<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/NCT02230553</url>
  </required_header>
  <id_info>
    <org_study_id>NL49551.031.14</org_study_id>
    <nct_id>NCT02230553</nct_id>
  </id_info>
  <brief_title>Lapatinib Plus Trametinib in KRAS Mutant NSCLC</brief_title>
  <acronym>M14LTK</acronym>
  <official_title>Phase I/II Study With Lapatinib Plus Trametinib in Patients With Metastatic KRAS Mutant Non-small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Netherlands Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The Netherlands Cancer Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label phase I/II multi-center study consisting of two parts. Part A of this&#xD;
      study is designed to identify the recommended phase 2 dose (RP2D) of lapatinib combined with&#xD;
      trametinib in patients with metastatic KRASm and PIK3CA wild-type (PIK3CAwt) non-small cell&#xD;
      lung cancer (NSCLC). Part B is designed to perform a randomized comparison of the&#xD;
      lapatinib-trametinib combination versus standard of care therapy in patients with metastatic&#xD;
      KRASm/PIK3CAwt NSCLC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">August 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence rate of dose-limiting toxicities</measure>
    <time_frame>1.5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>progression free survival</measure>
    <time_frame>2.5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>overall response rate</measure>
    <time_frame>2.5 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of adveres events</measure>
    <time_frame>2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration</measure>
    <time_frame>2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response</measure>
    <time_frame>2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>lapatinib + trametinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>lapatinib: oral tablets, once daily trametinib: oral tablets, once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lapatinib</intervention_name>
    <arm_group_label>lapatinib + trametinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>trametinib</intervention_name>
    <arm_group_label>lapatinib + trametinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological or cytological proof of metastatic NSCLC; for PART B: treated with first&#xD;
             line therapy for metastatic disease only.&#xD;
&#xD;
          -  Written documentation of a known pathogenic KRAS (exon 2, 3 or 4) mutation and PIK3CA&#xD;
             wild-type (exon 9 and 20)&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Able and willing to give written informed consent&#xD;
&#xD;
          -  WHO performance status of 0 or 1 (part A and B)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any treatment with investigational drugs within 30 days prior to receiving the first&#xD;
             dose of investigational treatment.&#xD;
&#xD;
          -  History of another primary malignancy&#xD;
&#xD;
          -  Symptomatic or untreated leptomeningeal disease&#xD;
&#xD;
          -  Symptomatic brain metastasis&#xD;
&#xD;
          -  History of interstitial lung disease or pneumonitis&#xD;
&#xD;
          -  Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2&#xD;
             type patients&#xD;
&#xD;
          -  Retinal degenerative disease (hereditary retinal degeneration or age-related macular&#xD;
             degeneration), or a history of uveitis, retinal vein occlusion, central serous&#xD;
             retinopathy, or retinal detachment&#xD;
&#xD;
          -  Patients with left ventricular ejection fraction (LVEF) &lt; 50%&#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>F Opdam, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>The Netherlands Cancer Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>F Opdam, MD,PhD</last_name>
    <phone>0031205122446</phone>
    <email>f.opdam@nki.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>S Huijberts, MD</last_name>
    <phone>0031205129111</phone>
    <email>s.huijberts@nki.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Netherlands Cancer Institute</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>N HM Steeghs, MD, PhD</last_name>
      <phone>0031205122446</phone>
      <email>n.steeghs@nki.nl</email>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>August 29, 2014</study_first_submitted>
  <study_first_submitted_qc>August 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <last_update_submitted>August 29, 2018</last_update_submitted>
  <last_update_submitted_qc>August 29, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2018</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>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lapatinib</mesh_term>
    <mesh_term>Trametinib</mesh_term>
  </intervention_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/NCT02230553
org study id: NL49551.031.14
nct id: NCT02230553
lead sponsor: 
collaborator: 
has dmc: No
This is an open-label phase I/II multi-center study consisting of two parts. Part A of this
      study is designed to identify the recommended phase 2 dose (RP2D) of lapatinib combined with
      trametinib in patients with metastatic KRASm and PIK3CA wild-type (PIK3CAwt) non-small cell
      lung cancer (NSCLC). Part B is designed to perform a randomized comparison of the
      lapatinib-trametinib combination versus standard of care therapy in patients with metastatic
      KRASm/PIK3CAwt NSCLC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence rate of dose-limiting toxicities
time frame: 1.5 years
measure: progression free survival
time frame: 2.5 years
measure: overall response rate
time frame: 2.5 years
measure: Incidence and severity of adveres events
time frame: 2.5 years
measure: Plasma concentration
time frame: 2.5 years
measure: Duration of response
time frame: 2.5 years
measure: Time to response
time frame: 2.5 years
measure: Overall survival
time frame: 3 years
arm group label: lapatinib + trametinib
arm group type: Experimental
description: lapatinib: oral tablets, once daily trametinib: oral tablets, once daily
intervention type: Drug
intervention name: Lapatinib
arm group label: lapatinib + trametinib
intervention type: Drug
intervention name: trametinib
arm group label: lapatinib + trametinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: F Opdam, MD, PhD
role: Study Director
affiliation: The Netherlands Cancer Institute
last name: F Opdam, MD,PhD
phone: 0031205122446
email: f.opdam@nki.nl
last name: S Huijberts, MD
phone: 0031205129111
email: s.huijberts@nki.nl
facility: 
status: Recruiting
contact: 
country: Netherlands
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Lapatinib
mesh term: Trametinib