<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/NCT04490564</url>
  </required_header>
  <id_info>
    <org_study_id>CBS-PD-L1a</org_study_id>
    <nct_id>NCT04490564</nct_id>
  </id_info>
  <brief_title>Validation of Molecular Diagnostic Assays to Detect Cancer Biomarkers in Blood and Primary Tumor in HNSCC/NSCLC/Melanoma</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 of Patients With Recurrent/Metastatic HNSCC, NSCLC or Melanoma.</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): All patients will provide a 10 mL peripheral blood sample during&#xD;
           their planned visit at the end of a series of immunotherapy cycles as per clinical&#xD;
           practice and physician's judgment. More specifically:&#xD;
&#xD;
           For HNSCC/NSCLC: at the end of four (4) treatment cycles with nivolumab (2 months) or at&#xD;
           the end of three (3) treatment cycles with pembrolizumab (2 months) or on disease&#xD;
           progress (PD) For melanoma: at 6 months after treatment initiation (antiPD-1) Blood&#xD;
           samples will be then sent to laboratory for plasma/CTC isolation, DNA and RNA extraction&#xD;
           and subsequent test for biomarkers. Clinical response (CR, PR, SD, PD) will be also&#xD;
           documented.&#xD;
&#xD;
        3. Follow-up visit (V2): All patients will provide a 10 mL peripheral blood sample on&#xD;
           progress of the disease or at the end of the observation period, as diagnosed during&#xD;
           their planned visit as per clinical practice and physician's judgment. Blood samples&#xD;
           will be then sent to laboratory&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 25, 2019</start_date>
  <completion_date type="Anticipated">June 25, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 25, 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 PD-L1 kit in CTCs of peripheral blood and tumor tissue samples</measure>
    <time_frame>12 months</time_frame>
    <description>The performance of PD-L1 kit at baseline in CTCs (using IF as reference method) and tumor tissue samples (using IHC as reference method) will be assessed via Sensitivity, Specificity, Positive and Negative Predictive Values, Positive and Negative Likelihood Ratios, Accuracy and Diagnostic Odds Ratio.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To study correlations between PD-L1 expression in serial liquid samples with patients' responsiveness to therapy.</measure>
    <time_frame>18 months</time_frame>
    <description>Clinical response to the selected treatment (CR, PR, SD, PD)&#xD;
Survival status</description>
  </secondary_outcome>
  <other_outcome>
    <measure>To study mutation status of BRAF gene in tumor tissue samples and blood samples (CTC, plasma ctDNA) of metastatic melanoma patients</measure>
    <time_frame>18 months</time_frame>
    <description>Mutation profile of BRAF in CTCs, plasma-ctDNA and tumor tissues of metastatic melanoma patients will be evaluated using PCR-molecular assays</description>
  </other_outcome>
  <other_outcome>
    <measure>To study the presence of biomarkers in tumor tissue and blood liquid biopsy samples (at baseline).</measure>
    <time_frame>18 months</time_frame>
    <description>Molecular profile of cancer biomarkers in tumor tissue and peripheral blood samples will be evaluated using PCR-molecular assays</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">185</enrollment>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <condition>Non Small Cell Lung Cancer</condition>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>HNSCC, NSCLC, melanoma Patients</arm_group_label>
    <description>The study population are subjects with a confirmed diagnosis of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), who are going to receive PD-1 inhibitor nivolumab or ii) metastatic Non-Small Cell Lung Cancer (NSCLC), who are going to receive PD-1 inhibitor, e.g. nivolumab, pembrolizumab or iii) metastatic melanoma, who are going to receive PD-1 inhibitor, e.g. nivolumab, embrolizumab. 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 healhty volunteers, only peripheral blood samples will be collected.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>PD-L1 Kit</intervention_name>
    <description>Clinical performance of PD-L1 kit in CTCs of peripheral blood and tumor tissue samples</description>
    <arm_group_label>HNSCC, NSCLC, melanoma Patients</arm_group_label>
    <arm_group_label>Healthy volunteers</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      CTCs of peripheral blood and primary tumor tissue (FFPEs) samples.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        155 subjects as follows: 25 patients with metastatic/recurrent HNSCC 120 patients with&#xD;
        metastatic NSCLC 10 patients with metastatic melanoma 30 healthy subjects&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female aged ≥ 18 years of age.&#xD;
&#xD;
          2. Patients with a diagnosis of&#xD;
&#xD;
               1. recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), who are&#xD;
                  going to receive PD-1 inhibitor nivolumab OR&#xD;
&#xD;
               2. metastatic Non-Small Cell Lung Cancer (NSCLC), who are going to receive PD-1&#xD;
                  inhibitor, e.g. nivolumab, pembrolizumab,OR&#xD;
&#xD;
               3. metastatic melanoma, who are going to receive to receive PD-1 inhibitor, e.g.&#xD;
                  nivolumab, pembrolizumab.&#xD;
&#xD;
          3. Available tumor tissue sample for immunohistochemical and molecular analysis.&#xD;
&#xD;
          4. Life expectancy ≥ 4 months.&#xD;
&#xD;
          5. Signed informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Male or 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>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sotiria Thoracic Diseases Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <state>Attica</state>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <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>Attika</state>
        <zip>124 62</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bioclinic</name>
      <address>
        <city>Thessaloníki</city>
        <state>Thessaloniki</state>
        <zip>546 22</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 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 29, 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>PD-L1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</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/NCT04490564
org study id: CBS-PD-L1a
nct id: NCT04490564
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): All patients will provide a 10 mL peripheral blood sample during
           their planned visit at the end of a series of immunotherapy cycles as per clinical
           practice and physician's judgment. More specifically:

           For HNSCC/NSCLC: at the end of four (4) treatment cycles with nivolumab (2 months) or at
           the end of three (3) treatment cycles with pembrolizumab (2 months) or on disease
           progress (PD) For melanoma: at 6 months after treatment initiation (antiPD-1) Blood
           samples will be then sent to laboratory for plasma/CTC isolation, DNA and RNA extraction
           and subsequent test for biomarkers. Clinical response (CR, PR, SD, PD) will be also
           documented.

        3. Follow-up visit (V2): All patients will provide a 10 mL peripheral blood sample on
           progress of the disease or at the end of the observation period, as diagnosed during
           their planned visit as per clinical practice and physician's judgment. Blood samples
           will be then sent to laboratory
observational model: Other
time perspective: Prospective
measure: Clinical performance of PD-L1 kit in CTCs of peripheral blood and tumor tissue samples
time frame: 12 months
description: The performance of PD-L1 kit at baseline in CTCs (using IF as reference method) and tumor tissue samples (using IHC as reference method) will be assessed via Sensitivity, Specificity, Positive and Negative Predictive Values, Positive and Negative Likelihood Ratios, Accuracy and Diagnostic Odds Ratio.
measure: To study correlations between PD-L1 expression in serial liquid samples with patients' responsiveness to therapy.
time frame: 18 months
description: Clinical response to the selected treatment (CR, PR, SD, PD)
Survival status
measure: To study mutation status of BRAF gene in tumor tissue samples and blood samples (CTC, plasma ctDNA) of metastatic melanoma patients
time frame: 18 months
description: Mutation profile of BRAF in CTCs, plasma-ctDNA and tumor tissues of metastatic melanoma patients will be evaluated using PCR-molecular assays
measure: To study the presence of biomarkers in tumor tissue and blood liquid biopsy samples (at baseline).
time frame: 18 months
description: Molecular profile of cancer biomarkers in tumor tissue and peripheral blood samples will be evaluated using PCR-molecular assays
arm group label: HNSCC, NSCLC, melanoma Patients
description: The study population are subjects with a confirmed diagnosis of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), who are going to receive PD-1 inhibitor nivolumab or ii) metastatic Non-Small Cell Lung Cancer (NSCLC), who are going to receive PD-1 inhibitor, e.g. nivolumab, pembrolizumab or iii) metastatic melanoma, who are going to receive PD-1 inhibitor, e.g. nivolumab, embrolizumab. 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 healhty volunteers, only peripheral blood samples will be collected.
intervention type: Diagnostic Test
intervention name: PD-L1 Kit
description: Clinical performance of PD-L1 kit in CTCs of peripheral blood and tumor tissue samples
arm group label: HNSCC, NSCLC, melanoma Patients
arm group label: Healthy volunteers
CTCs of peripheral blood and primary tumor tissue (FFPEs) samples.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Greece
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Squamous Cell Carcinoma of Head and Neck