<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/NCT03000764</url>
  </required_header>
  <id_info>
    <org_study_id>2016-A00592-49</org_study_id>
    <nct_id>NCT03000764</nct_id>
  </id_info>
  <brief_title>RNA and Heat Shock Protein Biomarkers in Radiation-induced Fibrosis in Breast Cancer</brief_title>
  <acronym>SPLICI-Rad</acronym>
  <official_title>Study of RNA and Heat Shock Protein (HSP) Derived Biomarkers in Radiation-induced Fibrosis in Patients Treated for Breast Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut de Cancérologie de Lorraine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut de Cancérologie de Lorraine</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>
      The purpose of this study is to seeking a molecular signature of pathological radiation&#xD;
      induced fibrosis based on the response of skin fibroblasts after irradiation, comparing two&#xD;
      groups of patients distinguished by their individual radiosensitivity. The signature will&#xD;
      integrate recent insights in terms of alternative splicing of mRNAs and level of expression&#xD;
      of non-coding RNAs, particularly long non-coding RNAs, snRNAs, snoRNAs and microRNAs. In each&#xD;
      group each expression patterns of candidate HSP proteins potentially predictive of&#xD;
      pathological radiation induced fibrosis (HSP27, HSP70, αβ crystalline) in the serum and on&#xD;
      cell culture will be characterized.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 10, 2017</start_date>
  <completion_date type="Actual">April 25, 2018</completion_date>
  <primary_completion_date type="Actual">April 18, 2018</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Global mRNA alternative splicing and expression of non-coding RNAs profiles in healthy dermal fibroblasts</measure>
    <time_frame>6 months</time_frame>
    <description>frequency of inclusion of individual exons within the set of mRNA isoforms (overall splicing profile) and variation in expression of non-coding RNAs</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on cultured fibroblasts</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on serum</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Individual radiosensitivity on healthy dermal fibroblasts</measure>
    <time_frame>6 months</time_frame>
    <description>The micronuclei will be counted 24 hours after ex vivo irradiation with an indirect immunofluorescence assay (53BP1 + pATM antibodies)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of the overall mRNA splicing and non-coding RNA expression profiles between non irradiated and irradiated dermal fibroblasts in the same individual</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in cellular distribution of the main non-coding RNAs whose expression varies significantly within the pre-identified signature between the 2 groups of patients</measure>
    <time_frame>6 months</time_frame>
    <description>The cellular distribution is defined as the compartment (nucleoplasm, nucleolus, intra-nuclear corpuscles, cytosol, RE, mitochondria ...) marked by the fluorescent probe labeled to the non-coding RNAs of interest (RNA-FISH)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>seric HSP proteins potentially predictive of pathological induced fibrosis</measure>
    <time_frame>6 months</time_frame>
    <description>HSP27, HSP70 and αB crystalline measured in serum with ELISA assay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cellular distribution of specific HSP on fibroblast culture in each group of patients</measure>
    <time_frame>6 months</time_frame>
    <description>immunolabeling of HSPs and spatial mapping and sub-nuclear distributions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Potential interactions between DNA damage response proteins and candidate HSP</measure>
    <time_frame>6 months</time_frame>
    <description>Collocation of HSPs with pATM and 53-BP1 (confocal microscopy / FLIM)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Breast Carcinoma</condition>
  <condition>Fibrosis</condition>
  <arm_group>
    <arm_group_label>Biomarkers</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>skin biopsies</intervention_name>
    <description>Biopsies (12 G) will be performed :&#xD;
in non-irradiated breast skin&#xD;
in irradiated breast skin</description>
    <arm_group_label>Biomarkers</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>blood samples</intervention_name>
    <description>blood samples are collected:&#xD;
10 ml in EDTA tube&#xD;
2,5 ml in PAXgene Blood RNA tube&#xD;
4 ml in EDTA tube</description>
    <arm_group_label>Biomarkers</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  women&#xD;
&#xD;
          -  age ≥ 18 and &lt;70 years old&#xD;
&#xD;
          -  non metastatic disease&#xD;
&#xD;
          -  ECOG performance status 0 or 1&#xD;
&#xD;
          -  chest size ≤ 110 cm et bra size &lt;D&#xD;
&#xD;
          -  absence of reconstructive breast surgery&#xD;
&#xD;
          -  patient able to undergo blood samples (haematological conditions allowing blood&#xD;
             sample)&#xD;
&#xD;
          -  non-evolving carcinological disease&#xD;
&#xD;
          -  absence of systemic inflammatory disease (other than scleroderma) or diabetes&#xD;
&#xD;
          -  no inflammatory ou infectious flare on biopsy site at the time of inclusion&#xD;
&#xD;
          -  invasive or in situ breast carcinoma&#xD;
&#xD;
          -  ability to provide an informed written consent form&#xD;
&#xD;
          -  affiliation to a social security system&#xD;
&#xD;
        Then stratification into two groups :&#xD;
&#xD;
        group 1 : radio-sensitive patients&#xD;
&#xD;
          -  Post-operative radiotherapy completed at least 6 months ago AND&#xD;
&#xD;
          -  radiation induced dermal and/or soft tissue toxicity (dermatitis, fibrosis, atrophy)&#xD;
             rated &gt; 2 (CTCAE v4.0 scale)&#xD;
&#xD;
        group 2 : radio-tolerant (control) patients&#xD;
&#xD;
          -  Post-operative radiotherapy completed more than 4 years ago AND&#xD;
&#xD;
          -  radiation induced dermal and/or soft tissue toxicity (dermatitis, fibrosis, atrophy)&#xD;
             rated ≤1 (CTCAE v4.0 scale) .&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age &lt;18 or &gt; 70 years old&#xD;
&#xD;
          -  evolutive cancer / metastatic disease&#xD;
&#xD;
          -  chest size &gt; 110 cm et bra size ≥ D&#xD;
&#xD;
          -  previous reconstructive breast surgery&#xD;
&#xD;
          -  ECOG performance status &gt; 1&#xD;
&#xD;
          -  systemic inflammatory disease or diabetes&#xD;
&#xD;
          -  inflammatory ou infectious flare on biopsy site at the time of inclusion, very&#xD;
             significant ulceration in the treated breast&#xD;
&#xD;
          -  anemic patients&#xD;
&#xD;
          -  use of oral anticoagulants&#xD;
&#xD;
          -  pregnant or likely to be in 6 months&#xD;
&#xD;
          -  patients deprived of liberty or under supervision&#xD;
&#xD;
          -  non-affiliation to a social security system&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>VOGIN GUILLAUME, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut de Cancérologie de Lorraine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>BEHM-ANSMANT Isabelle, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UMR 7365 CNRS-Université de Lorraine, IMoPA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut de Cancérologie de Lorraine</name>
      <address>
        <city>Vandœuvre-lès-Nancy</city>
        <zip>54519</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 22, 2016</study_first_posted>
  <last_update_submitted>August 7, 2018</last_update_submitted>
  <last_update_submitted_qc>August 7, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Skin biopsy</keyword>
  <keyword>Radiotherapy</keyword>
  <keyword>RNA biomarker</keyword>
  <keyword>HSP biomarker</keyword>
  <keyword>Exon junction array</keyword>
  <keyword>Gene expression</keyword>
  <keyword>Radiosensitivity prediction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
    <mesh_term>Radiation Fibrosis Syndrome</mesh_term>
  </condition_browse>
  <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/NCT03000764
org study id: 2016-A00592-49
nct id: NCT03000764
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to seeking a molecular signature of pathological radiation
      induced fibrosis based on the response of skin fibroblasts after irradiation, comparing two
      groups of patients distinguished by their individual radiosensitivity. The signature will
      integrate recent insights in terms of alternative splicing of mRNAs and level of expression
      of non-coding RNAs, particularly long non-coding RNAs, snRNAs, snoRNAs and microRNAs. In each
      group each expression patterns of candidate HSP proteins potentially predictive of
      pathological radiation induced fibrosis (HSP27, HSP70, αβ crystalline) in the serum and on
      cell culture will be characterized.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Global mRNA alternative splicing and expression of non-coding RNAs profiles in healthy dermal fibroblasts
time frame: 6 months
description: frequency of inclusion of individual exons within the set of mRNA isoforms (overall splicing profile) and variation in expression of non-coding RNAs
measure: Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on cultured fibroblasts
time frame: 6 months
measure: Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on serum
time frame: 6 months
measure: Individual radiosensitivity on healthy dermal fibroblasts
time frame: 6 months
description: The micronuclei will be counted 24 hours after ex vivo irradiation with an indirect immunofluorescence assay (53BP1 + pATM antibodies)
measure: Comparison of the overall mRNA splicing and non-coding RNA expression profiles between non irradiated and irradiated dermal fibroblasts in the same individual
time frame: 6 months
measure: Changes in cellular distribution of the main non-coding RNAs whose expression varies significantly within the pre-identified signature between the 2 groups of patients
time frame: 6 months
description: The cellular distribution is defined as the compartment (nucleoplasm, nucleolus, intra-nuclear corpuscles, cytosol, RE, mitochondria ...) marked by the fluorescent probe labeled to the non-coding RNAs of interest (RNA-FISH)
measure: seric HSP proteins potentially predictive of pathological induced fibrosis
time frame: 6 months
description: HSP27, HSP70 and αB crystalline measured in serum with ELISA assay
measure: Cellular distribution of specific HSP on fibroblast culture in each group of patients
time frame: 6 months
description: immunolabeling of HSPs and spatial mapping and sub-nuclear distributions
measure: Potential interactions between DNA damage response proteins and candidate HSP
time frame: 6 months
description: Collocation of HSPs with pATM and 53-BP1 (confocal microscopy / FLIM)
arm group label: Biomarkers
arm group type: Experimental
intervention type: Other
intervention name: skin biopsies
description: Biopsies (12 G) will be performed :
in non-irradiated breast skin
in irradiated breast skin
arm group label: Biomarkers
intervention type: Other
intervention name: blood samples
description: blood samples are collected:
10 ml in EDTA tube
2,5 ml in PAXgene Blood RNA tube
4 ml in EDTA tube
arm group label: Biomarkers
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: VOGIN GUILLAUME, MD, PhD
role: Principal Investigator
affiliation: Institut de Cancérologie de Lorraine
last name: BEHM-ANSMANT Isabelle, PhD
role: Principal Investigator
affiliation: UMR 7365 CNRS-Université de Lorraine, IMoPA
facility: 
country: France
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Fibrosis
mesh term: Radiation Fibrosis Syndrome
sharing ipd: No