The aim of this study is to assess the phenotypic profile of advanced stages melanoma&#xD;
      patients' NK cells (mainly CD160-TM expression or its induction) and therefore the&#xD;
      therapeutic potential of the use of an anti-CD160-TM agonist antibody to boost the&#xD;
      NK-dependent mechanism leading to tumor depletion.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">September 1, 2020</start_date>
  <completion_date type="Anticipated">December 15, 2027</completion_date>
  <primary_completion_date type="Anticipated">December 15, 2027</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>Percentage of effector cells activation and degranulation (CD69 and CD107a staining )</measure>
    <time_frame>at inclusion</time_frame>
    <description>Difference between cells incubated with the anti CD160-TM antibody and with isotipic control ab ( flow cytometry)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>at 1 year post inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>at 2 years post inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>at 3 years post inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>at 4 years post inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>at 5 years post inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>at 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>at 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>at 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>at 4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>at 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>at one year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>at 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>at 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>at 4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>at 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phenotypic characteristics of NK cells</measure>
    <time_frame>at inclusion</time_frame>
    <description>Assessment by flow cytometry of the expression levels of activating or inhibitory receptors (e.g. CD160-GPI, NKp46), phenotypic markers (e.g CD16, CD3), as well as activation (CD69) and degranulation (CD107a) markers by the NK cell population (defined as CD3- CD56+ cell). Results will be expressed as the % of positive cells for each marker among the NK cell population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cytokine profile</measure>
    <time_frame>at inclusion</time_frame>
    <description>Assessment by flow cytometry using a cytokine beads array (BD Biosciences) of the Th1/Th2/Th17 cytokine content. The presence of the following cytokine will be assessed: IL17-A, IFN-g, TNF, IL10, IL-6, IL-4 and IL-2. The mean fluorescence intensities will be recorded and quantifications will be done, using an individual standard curve, for each cytokine. Results will be expressed in pg/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Détection and quantification of sCD160 in patients' serum</measure>
    <time_frame>at inclusion</time_frame>
  </secondary_outcome>
  <enrollment type="Anticipated">55</enrollment>
  <condition>Melanoma</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Inoperable stage III/ stage IV melanoma patients&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria :&#xD;
&#xD;
          -  Patients aged18-years old or over&#xD;
&#xD;
          -  ECOG score between 0-2&#xD;
&#xD;
          -  Inoperable stage III or stage IV melanoma&#xD;
&#xD;
          -  Naïve of treatment or in progression after one or several treatment lines&#xD;
&#xD;
          -  Give their written consent for the present study and be included in MelBase cohort.&#xD;
&#xD;
          -  health insurance coverage.&#xD;
&#xD;
        Supplementary inclusion criteria for part II :&#xD;
&#xD;
          -  skin or subcutaneous melanoma lesions&#xD;
&#xD;
          -  agree and inform consent for a cutaneous biopsy or a tumor sample if presenting lymph&#xD;
             nodes involvement if part of the usual clinical practice.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant and breastfeeding women&#xD;
&#xD;
          -  Patients with psychiatric disorders&#xD;
&#xD;
          -  Patients already included in another clinical trial&#xD;
&#xD;
          -  Having received chemotherapy or radiotherapy during the last 4 weeks,&#xD;
&#xD;
          -  Patient presenting another solid or blood cancer, chronic viral infection (e.g. HIV,&#xD;
             HBV or HCV)&#xD;
&#xD;
          -  Been treated with more than 10mg of steroids until the 4 weeks before inclusion.&#xD;
&#xD;
          -  Refusal to participate to the study&#xD;
&#xD;
          -  Patients under guardianship or curatorship&#xD;
&#xD;
          -  Patients on state medical aid&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Celeste Lebbe, Pr</last_name>
    <phone>01 42 49 99 61</phone>
    <email>celeste.lebbe@aphp.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Matthieu Resche-Rigon, Pr</last_name>
    <phone>+3342499742</phone>
    <email>matthieu.resche-rigon@univ-paris-diderot.fr</email>
  </overall_contact_backup>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>May 11, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>July 17, 2020</last_update_submitted>
  <last_update_submitted_qc>July 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04477876
org study id: APHP190953
nct id: NCT04477876
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Although immunotherapy revolutionized melanoma outcomes over the last 10 years, only 40-50%
      of patients respond to treatments and 25% develop acquired resistances. Natural Killer (NK)
      cells naturally recognize and kill tumor cells. However, the immunosuppressive
      micro-environment generated by the tumor decreases NK cells' killing activity. CD160 is a NK
      cell receptor identified and characterized in our laboratory. Engagement of the GPI isoform
      (CD160-GPI) initiates NK cell cytotoxic response. Upon NK cell activation, a transmembrane
      isoform (CD160-TM) is neo-synthesized which promotes the amplification of activated NK cell
      cytotoxicity.

      The aim of this study is to assess the phenotypic profile of advanced stages melanoma
      patients' NK cells (mainly CD160-TM expression or its induction) and therefore the
      therapeutic potential of the use of an anti-CD160-TM agonist antibody to boost the
      NK-dependent mechanism leading to tumor depletion.
observational model: Cohort
time perspective: Prospective
measure: Percentage of effector cells activation and degranulation (CD69 and CD107a staining )
time frame: at inclusion
description: Difference between cells incubated with the anti CD160-TM antibody and with isotipic control ab ( flow cytometry)
measure: Overall survival
time frame: at 1 year post inclusion
measure: Overall survival
time frame: at 2 years post inclusion
measure: Overall survival
time frame: at 3 years post inclusion
measure: Overall survival
time frame: at 4 years post inclusion
measure: Overall survival
time frame: at 5 years post inclusion
measure: Progression free survival
time frame: at 1 year
measure: Progression free survival
time frame: at 2 years
measure: Progression free survival
time frame: at 3 years
measure: Progression free survival
time frame: at 4 years
measure: Progression free survival
time frame: at 5 years
measure: Objective response rate
time frame: at one year
measure: Objective response rate
time frame: at 2 years
measure: Objective response rate
time frame: at 3 years
measure: Objective response rate
time frame: at 4 years
measure: Objective response rate
time frame: at 5 years
measure: Phenotypic characteristics of NK cells
time frame: at inclusion
description: Assessment by flow cytometry of the expression levels of activating or inhibitory receptors (e.g. CD160-GPI, NKp46), phenotypic markers (e.g CD16, CD3), as well as activation (CD69) and degranulation (CD107a) markers by the NK cell population (defined as CD3- CD56+ cell). Results will be expressed as the % of positive cells for each marker among the NK cell population
measure: cytokine profile
time frame: at inclusion
description: Assessment by flow cytometry using a cytokine beads array (BD Biosciences) of the Th1/Th2/Th17 cytokine content. The presence of the following cytokine will be assessed: IL17-A, IFN-g, TNF, IL10, IL-6, IL-4 and IL-2. The mean fluorescence intensities will be recorded and quantifications will be done, using an individual standard curve, for each cytokine. Results will be expressed in pg/ml.
measure: Détection and quantification of sCD160 in patients' serum
time frame: at inclusion
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Celeste Lebbe, Pr
phone: 01 42 49 99 61
email: celeste.lebbe@aphp.fr
last name: Matthieu Resche-Rigon, Pr
phone: +3342499742
email: matthieu.resche-rigon@univ-paris-diderot.fr
responsible party type: Sponsor
mesh term: Melanoma
sharing ipd: Undecided