<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/NCT03248089</url>
  </required_header>
  <id_info>
    <org_study_id>MedOPP125</org_study_id>
    <nct_id>NCT03248089</nct_id>
  </id_info>
  <brief_title>Spanish Lung Liquid vs. Invasive Biopsy Program (SLLIP)</brief_title>
  <acronym>SLLIP</acronym>
  <official_title>Spanish Lung Liquid vs. Invasive Biopsy Program</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MedSIR</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Guardant Health, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>MedSIR</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      Tumor Derived cell free DNA (cfDNA) is increasingly used in the clinic to obtain genotype&#xD;
      information about lung cancer, but its concordance with concurrent tumor-derived sequenced&#xD;
      data is not known. The primary objective of this study is to demonstrate the non-inferiority&#xD;
      of cfDNA-based versus tumor tissue-based genotyping.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary objective:&#xD;
&#xD;
      To demonstrate the non-inferiority of cfDNA-based versus tumor tissue-based genotyping as it&#xD;
      pertains to the detection of clinically-actionable biomarkers in first line, treatment naïve,&#xD;
      metastatic non-squamous NSCLC.&#xD;
&#xD;
      The following secondary objectives will be studied:&#xD;
&#xD;
        -  Turn around Time (TAT) of cfDNA vs. tissue results.&#xD;
&#xD;
        -  Time to treatment (TtT) initiation.&#xD;
&#xD;
        -  Quantity not sufficient rate (QNS) of tissue for clinically-actionable biomarker&#xD;
           testing.&#xD;
&#xD;
        -  Tumor Not Detected (TND) rate of cfDNA in blood.&#xD;
&#xD;
        -  Rescue rate of QNS samples using cfDNA-derived genotyping.&#xD;
&#xD;
        -  Rate response for patients that are actionable biomarker positive (either in cDNA or&#xD;
           tissue) treated with target-drugs according investigator criteria. Up to three RECIST&#xD;
           assessments per patient will be retrospectively done by external personnel (no&#xD;
           investigational team).&#xD;
&#xD;
        -  Rate of discovery of genomically mediated, acquired resistance to targeted therapies in&#xD;
           the biomarker-positive subsets.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2016</start_date>
  <completion_date type="Actual">January 2019</completion_date>
  <primary_completion_date type="Actual">July 2017</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>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Non-inferiority of cell free DNA (cfDNA)-based versus tumor tissue-based genotyping</measure>
    <time_frame>From date of inclusion until 12 months from enrollment follow-up or upon progression, death or withdrawal from study participation, whichever occurs first.</time_frame>
    <description>Demonstrate the non-inferiority of cell free DNA (cfDNA)-based versus tumor tissue-based genotyping as it pertains to the detection of clinically-actionable biomarkers in first line, treatment naïve, metastatic non-squamous Non-small cell lung cancer (NSCLC).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Turn around Time (TAT) of cell free DNA (cfDNA) vs. tissue results</measure>
    <time_frame>From pre-treatment visit until month 12 or upon progression, whichever occurs first</time_frame>
    <description>Turn around Time (TAT) of cell free DNA (cfDNA) vs. tissue results</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to treatment (TtT) initiation</measure>
    <time_frame>From the date of enrollment in the study until D1 (treatment initiation)</time_frame>
    <description>Time to treatment (TtT) initiation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantity not sufficient rate (QNS) of tissue</measure>
    <time_frame>From day 0 to pre-treatment visit</time_frame>
    <description>Quantity not sufficient rate (QNS) of tissue for clinically-actionable biomarker testing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tissue Incomplete (TI) rate of tissue</measure>
    <time_frame>From day 0 to pre-treatment visit</time_frame>
    <description>Tissue Incomplete (TI) rate of tissue for National Cancer Center Network (NCCN) biomarker testing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor Not Detected (TND) rate of cell free DNA (cfDNA)</measure>
    <time_frame>From pre-treatment visit until month 12 or upon progression, whichever occurs first</time_frame>
    <description>Tumor Not Detected (TND) rate of cell free DNA (cfDNA) in blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue rate of Quantity not sufficient (QNS) samples using cell free DNA (cfDNA)-derived genotyping</measure>
    <time_frame>From pre-treatment visit until month 12 or upon progression, whichever occurs first</time_frame>
    <description>Rescue rate of Quantity not sufficient (QNS) samples using cell free DNA (cfDNA)-derived genotyping</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate response for patients that are actionable biomarker positive (either in cell DNA (cDNA) or tissue) treated with target-drugs</measure>
    <time_frame>From visit 0 until month 12 or upon progression, whichever occurs first</time_frame>
    <description>Rate response for patients that are actionable biomarker positive (either in cell DNA (cDNA) or tissue) treated with target-drugs according investigator criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of discovery of genomically mediated, acquired resistance to targeted therapies</measure>
    <time_frame>From visit 0 until month 12 or upon progression, whichever occurs first</time_frame>
    <description>Rate of discovery of genomically mediated, acquired resistance to targeted therapies in the biomarker-positive subsets.</description>
  </secondary_outcome>
  <enrollment type="Actual">186</enrollment>
  <condition>Lung Cancer</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Guardant360</intervention_name>
    <description>Cell-free circulating tumor DNA (cfDNA) targeted next-generation sequencing (NGS) panel.</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Approximately 20 mL of peripheral blood will be collected in StreckTM tubeS. cfDNA will be&#xD;
      drawn following blood withdraws following standard of care of the participating site, which&#xD;
      would be, before treatment (v2); on the same date as the first standard of care labs (V3),&#xD;
      which would be approximately 2 weeks (14 days) into first-line treatment and after one year&#xD;
      from enrollment or upon progression whichever occurs first (EoS visit).&#xD;
&#xD;
      enrollment or upon progression whichever occurs first (EoS visit).&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        182 patients with previously untreated non-small cell lung cancer (NSCLC), non-squamous&#xD;
        subtype will be recruited for this study, wherein Cell free DNA (cfDNA) will be compared to&#xD;
        biopsy-based tumor sequencing&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients biopsy-proven, metastatic, previously untreated, non-squamous non-small cell&#xD;
             lung cancer (NSCLC). Patients may have received adjuvant cytotoxic chemotherapy, but&#xD;
             not targeted neo-adjuvant or adjuvant therapy.&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Ability to understand a written informed consent document, and the willingness to sign&#xD;
             it.&#xD;
&#xD;
          -  Willingness to provide blood sample at the time points defined in Table 1&#xD;
             [pre-treatment, Day 14 (+/- 7 days) and End of Study].&#xD;
&#xD;
          -  Patient has or will have standard-of-care tissue genotyping ordered.&#xD;
&#xD;
          -  Stable Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy, recorded from clinical records&#xD;
&#xD;
          -  Any concurrent, non-cutaneous, malignancy (with the exception of early stage&#xD;
             non-invasive cervical cancer). Any prior cancer must have occurred more than 5 years&#xD;
             prior with no evidence of currently active disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rafael Rosell</last_name>
    <role>Principal Investigator</role>
    <affiliation>IOR</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>H. Can Ruti</name>
      <address>
        <city>Badalona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dexeus</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. del Mar</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Vall Hebrón</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO Bellvitge</name>
      <address>
        <city>L'Hospitalet de Llobregat</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Arnau de Vilanova</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <last_update_submitted>January 8, 2019</last_update_submitted>
  <last_update_submitted_qc>January 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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/NCT03248089
org study id: MedOPP125
nct id: NCT03248089
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
Tumor Derived cell free DNA (cfDNA) is increasingly used in the clinic to obtain genotype
      information about lung cancer, but its concordance with concurrent tumor-derived sequenced
      data is not known. The primary objective of this study is to demonstrate the non-inferiority
      of cfDNA-based versus tumor tissue-based genotyping.
Primary objective:

      To demonstrate the non-inferiority of cfDNA-based versus tumor tissue-based genotyping as it
      pertains to the detection of clinically-actionable biomarkers in first line, treatment naïve,
      metastatic non-squamous NSCLC.

      The following secondary objectives will be studied:

        -  Turn around Time (TAT) of cfDNA vs. tissue results.

        -  Time to treatment (TtT) initiation.

        -  Quantity not sufficient rate (QNS) of tissue for clinically-actionable biomarker
           testing.

        -  Tumor Not Detected (TND) rate of cfDNA in blood.

        -  Rescue rate of QNS samples using cfDNA-derived genotyping.

        -  Rate response for patients that are actionable biomarker positive (either in cDNA or
           tissue) treated with target-drugs according investigator criteria. Up to three RECIST
           assessments per patient will be retrospectively done by external personnel (no
           investigational team).

        -  Rate of discovery of genomically mediated, acquired resistance to targeted therapies in
           the biomarker-positive subsets.
observational model: Other
time perspective: Other
measure: Non-inferiority of cell free DNA (cfDNA)-based versus tumor tissue-based genotyping
time frame: From date of inclusion until 12 months from enrollment follow-up or upon progression, death or withdrawal from study participation, whichever occurs first.
description: Demonstrate the non-inferiority of cell free DNA (cfDNA)-based versus tumor tissue-based genotyping as it pertains to the detection of clinically-actionable biomarkers in first line, treatment naïve, metastatic non-squamous Non-small cell lung cancer (NSCLC).
measure: Turn around Time (TAT) of cell free DNA (cfDNA) vs. tissue results
time frame: From pre-treatment visit until month 12 or upon progression, whichever occurs first
description: Turn around Time (TAT) of cell free DNA (cfDNA) vs. tissue results
measure: Time to treatment (TtT) initiation
time frame: From the date of enrollment in the study until D1 (treatment initiation)
description: Time to treatment (TtT) initiation
measure: Quantity not sufficient rate (QNS) of tissue
time frame: From day 0 to pre-treatment visit
description: Quantity not sufficient rate (QNS) of tissue for clinically-actionable biomarker testing
measure: Tissue Incomplete (TI) rate of tissue
time frame: From day 0 to pre-treatment visit
description: Tissue Incomplete (TI) rate of tissue for National Cancer Center Network (NCCN) biomarker testing
measure: Tumor Not Detected (TND) rate of cell free DNA (cfDNA)
time frame: From pre-treatment visit until month 12 or upon progression, whichever occurs first
description: Tumor Not Detected (TND) rate of cell free DNA (cfDNA) in blood
measure: Rescue rate of Quantity not sufficient (QNS) samples using cell free DNA (cfDNA)-derived genotyping
time frame: From pre-treatment visit until month 12 or upon progression, whichever occurs first
description: Rescue rate of Quantity not sufficient (QNS) samples using cell free DNA (cfDNA)-derived genotyping
measure: Rate response for patients that are actionable biomarker positive (either in cell DNA (cDNA) or tissue) treated with target-drugs
time frame: From visit 0 until month 12 or upon progression, whichever occurs first
description: Rate response for patients that are actionable biomarker positive (either in cell DNA (cDNA) or tissue) treated with target-drugs according investigator criteria.
measure: Rate of discovery of genomically mediated, acquired resistance to targeted therapies
time frame: From visit 0 until month 12 or upon progression, whichever occurs first
description: Rate of discovery of genomically mediated, acquired resistance to targeted therapies in the biomarker-positive subsets.
intervention type: Diagnostic Test
intervention name: Guardant360
description: Cell-free circulating tumor DNA (cfDNA) targeted next-generation sequencing (NGS) panel.
Approximately 20 mL of peripheral blood will be collected in StreckTM tubeS. cfDNA will be
      drawn following blood withdraws following standard of care of the participating site, which
      would be, before treatment (v2); on the same date as the first standard of care labs (V3),
      which would be approximately 2 weeks (14 days) into first-line treatment and after one year
      from enrollment or upon progression whichever occurs first (EoS visit).

      enrollment or upon progression whichever occurs first (EoS visit).
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rafael Rosell
role: Principal Investigator
affiliation: IOR
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Spain
responsible party type: Sponsor
sharing ipd: No