<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/NCT03837054</url>
  </required_header>
  <id_info>
    <org_study_id>2018-63</org_study_id>
    <nct_id>NCT03837054</nct_id>
  </id_info>
  <brief_title>Does Chemotherapy Train the Mutation of the Pig-A Gene? (PIGA)</brief_title>
  <official_title>Does Chemotherapy Train the Mutation of the Pig-A Gene?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique Hopitaux De Marseille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique Hopitaux De Marseille</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The PIG-A gene (in humans)/Pig-a (in rodents) may be a useful reporter of acquired gene&#xD;
      mutation. A simple and reproductive test based on flow cytometry allows detection of Pig-a&#xD;
      mutants in a few minutes with low blood volumes. Many studies in rodents showed that&#xD;
      detecting Pig-a mutations is useful for identifying genotoxic exposure, but studies are&#xD;
      needed in humans to validate this biological marker. The investigators propose to carry out a&#xD;
      study to assess the prevalence of PIG-A mutated reticulocytes among 30 patients exposed to&#xD;
      genotoxic chemotherapy for breast cancer treatment. The investigators will prospectively&#xD;
      collect, for each patient, 4 blood samples of 10mL during chemotherapy: the first one (T0)&#xD;
      before chemotherapy (before genotoxic exposure), T1 during treatment (after the third cure),&#xD;
      T2 (just at the end of chemotherapy) and T3 (five weeks after the end of chemotherapy). PIG-A&#xD;
      mutated cells frequency distributions will be compared between T0, T1, T2 and T3. At the same&#xD;
      time, the investigators will document the impact of such a genotoxic exposure using the&#xD;
      micronuclei test on in vitro binucleate lymphocytes. The micronuclei test reveals structural&#xD;
      or numerical chromosome aberrations caused by aneugenic or clastogenic exposure. This test&#xD;
      will be done on T0 and T3 blood samples of each patient.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 10, 2019</start_date>
  <completion_date type="Anticipated">January 10, 2021</completion_date>
  <primary_completion_date type="Anticipated">January 10, 2021</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>analysis of the frequency of reticulocytes PIG-A mutated</measure>
    <time_frame>24 months</time_frame>
    <description>The analyzes will be applied at T0 to determine the intra-assay reproducibility. The frequency distributions of mutated cells will be compared:&#xD;
Between the two groups of patients at T0 then,&#xD;
Within each group between T0 (before exposure), T1 (in process), T2 (end of treatment) and T3 (in therapeutic monitoring post) using non-parametric tests on paired and unpaired.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>analysis of the binucleated cell micronuclei frequency in culture</measure>
    <time_frame>24 months</time_frame>
    <description>Determining the frequency of micronucleated binucleate cells in culture will be performed on the samples at T0 and T3 each patient of both groups. The frequency distribution of micronucleated cells will be compared within each group between T0 and T3 using non-parametric tests on paired series. A difference shall be considered significant if p &lt;0.05.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Breast Cancer Female</condition>
  <arm_group>
    <arm_group_label>Breast cancer patients with external polychemotherapy</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Blood collection and Micronuclei assay on binucleate lymphocytes in culture</intervention_name>
    <description>The activity of the oncology Department of the North Hospital ensures the quick and easy recruitment of 30 patients over the 10-month inclusion period. The collection of samples will be done in a forward-looking manner during chemotherapy and at different times. The patients will have 4 blood samples of 10 mL carried out during their chemotherapy with a sampling at T0 (before the initiation of chemotherapy), then to T1 (after the first 3 cures), to T2 (after the 6th cure) and to T3 is 5 weeks after the end of the chemo And before the onset of radiation therapy. The samples will be carried out within the Medical Oncology Department of the hospital Nord of Marseille.&#xD;
We will also perform micronuclei testing on Binucleate lymphocytes in culture. The lymphocyte Micronuclei test reveals structure and number chromosomal damage and allows to reveal clastogenic or eugènes exposures.</description>
    <arm_group_label>Breast cancer patients with external polychemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Major patients&#xD;
&#xD;
          -  Patients with breast cancer&#xD;
&#xD;
          -  Who have benefited from breast surgical treatment and have a poly-chemotherapy&#xD;
             adjuvanted by FEC100 and Docetaxel.&#xD;
&#xD;
          -  Patients should be able to read and understand French.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Minor Patients&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Patients who do not speak French and/or are unable to read and understand French.&#xD;
&#xD;
          -  Patients who have had a history of radiotherapy, including those who have received a&#xD;
             per-operative radiation therapy as part of the initial management of breast cancer&#xD;
&#xD;
          -  Patients who have had a history of chemotherapy outside of the chemotherapy possibly&#xD;
             received in the treatment of current breast cancer.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean Olivier Arnaud, Director</last_name>
    <role>Study Director</role>
    <affiliation>Assistance Publique Hôpitaux de Marseille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>CARCOPINO Xavier, PU-PH</last_name>
    <phone>04 91 96 46 72</phone>
    <email>xavier.carcopino-usoli@mail.ap-hm.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>: Service de Gynécologie Obstétrique Hôpital Nord</name>
      <address>
        <city>Marseille</city>
        <state>Marseille Cedex 20</state>
        <zip>13915</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xavier Carcopino, PU-PH</last_name>
      <phone>04 91 96 46 72</phone>
      <email>xavier.carcopino-usoli@mail.ap-hm.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>February 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>February 8, 2019</last_update_submitted>
  <last_update_submitted_qc>February 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT03837054
org study id: 2018-63
nct id: NCT03837054
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The PIG-A gene (in humans)/Pig-a (in rodents) may be a useful reporter of acquired gene
      mutation. A simple and reproductive test based on flow cytometry allows detection of Pig-a
      mutants in a few minutes with low blood volumes. Many studies in rodents showed that
      detecting Pig-a mutations is useful for identifying genotoxic exposure, but studies are
      needed in humans to validate this biological marker. The investigators propose to carry out a
      study to assess the prevalence of PIG-A mutated reticulocytes among 30 patients exposed to
      genotoxic chemotherapy for breast cancer treatment. The investigators will prospectively
      collect, for each patient, 4 blood samples of 10mL during chemotherapy: the first one (T0)
      before chemotherapy (before genotoxic exposure), T1 during treatment (after the third cure),
      T2 (just at the end of chemotherapy) and T3 (five weeks after the end of chemotherapy). PIG-A
      mutated cells frequency distributions will be compared between T0, T1, T2 and T3. At the same
      time, the investigators will document the impact of such a genotoxic exposure using the
      micronuclei test on in vitro binucleate lymphocytes. The micronuclei test reveals structural
      or numerical chromosome aberrations caused by aneugenic or clastogenic exposure. This test
      will be done on T0 and T3 blood samples of each patient.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: analysis of the frequency of reticulocytes PIG-A mutated
time frame: 24 months
description: The analyzes will be applied at T0 to determine the intra-assay reproducibility. The frequency distributions of mutated cells will be compared:
Between the two groups of patients at T0 then,
Within each group between T0 (before exposure), T1 (in process), T2 (end of treatment) and T3 (in therapeutic monitoring post) using non-parametric tests on paired and unpaired.
measure: analysis of the binucleated cell micronuclei frequency in culture
time frame: 24 months
description: Determining the frequency of micronucleated binucleate cells in culture will be performed on the samples at T0 and T3 each patient of both groups. The frequency distribution of micronucleated cells will be compared within each group between T0 and T3 using non-parametric tests on paired series. A difference shall be considered significant if p <0.05.
arm group label: Breast cancer patients with external polychemotherapy
arm group type: Other
intervention type: Biological
intervention name: Blood collection and Micronuclei assay on binucleate lymphocytes in culture
description: The activity of the oncology Department of the North Hospital ensures the quick and easy recruitment of 30 patients over the 10-month inclusion period. The collection of samples will be done in a forward-looking manner during chemotherapy and at different times. The patients will have 4 blood samples of 10 mL carried out during their chemotherapy with a sampling at T0 (before the initiation of chemotherapy), then to T1 (after the first 3 cures), to T2 (after the 6th cure) and to T3 is 5 weeks after the end of the chemo And before the onset of radiation therapy. The samples will be carried out within the Medical Oncology Department of the hospital Nord of Marseille.
We will also perform micronuclei testing on Binucleate lymphocytes in culture. The lymphocyte Micronuclei test reveals structure and number chromosomal damage and allows to reveal clastogenic or eugènes exposures.
arm group label: Breast cancer patients with external polychemotherapy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean Olivier Arnaud, Director
role: Study Director
affiliation: Assistance Publique Hôpitaux de Marseille
last name: CARCOPINO Xavier, PU-PH
phone: 04 91 96 46 72
email: xavier.carcopino-usoli@mail.ap-hm.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor