<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/NCT04480814</url>
  </required_header>
  <id_info>
    <org_study_id>CBS-PIK3CA</org_study_id>
    <nct_id>NCT04480814</nct_id>
  </id_info>
  <brief_title>Validation of Molecular Diagnostic Assays to Detect Cancer Biomarkers in Blood &amp; Primary Tumor in ER+/HER2- MBC</brief_title>
  <official_title>A Clinical Performance Study to Validate the Use of Novel Molecular Diagnostic Assays for the Detection of Cancer Biomarkers in Peripheral Blood and Primary Tumor Tissue Samples of Patients With Metastatic ER+/HER2- Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pharmassist Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Athens</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Pharmassist Ltd</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>
      Conventional biopsy and surgical tumor resection are invasive procedures that capture only&#xD;
      one instance of the progression of the tumor. However, the genome of tumor is not static, but&#xD;
      it is constantly altered during treatment.&#xD;
&#xD;
      Liquid biopsy is a non-invasive approach based on the extraction of information through&#xD;
      peripheral blood analysis. It makes it possible to characterize the development of a solid&#xD;
      tumor in real time, through detailed molecular analysis of circulating genetic material in&#xD;
      peripheral blood.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Conventional biopsy and surgical tumor resection are invasive procedures that capture only&#xD;
      one instance of the progression of the tumor. However, the genome of tumor is not static, but&#xD;
      it is constantly altered during treatment.&#xD;
&#xD;
      Liquid biopsy is a non-invasive approach based on the extraction of information through&#xD;
      peripheral blood analysis. It makes it possible to characterize the development of a solid&#xD;
      tumor in real time, through detailed molecular analysis of circulating genetic material in&#xD;
      peripheral blood.&#xD;
&#xD;
      Study procedure:&#xD;
&#xD;
        1. Initial Visit (V0-Baseline): For the purposes of the study the following information&#xD;
           will be collected: the demographics, medical and social history, the characteristics of&#xD;
           the disease (stage, molecular characterization e.t.c) and the treatment regimen that is&#xD;
           followed. As part of the visit, 20 mL of peripheral blood will be drawn prior to their&#xD;
           treatment according to physician's suggestion as per common clinical practice. Blood&#xD;
           samples will be then sent to ACTC laboratory for plasma/CTC isolation, DNA and RNA&#xD;
           extraction and subsequent test for biomarkers. Primary tumor tissue samples will be also&#xD;
           collected&#xD;
&#xD;
        2. Follow-up visit (V1): Response to treatment by RECIST based on restaging CTs/MRIs will&#xD;
           be documented during this visit, which will take place 3 months after treatment&#xD;
           initiation. As part of the visit, 20 mL of peripheral blood will be drawn.&#xD;
&#xD;
      Blood samples will be then sent to laboratory for plasma/CTC isolation, DNA and RNA&#xD;
      extraction and subsequent test for biomarkers. Survival status and clinical response (CR, PR,&#xD;
      SD, PD) will be also documented.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 11, 2019</start_date>
  <completion_date type="Anticipated">June 11, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 11, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical performance of PIK3CA kit in CTCs, plasma and tumor tissue samples of metastatic breast cancer patients</measure>
    <time_frame>18 months</time_frame>
    <description>The performance of PIK3CA kit on detecting mutations in CTCs samples of metastatic breast cancer patients will be assessed via Sensitivity, Specificity, Positive and Negative Predictive Values, Positive and Negative Likelihood Ratios, Accuracy and Diagnostic Odds Ratio. The point of primary evaluation in CTCs samples will be at baseline and droplet digital PCR will be used as reference method.&#xD;
The performance of PIK3CA kit on detecting mutations in plasma-ctDNA, and tumor tissue samples of metastatic breast cancer patients will be assessed via Sensitivity, Specificity Positive and Negative Predictive Values, Positive and Negative Likelihood Ratios, Accuracy and Diagnostic Odds Ratio. The point of primary evaluation in plasma-ctDNA and tumor tissue samples will be at baseline and therascreen PIK3CA RGQ PCR Kit will be used as reference method.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>- To study the PIK3CA Mutation Status before and after treatment of metastatic breast cancer patients using PIK3CA kit.</measure>
    <time_frame>24 months</time_frame>
    <description>Presence of PIK3CA mutations at a second visit following to baseline of metastatic breast cancer patients using the PIK3CA kit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- To assess the PIK3CA Mutation Status before treatment vs treatment response of metastatic breast cancer patients using PIK3CA kit.</measure>
    <time_frame>24 months</time_frame>
    <description>Association of PIK3CA mutations presence at baseline with clinical response to treatment (CR, PR, SD, PD) of metastatic breast cancer patients using PIK3CA kit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>- To correlate patients' survival status with PIK3CA mutations at baseline</measure>
    <time_frame>24 months</time_frame>
    <description>Metastatic breast cancer patients' survival status by presence of PIK3CA mutations at baseline.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>To study CK-19 expression in CTC samples</measure>
    <time_frame>24 months</time_frame>
    <description>Detection of CK-19 expression in CTCs</description>
  </other_outcome>
  <other_outcome>
    <measure>To study methylation status of ESR1 in CTC, ctDNA and tumor tissue samples</measure>
    <time_frame>24 months</time_frame>
    <description>Methylation status of ESR1 in CTC, plasma and tumor samples</description>
  </other_outcome>
  <other_outcome>
    <measure>To study the presence of other biomarkers in tissue and liquid biopsy sample (at baseline).</measure>
    <time_frame>24 months</time_frame>
    <description>Molecular profile of cancer biomarkers between tissue and peripheral blood samples</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Metastatic Breast Cancer</arm_group_label>
    <description>The study population are subjects with a confirmed diagnosis of ER+/HER2 metastatic Breast Cancer patient before the treatment initiation.&#xD;
The selected inclusion/exclusion criteria have been set to include in the performance study appropriate population of interest, as broad as possible, but to exclude these subjects that have another current malignancy or any history of recent malignancy within 3 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <description>In case of healthy volunteers only peripheral blood samples will be collected.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>PIK3CA kit</intervention_name>
    <description>Prospective investigation of clinical samples for evaluation of IVD clinical performance</description>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <arm_group_label>Metastatic Breast Cancer</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      CTCs, plasma-ctDNA and primary tumor tissue samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        120 with metastatic breast cancer 30 healthy subjects&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female aged ≥ 18 years of age.&#xD;
&#xD;
          2. Histological confirmed ER+/HER2- metastatic Breast Cancer prior to beginning a&#xD;
             treatment&#xD;
&#xD;
          3. Life expectancy permits participation to the study.&#xD;
&#xD;
          4. Available tumor tissue sample for molecular analysis.&#xD;
&#xD;
          5. Signed informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Female younger than 18 years old.&#xD;
&#xD;
          2. History of another malignancy within 3 years or current 2nd primary malignancy.&#xD;
&#xD;
          3. Patients that have not signed the informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Aretaieio University Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <state>Attica</state>
        <zip>11528</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University General Hospital of Athens Attikon</name>
      <address>
        <city>Athens</city>
        <state>Attica</state>
        <zip>124 62</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University General Hospital of Alexandroupoli</name>
      <address>
        <city>Alexandroupolis</city>
        <zip>68100</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metropolital Hospital</name>
      <address>
        <city>Piraeus</city>
        <zip>18547</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>February 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>March 28, 2023</last_update_submitted>
  <last_update_submitted_qc>March 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Liquid biopsy</keyword>
  <keyword>CTC</keyword>
  <keyword>Plasma</keyword>
  <keyword>PIK3CA</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast 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/NCT04480814
org study id: CBS-PIK3CA
nct id: NCT04480814
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Conventional biopsy and surgical tumor resection are invasive procedures that capture only
      one instance of the progression of the tumor. However, the genome of tumor is not static, but
      it is constantly altered during treatment.

      Liquid biopsy is a non-invasive approach based on the extraction of information through
      peripheral blood analysis. It makes it possible to characterize the development of a solid
      tumor in real time, through detailed molecular analysis of circulating genetic material in
      peripheral blood.
Conventional biopsy and surgical tumor resection are invasive procedures that capture only
      one instance of the progression of the tumor. However, the genome of tumor is not static, but
      it is constantly altered during treatment.

      Liquid biopsy is a non-invasive approach based on the extraction of information through
      peripheral blood analysis. It makes it possible to characterize the development of a solid
      tumor in real time, through detailed molecular analysis of circulating genetic material in
      peripheral blood.

      Study procedure:

        1. Initial Visit (V0-Baseline): For the purposes of the study the following information
           will be collected: the demographics, medical and social history, the characteristics of
           the disease (stage, molecular characterization e.t.c) and the treatment regimen that is
           followed. As part of the visit, 20 mL of peripheral blood will be drawn prior to their
           treatment according to physician's suggestion as per common clinical practice. Blood
           samples will be then sent to ACTC laboratory for plasma/CTC isolation, DNA and RNA
           extraction and subsequent test for biomarkers. Primary tumor tissue samples will be also
           collected

        2. Follow-up visit (V1): Response to treatment by RECIST based on restaging CTs/MRIs will
           be documented during this visit, which will take place 3 months after treatment
           initiation. As part of the visit, 20 mL of peripheral blood will be drawn.

      Blood samples will be then sent to laboratory for plasma/CTC isolation, DNA and RNA
      extraction and subsequent test for biomarkers. Survival status and clinical response (CR, PR,
      SD, PD) will be also documented.
observational model: Other
time perspective: Prospective
measure: Clinical performance of PIK3CA kit in CTCs, plasma and tumor tissue samples of metastatic breast cancer patients
time frame: 18 months
description: The performance of PIK3CA kit on detecting mutations in CTCs samples of metastatic breast cancer patients will be assessed via Sensitivity, Specificity, Positive and Negative Predictive Values, Positive and Negative Likelihood Ratios, Accuracy and Diagnostic Odds Ratio. The point of primary evaluation in CTCs samples will be at baseline and droplet digital PCR will be used as reference method.
The performance of PIK3CA kit on detecting mutations in plasma-ctDNA, and tumor tissue samples of metastatic breast cancer patients will be assessed via Sensitivity, Specificity Positive and Negative Predictive Values, Positive and Negative Likelihood Ratios, Accuracy and Diagnostic Odds Ratio. The point of primary evaluation in plasma-ctDNA and tumor tissue samples will be at baseline and therascreen PIK3CA RGQ PCR Kit will be used as reference method.
measure: - To study the PIK3CA Mutation Status before and after treatment of metastatic breast cancer patients using PIK3CA kit.
time frame: 24 months
description: Presence of PIK3CA mutations at a second visit following to baseline of metastatic breast cancer patients using the PIK3CA kit.
measure: - To assess the PIK3CA Mutation Status before treatment vs treatment response of metastatic breast cancer patients using PIK3CA kit.
time frame: 24 months
description: Association of PIK3CA mutations presence at baseline with clinical response to treatment (CR, PR, SD, PD) of metastatic breast cancer patients using PIK3CA kit.
measure: - To correlate patients' survival status with PIK3CA mutations at baseline
time frame: 24 months
description: Metastatic breast cancer patients' survival status by presence of PIK3CA mutations at baseline.
measure: To study CK-19 expression in CTC samples
time frame: 24 months
description: Detection of CK-19 expression in CTCs
measure: To study methylation status of ESR1 in CTC, ctDNA and tumor tissue samples
time frame: 24 months
description: Methylation status of ESR1 in CTC, plasma and tumor samples
measure: To study the presence of other biomarkers in tissue and liquid biopsy sample (at baseline).
time frame: 24 months
description: Molecular profile of cancer biomarkers between tissue and peripheral blood samples
arm group label: Metastatic Breast Cancer
description: The study population are subjects with a confirmed diagnosis of ER+/HER2 metastatic Breast Cancer patient before the treatment initiation.
The selected inclusion/exclusion criteria have been set to include in the performance study appropriate population of interest, as broad as possible, but to exclude these subjects that have another current malignancy or any history of recent malignancy within 3 years.
arm group label: Healthy volunteers
description: In case of healthy volunteers only peripheral blood samples will be collected.
intervention type: Diagnostic Test
intervention name: PIK3CA kit
description: Prospective investigation of clinical samples for evaluation of IVD clinical performance
arm group label: Healthy volunteers
arm group label: Metastatic Breast Cancer
CTCs, plasma-ctDNA and primary tumor tissue samples
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
facility: 
country: Greece
responsible party type: Sponsor
mesh term: Breast Neoplasms