<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/NCT03303885</url>
  </required_header>
  <id_info>
    <org_study_id>16-PRTK</org_study_id>
    <nct_id>NCT03303885</nct_id>
  </id_info>
  <brief_title>The FGF/FGFR Signalling Pathway:</brief_title>
  <acronym>FILIPO</acronym>
  <official_title>The FGF/FGFR Signalling Pathway: a Novel Therapeutic Target in Liposarcomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Nice</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Nice</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Liposarcomas are the most common type of soft tissue sarcomas (STS). Among liposarcomas,&#xD;
      well-differentiated liposarcoma (WDLPS)/dedifferentiated liposarcoma (DDLPS) are the most&#xD;
      frequent types. WDLPS are composed mostly of mature fat whereas DDLPS contain both a WDLPS&#xD;
      component and a non-lipomatous sarcoma component mostly of high grade. More than 50% of DDLPS&#xD;
      will relapse locally. A significant proportion of patients will remain with a non-resectable&#xD;
      disease that will metastasize in 20% of cases. Standard chemotherapy is poorly efficient and&#xD;
      alternative options are so far limited. Identification of new therapeutic targets is urgent&#xD;
      and mandatory. the recent preliminary results as well as data from the literature led us to&#xD;
      hypothesize that the FGF (Fibroblast Growth factor)/FGFR pathway is involved in&#xD;
      liposarcomagenesis and might therefore be a novel relevant therapeutic target in WDLPS/DDLPS.&#xD;
&#xD;
      Description of the project The project associates 4 teams with a longstanding collaboration :&#xD;
      3 teams fom Nice (Nice University Hospital/IRCAN, Nice University Hospital, Comprehensive&#xD;
      Cancer Center Centre Antoine Lacassagne and one team from Bordeaux (Comprehensive Cancer&#xD;
      Center Institut Bergonié). These 4 teams are experts in the clinics, pathology and molecular&#xD;
      genetics of sarcomas as well as in biostatistics.&#xD;
&#xD;
        1. Expression studies on the role of the syndecan-1 (SDC1)/FGFR pathway in WDLPS/DDLPS&#xD;
           tumorigenesis&#xD;
&#xD;
           The recent studies provide original results that may have a direct application in&#xD;
           treatments of liposarcomas. They suggest that SDC1 -an effector of the FGF/FGFR pathway-&#xD;
           might be involved in DDLPS tumorigenesis. Staff will analyse:&#xD;
&#xD;
             -  The pattern of expression and localisation of syndecans, FGFs and FGFRs in&#xD;
                WDLPS/DDLPS both in a large collection of 249 primary tumors and in our in-house&#xD;
                panel of high quality and validated human WDLPS/DDLPS cell lines.&#xD;
&#xD;
             -  The prognostic value of SDC1, FGF2 and FGF18 expression by correlation to the&#xD;
                patient clinical outcomes&#xD;
&#xD;
        2. Fonctional studies of the role of the SDC1/FGFR pathway in WDLPS/DDLPS tumorigenesis. We&#xD;
           will analyse:&#xD;
&#xD;
             -  The effects of modulating SDC1, FGFR expression in WDLPS and DDLPS cells on cell&#xD;
                proliferation, cell cycle, apoptosis and on their capacity to differentiate in&#xD;
                adipocytes.&#xD;
&#xD;
             -  The sensitivity of WDLPS and DDLPS cells to the FGFR inhibitor JNJ-427556493 as a&#xD;
                single agent or in combination with other antagonists.&#xD;
&#xD;
             -  The mechanisms of sensitivity and resistance to JNJ-427556493 by phosphoproteomic&#xD;
                analysis of WDLPS and DDLPS cells before and after JNJ-427556493 treatment.&#xD;
&#xD;
             -  The involvement of SDC1 in the dedifferentiation process of liposarcoma. Expected&#xD;
                results staff expect to demonstrate the relevance of the SDC1/FGFR pathway in&#xD;
                liposarcomas. We also expect to link drug activity to genomics and proteomics data.&#xD;
                This will allow the characterization of the activity of FGFR inhibitors and the&#xD;
                identification of powerful preclinical biomarkers of drug activity and mechanisms&#xD;
                of resistance in DDLPS. The availability of xenograft models will allow us to&#xD;
                validate our in vitro findings in the in vivo setting with the ultimate goal to&#xD;
                improve patient management.&#xD;
&#xD;
      The availability of an early clinical trial unit in Institut Bergonié, managed by A.&#xD;
      Italiano, will give the immediate opportunity to transfer our data to the management of&#xD;
      metastatic liposarcoma patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Actual">March 29, 2019</completion_date>
  <primary_completion_date type="Actual">March 29, 2019</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <target_duration>24 Months</target_duration>
  <primary_outcome>
    <measure>difference in terms of overall survival: between FGF18 - versus FGF18+</measure>
    <time_frame>24 months</time_frame>
    <description>overall survival, recurrence</description>
  </primary_outcome>
  <enrollment type="Actual">421</enrollment>
  <condition>Liposarcoma</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Liposarcoma biopsy&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        biopsy of liposarcoma patient&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A biopsy and\or an exérèse with diagnostic or curative aim will have been practised&#xD;
             within the framework of a well differentiated liposarcome or dédifférencié with&#xD;
             development of the gene MDM2&#xD;
&#xD;
          -  A taking of the tumor is available (frozen fragment and\or block fixed in paraffin&#xD;
             wax) - not opposition of the patient will have been looked for&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Liposarcome not differentiated&#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>Nice Hospital</name>
      <address>
        <city>Nice</city>
        <zip>06000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>October 3, 2017</study_first_submitted>
  <study_first_submitted_qc>October 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <last_update_submitted>October 15, 2020</last_update_submitted>
  <last_update_submitted_qc>October 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 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>Liposarcoma</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/NCT03303885
org study id: 16-PRTK
nct id: NCT03303885
lead sponsor: 
has dmc: No
is fda regulated device: No
Liposarcomas are the most common type of soft tissue sarcomas (STS). Among liposarcomas,
      well-differentiated liposarcoma (WDLPS)/dedifferentiated liposarcoma (DDLPS) are the most
      frequent types. WDLPS are composed mostly of mature fat whereas DDLPS contain both a WDLPS
      component and a non-lipomatous sarcoma component mostly of high grade. More than 50% of DDLPS
      will relapse locally. A significant proportion of patients will remain with a non-resectable
      disease that will metastasize in 20% of cases. Standard chemotherapy is poorly efficient and
      alternative options are so far limited. Identification of new therapeutic targets is urgent
      and mandatory. the recent preliminary results as well as data from the literature led us to
      hypothesize that the FGF (Fibroblast Growth factor)/FGFR pathway is involved in
      liposarcomagenesis and might therefore be a novel relevant therapeutic target in WDLPS/DDLPS.

      Description of the project The project associates 4 teams with a longstanding collaboration :
      3 teams fom Nice (Nice University Hospital/IRCAN, Nice University Hospital, Comprehensive
      Cancer Center Centre Antoine Lacassagne and one team from Bordeaux (Comprehensive Cancer
      Center Institut Bergonié). These 4 teams are experts in the clinics, pathology and molecular
      genetics of sarcomas as well as in biostatistics.

        1. Expression studies on the role of the syndecan-1 (SDC1)/FGFR pathway in WDLPS/DDLPS
           tumorigenesis

           The recent studies provide original results that may have a direct application in
           treatments of liposarcomas. They suggest that SDC1 -an effector of the FGF/FGFR pathway-
           might be involved in DDLPS tumorigenesis. Staff will analyse:

             -  The pattern of expression and localisation of syndecans, FGFs and FGFRs in
                WDLPS/DDLPS both in a large collection of 249 primary tumors and in our in-house
                panel of high quality and validated human WDLPS/DDLPS cell lines.

             -  The prognostic value of SDC1, FGF2 and FGF18 expression by correlation to the
                patient clinical outcomes

        2. Fonctional studies of the role of the SDC1/FGFR pathway in WDLPS/DDLPS tumorigenesis. We
           will analyse:

             -  The effects of modulating SDC1, FGFR expression in WDLPS and DDLPS cells on cell
                proliferation, cell cycle, apoptosis and on their capacity to differentiate in
                adipocytes.

             -  The sensitivity of WDLPS and DDLPS cells to the FGFR inhibitor JNJ-427556493 as a
                single agent or in combination with other antagonists.

             -  The mechanisms of sensitivity and resistance to JNJ-427556493 by phosphoproteomic
                analysis of WDLPS and DDLPS cells before and after JNJ-427556493 treatment.

             -  The involvement of SDC1 in the dedifferentiation process of liposarcoma. Expected
                results staff expect to demonstrate the relevance of the SDC1/FGFR pathway in
                liposarcomas. We also expect to link drug activity to genomics and proteomics data.
                This will allow the characterization of the activity of FGFR inhibitors and the
                identification of powerful preclinical biomarkers of drug activity and mechanisms
                of resistance in DDLPS. The availability of xenograft models will allow us to
                validate our in vitro findings in the in vivo setting with the ultimate goal to
                improve patient management.

      The availability of an early clinical trial unit in Institut Bergonié, managed by A.
      Italiano, will give the immediate opportunity to transfer our data to the management of
      metastatic liposarcoma patients.
observational model: Other
time perspective: Cross-Sectional
measure: difference in terms of overall survival: between FGF18 - versus FGF18+
time frame: 24 months
description: overall survival, recurrence
Liposarcoma biopsy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: France
responsible party type: Sponsor
mesh term: Liposarcoma
sharing ipd: Undecided