<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/NCT01697163</url>
  </required_header>
  <id_info>
    <org_study_id>ISSIRES0067</org_study_id>
    <nct_id>NCT01697163</nct_id>
  </id_info>
  <brief_title>De Novo Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors</brief_title>
  <official_title>Pilot Study to Identify the Mechanism of De Novo Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) in NSCLC With EGFR Mutation.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Severance Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Severance Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is based on the following hypothesis &quot;De novo resistance to EGFR-TKI in EGFR&#xD;
      mutation positive patients is related with mutations in EGFR downstream genes&quot;.&#xD;
&#xD;
      Investigators will prospectively collect genomic DNA and clinical data regarding treatment&#xD;
      outcomes to EGFR-TKI in NSCLC patients with activating EGFR mutations. Investigators will&#xD;
      sequence candidate mutations of EGFR downstream genes and analyze c-met gene amplification&#xD;
      and protein expression in PTEN, HGF, and IGFR. To identify genetic mutations, amplification,&#xD;
      and protein over expression as predictive markers of treatment outcomes, investigators&#xD;
      analyzed the association of treatment outcomes with the presence of genetic alteration or&#xD;
      protein over expression. Investigators will attempt to identify biomarkers that are able to&#xD;
      predict de novo resistance to EGFR-TKI in EGFR mutated NSCLC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Investigators will prospectively enroll patients who match the following criteria:&#xD;
      pathologically proven unresectable NSCLC, planning to treat with EGFR-TKI, patients with&#xD;
      activating EGFR mutations, and available tissue sample for DNA extraction.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>October 2012</start_date>
  <completion_date type="Anticipated">September 2014</completion_date>
  <primary_completion_date type="Anticipated">September 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>hazard rates of PFS</measure>
    <time_frame>1year</time_frame>
    <description>The primary objective is to compare hazard rates of PFS in patients treated with Iressa between with and without any molecular aberrancy in EGFR-downstream genes/proteins.</description>
  </primary_outcome>
  <other_outcome>
    <measure>OS</measure>
    <time_frame>2years</time_frame>
    <description>Overall survival (OS) of EGFR-TKI according to each biomarker (i.e. PIK3CA, AKT, PTEN, and STK11 mutation and HGF, c-met, and IGFR amplification) Disease control rate (DCR) of EGFR-TKI according to each biomarker (i.e. PIK3CA, AKT, PTEN, and STK11 mutation and HGF, c-met, and IGFR amplification) Progression-free survival (PFS) of EGFR-TKI according to each biomarker (i.e. PIK3CA, AKT, PTEN, and STK11 mutation and HGF, c-met, and IGFR amplification)</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">155</enrollment>
  <condition>NSCLC</condition>
  <arm_group>
    <arm_group_label>Iressa</arm_group_label>
    <description>Lung cancer patients with EGFR mutation</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      DNA extracted from FFPE tissue sample&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        NSCLC patient with EGFR mutation&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Pathologically proven unresectable NSCLC&#xD;
&#xD;
          2. 20 years of age or older&#xD;
&#xD;
          3. Planned treatment with Iressa®&#xD;
&#xD;
          4. Patients with activating EGFR mutation (del 19, L858R)&#xD;
&#xD;
          5. Available detailed smoking history&#xD;
&#xD;
          6. Available tissue samples (archival tissue) for mutational or molecular analysis&#xD;
             (representative paraffin block or unstained sections from tumor diagnostic specimen&#xD;
             are mandatory)&#xD;
&#xD;
          7. Available blood sample&#xD;
&#xD;
          8. At least one lesion that is measurable according to the RECIST 1.1 criteria by CT or&#xD;
             MRI&#xD;
&#xD;
          9. Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. More than 3rd line treatment&#xD;
&#xD;
          2. Previously treated with other EGFR-TKI&#xD;
&#xD;
          3. Life expectancy of less than 12 weeks&#xD;
&#xD;
          4. Pregnant or lactating female&#xD;
&#xD;
          5. Any unresolved toxicity greater than CTC grade 2 (version 4.0) from previous anti&#xD;
             cancer treatment.&#xD;
&#xD;
          6. Unsuitable patient in this treatment as determined by doctor.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joo Hang Kim, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Severance Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Joo Hang Kim, MD, PhD</last_name>
    <phone>82-2-2228-8131</phone>
    <email>kjhang@yuhs.ac</email>
  </overall_contact>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 12, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <last_update_submitted>September 26, 2012</last_update_submitted>
  <last_update_submitted_qc>September 26, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 2, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Severance Hospital</investigator_affiliation>
    <investigator_full_name>Joo Hang Kim</investigator_full_name>
    <investigator_title>Severance Hospital</investigator_title>
  </responsible_party>
  <keyword>De Novo Resistance</keyword>
  <keyword>Iressa</keyword>
  <keyword>EGFR mutation</keyword>
  <keyword>lung cancer</keyword>
  <!-- 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/NCT01697163
org study id: ISSIRES0067
nct id: NCT01697163
lead sponsor: 
collaborator: 
has dmc: No
This study is based on the following hypothesis "De novo resistance to EGFR-TKI in EGFR
      mutation positive patients is related with mutations in EGFR downstream genes".

      Investigators will prospectively collect genomic DNA and clinical data regarding treatment
      outcomes to EGFR-TKI in NSCLC patients with activating EGFR mutations. Investigators will
      sequence candidate mutations of EGFR downstream genes and analyze c-met gene amplification
      and protein expression in PTEN, HGF, and IGFR. To identify genetic mutations, amplification,
      and protein over expression as predictive markers of treatment outcomes, investigators
      analyzed the association of treatment outcomes with the presence of genetic alteration or
      protein over expression. Investigators will attempt to identify biomarkers that are able to
      predict de novo resistance to EGFR-TKI in EGFR mutated NSCLC.
Investigators will prospectively enroll patients who match the following criteria:
      pathologically proven unresectable NSCLC, planning to treat with EGFR-TKI, patients with
      activating EGFR mutations, and available tissue sample for DNA extraction.
time perspective: Prospective
measure: hazard rates of PFS
time frame: 1year
description: The primary objective is to compare hazard rates of PFS in patients treated with Iressa between with and without any molecular aberrancy in EGFR-downstream genes/proteins.
measure: OS
time frame: 2years
description: Overall survival (OS) of EGFR-TKI according to each biomarker (i.e. PIK3CA, AKT, PTEN, and STK11 mutation and HGF, c-met, and IGFR amplification) Disease control rate (DCR) of EGFR-TKI according to each biomarker (i.e. PIK3CA, AKT, PTEN, and STK11 mutation and HGF, c-met, and IGFR amplification) Progression-free survival (PFS) of EGFR-TKI according to each biomarker (i.e. PIK3CA, AKT, PTEN, and STK11 mutation and HGF, c-met, and IGFR amplification)
arm group label: Iressa
description: Lung cancer patients with EGFR mutation
DNA extracted from FFPE tissue sample
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: No
last name: Joo Hang Kim, MD, PhD
role: Principal Investigator
affiliation: Severance Hospital
last name: Joo Hang Kim, MD, PhD
phone: 82-2-2228-8131
email: kjhang@yuhs.ac
responsible party type: Principal Investigator
investigator affiliation: Severance Hospital
investigator full name: Joo Hang Kim
investigator title: Severance Hospital