<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/NCT03042221</url>
  </required_header>
  <id_info>
    <org_study_id>15-2316.cc</org_study_id>
    <nct_id>NCT03042221</nct_id>
  </id_info>
  <brief_title>Early Rebiopsy to Identify Biomarkers of Tumor Cell Survival Following EGFR, ALK, ROS1 or BRAF TKI Therapy</brief_title>
  <official_title>Early Rebiopsy to Identify Mechanisms and Biomarkers of Tumor Cell Survival Following Targeted Therapy in Patients With EGFR, ALK, ROS1 or BRAF Mutations.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>Yes</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>
      A comparison of baseline tumor characteristics in oncogene-driven cancers to tumor&#xD;
      characteristics after early response to Tyrosine Kinase Inhibitor (TKI) targeted treatment&#xD;
      will allow identification of early adaptive mechanisms of cell survival. This will facilitate&#xD;
      targeting and termination of these survival/ resistance pathways before they develop with&#xD;
      rational combinations of therapeutic agents to improve outcomes.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 20, 2016</start_date>
  <completion_date type="Anticipated">September 30, 2027</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2026</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>gene expression changes</measure>
    <time_frame>baseline and 2 weeks (+/- 1 week) for each patient.</time_frame>
    <description>change from baseline of tumor gene expression profile at 2 weeks. Global gene expression data will be collected using RNAseq</description>
  </primary_outcome>
  <primary_outcome>
    <measure>protein expression change</measure>
    <time_frame>baseline and 2 weeks (+/- 1 week) for each patient.</time_frame>
    <description>change from baseline of protein gene expression profile at 2 weeks as measured by multiplex protein assay (proteins to be assayed include: e-cadherin, vimentin, fibronectin, CD4, CD8, CD14, CD16, CD206, PDL1, and CSF1R)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Depth of Response</measure>
    <time_frame>Study startup through 36 months</time_frame>
    <description>Correlation between the depths of tumor response (by RECIST v1.1) (percentage decrease in tumor size) with the presence of an EMT signature.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Evaluation of Adverse Events</measure>
    <time_frame>Study startup through 36 months</time_frame>
    <description>Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0</description>
  </other_outcome>
  <other_outcome>
    <measure>Success rate of Repeat Biopsy</measure>
    <time_frame>Study startup through 36 months</time_frame>
    <description>Success rate of early rebiopsy in obtaining tumor samples that have evaluable material for RNA Seq and other analyses</description>
  </other_outcome>
  <other_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>Study startup through 36 months</time_frame>
    <description>Length of PFS as per RECIST 1.1</description>
  </other_outcome>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Non-Small Cell Carcinoma of Lung, TNM Stage 4</condition>
  <condition>Non-Small Cell Lung Cancer</condition>
  <condition>EGFR Gene Mutation</condition>
  <condition>ALK Gene Mutation</condition>
  <condition>ROSE Cluster 1</condition>
  <condition>BRAF V600E</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Tumor tissue&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects who have a diagnosis of State IV Lung Adenocarcinoma with EGFR activating mutation&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Carry a diagnosis of stage IV lung adenocarcinoma with an activating mutation&#xD;
             determined to respond to an estimated glomerular filtration rate (EGFR) TKI, alkaline&#xD;
             phosphatase (ALK) or ROS Proto-Oncogene 1 (ROS1) fusion or BRAF V600E.&#xD;
&#xD;
          -  Aged 18 - 85 years or older&#xD;
&#xD;
          -  ECOG 0-2&#xD;
&#xD;
          -  Have a histologically confirmed diagnosis of lung adenocarcinoma harboring an EGFR&#xD;
             sensitizing mutation (including, but not limited to: G719X, del exon 19, or L858R).&#xD;
&#xD;
          -  No prior therapy for metastatic disease.&#xD;
&#xD;
          -  Planned treatment with a single agent EGFR TKI including but not limited to:&#xD;
&#xD;
               1. erlotinib,&#xD;
&#xD;
               2. gefitinib,&#xD;
&#xD;
               3. rociletinib (CO-1686),&#xD;
&#xD;
               4. afatinib, or&#xD;
&#xD;
               5. osimertinib (AZD-9291).&#xD;
&#xD;
          -  Patients must have at least one site of measurable disease ≥ least 2cm.&#xD;
&#xD;
          -  Primary disease site or site of metastatic disease must be amenable to biopsy.&#xD;
&#xD;
          -  Patients must have the ability to understand and willingness to sign an informed&#xD;
             consent document.&#xD;
&#xD;
          -  Patients must be willing to undergo an initial pre-treatment biopsy of tumor tissue&#xD;
             (or have previously collected frozen tissue) and a follow-up biopsy 2 weeks (+/- 1&#xD;
             week) after treatment start&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concurrent health problem which would preclude tissue biopsy (eg hemophilia or other&#xD;
             bleeding predisposition).&#xD;
&#xD;
          -  Patients whose only source of biopsiable disease is:&#xD;
&#xD;
               1. intracranial,&#xD;
&#xD;
               2. pleural effusion or any lesion that is deemed unsafe to biopsy by the treating&#xD;
                  physician or,&#xD;
&#xD;
               3. interventional radiology.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Erin Schenk</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Brandi Kubala</last_name>
    <phone>303-724-1657</phone>
    <email>brandi.kubala@cuanschutz.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Colorado, Cancer Center</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Brandi Kubala</last_name>
      <phone>303-724-1657</phone>
      <email>brandi.kubala@cuanschutz.edu</email>
    </contact>
    <contact_backup>
      <last_name>Erin Schenk</last_name>
      <phone>303-724-4304</phone>
      <email>erin.schenk@cuanschutz.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Erin Schenk</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>January 30, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>November 17, 2022</last_update_submitted>
  <last_update_submitted_qc>November 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Lung Neoplasms</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/NCT03042221
org study id: 15-2316.cc
nct id: NCT03042221
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A comparison of baseline tumor characteristics in oncogene-driven cancers to tumor
      characteristics after early response to Tyrosine Kinase Inhibitor (TKI) targeted treatment
      will allow identification of early adaptive mechanisms of cell survival. This will facilitate
      targeting and termination of these survival/ resistance pathways before they develop with
      rational combinations of therapeutic agents to improve outcomes.
observational model: Other
time perspective: Other
measure: gene expression changes
time frame: baseline and 2 weeks (+/- 1 week) for each patient.
description: change from baseline of tumor gene expression profile at 2 weeks. Global gene expression data will be collected using RNAseq
measure: protein expression change
time frame: baseline and 2 weeks (+/- 1 week) for each patient.
description: change from baseline of protein gene expression profile at 2 weeks as measured by multiplex protein assay (proteins to be assayed include: e-cadherin, vimentin, fibronectin, CD4, CD8, CD14, CD16, CD206, PDL1, and CSF1R)
measure: Depth of Response
time frame: Study startup through 36 months
description: Correlation between the depths of tumor response (by RECIST v1.1) (percentage decrease in tumor size) with the presence of an EMT signature.
measure: Evaluation of Adverse Events
time frame: Study startup through 36 months
description: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
measure: Success rate of Repeat Biopsy
time frame: Study startup through 36 months
description: Success rate of early rebiopsy in obtaining tumor samples that have evaluable material for RNA Seq and other analyses
measure: Progression Free Survival
time frame: Study startup through 36 months
description: Length of PFS as per RECIST 1.1
Tumor tissue
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Erin Schenk
role: Principal Investigator
affiliation: University of Colorado, Denver
last name: Brandi Kubala
phone: 303-724-1657
email: brandi.kubala@cuanschutz.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Lung Neoplasms
sharing ipd: No