<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/NCT03755102</url>
  </required_header>
  <id_info>
    <org_study_id>18-341</org_study_id>
    <nct_id>NCT03755102</nct_id>
  </id_info>
  <brief_title>A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progression on Osimertinib.</brief_title>
  <official_title>A Pilot Study of Dacomitinib With or Without Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers With Disease Progressionon Osimertinib.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess whether dacomitinib after osimertinib is effective in&#xD;
      participants with metastatic EGR-mutant lung cancers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 21, 2018</start_date>
  <completion_date type="Actual">July 7, 2023</completion_date>
  <primary_completion_date type="Actual">July 7, 2023</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>1 year</time_frame>
    <description>Overall response rate (partial and complete responses) of dacomitinib in participants with EGFR-mutant lung cancers and disease progression on osimertinib</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>EGFR Gene Mutation</condition>
  <condition>Lung Cancer</condition>
  <condition>Lung Cancer Metastatic</condition>
  <arm_group>
    <arm_group_label>Cohort 1: Participants treated with dacomitinib alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this cohort have a somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: Participants treated with dacomitinib in combination with osimertinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this cohort have a secondary acquired EGFR mutation in addition to the sensitizing mutation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dacomitinib</intervention_name>
    <description>Cohort 1 Dacomitinib Dosing:&#xD;
Dose level 1: Dacomitinib 45mg daily Dose level -1: Dacomitinib 30mg daily Dose level -2: Dacomitinib 15mg daily&#xD;
Cohort 2 Dacomitinib Dosing:&#xD;
Dose level 1: Dacomitinib 30 mg daily Dose level -1: Dacomitinib 15 mg daily</description>
    <arm_group_label>Cohort 1: Participants treated with dacomitinib alone</arm_group_label>
    <arm_group_label>Cohort 2: Participants treated with dacomitinib in combination with osimertinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Osimertinib</intervention_name>
    <description>In cohort 2, participants will begin on dacomitinib orally daily in combination with Osimertinib&#xD;
Dose level Osimertinib Dosing:&#xD;
Dose level 1: Osimertinib 80 mg daily Dose level -1: Osimertinib 40 mg daily</description>
    <arm_group_label>Cohort 2: Participants treated with dacomitinib in combination with osimertinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Advanced biopsy-proven metastatic non-small cell lung cancer&#xD;
&#xD;
          -  Somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy&#xD;
&#xD;
          -  Prior treatment with osimertinib with response followed by disease progression&#xD;
&#xD;
          -  No prior first or second generation EGFR inhibitor treatment (gefitinib, afatinib,&#xD;
             erlotinib)&#xD;
&#xD;
          -  Archival tissue available from a tumor biopsy done after disease progression on&#xD;
             osimertinib or willing to undergo a tumor biopsy or liquid biopsy after disease&#xD;
             progression on osimertinib prior to study initiation&#xD;
&#xD;
          -  Measurable (RECIST 1.1) indicator lesion not previously irradiated&#xD;
&#xD;
          -  Karnofsky performance status (KPS) &gt;/= 70%&#xD;
&#xD;
          -  Age &gt;/= 18 years old&#xD;
&#xD;
          -  Ability to swallow oral medication&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
               -  AST, ALT &lt;/= 3 x ULN&#xD;
&#xD;
               -  Total bilirubin &lt;/= 1.5x ULN&#xD;
&#xD;
               -  Creatinine &lt;/= 1.5x ULN OR calculated creatinine clearance &gt;/= 60ml/min&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) &gt;/= 1000 cells/mm3&#xD;
&#xD;
               -  Hemoglobin&gt;/=8.0 g/dL&#xD;
&#xD;
               -  Platelets &gt;/=75,000/mm3&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Any radiotherapy within 1 week of starting treatment on protocol.&#xD;
&#xD;
          -  Any major surgery within 1 weeks of starting treatment on protocol.&#xD;
&#xD;
          -  Any evidence of active clinically significant interstitial lung disease&#xD;
&#xD;
          -  Continue to have unresolved &gt; grade 1 toxicity from any previous treatment Treatment&#xD;
&#xD;
          -  Patients with a known mechanism of resistance to osimertinib that will clearly not&#xD;
             respond to dacomitinib therapy (i.e. known MET amplification, ALK fusion, RET fusion).&#xD;
&#xD;
          -  Symptomatic brain metastases or leptomeningeal disease requiring escalating doses of&#xD;
             steroids&#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>Helen Yu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Basking Ridge</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Commack</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Rockville Centre</name>
      <address>
        <city>Rockville Centre</city>
        <state>New York</state>
        <zip>11570</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Nassau</name>
      <address>
        <city>Uniondale</city>
        <state>New York</state>
        <zip>11553</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>July 10, 2023</last_update_submitted>
  <last_update_submitted_qc>July 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>EGFR C797S</keyword>
  <keyword>EGFR mutant lung cancer</keyword>
  <keyword>dacomitinib</keyword>
  <keyword>osimertinib</keyword>
  <keyword>18-341</keyword>
  <keyword>Memorial Sloan Kettering Cancer Center</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osimertinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</ipd_description>
  </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/NCT03755102
org study id: 18-341
nct id: NCT03755102
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to assess whether dacomitinib after osimertinib is effective in
      participants with metastatic EGR-mutant lung cancers.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate
time frame: 1 year
description: Overall response rate (partial and complete responses) of dacomitinib in participants with EGFR-mutant lung cancers and disease progression on osimertinib
measure: Progression-free survival
time frame: 1 year
measure: Overall survival
time frame: 1 year
arm group label: Cohort 1: Participants treated with dacomitinib alone
arm group type: Experimental
description: Participants in this cohort have a somatic activating mutation in EGFR in a tumor biopsy or plasma cfDNA liquid biopsy.
arm group label: Cohort 2: Participants treated with dacomitinib in combination with osimertinib
arm group type: Experimental
description: Participants in this cohort have a secondary acquired EGFR mutation in addition to the sensitizing mutation
intervention type: Drug
intervention name: Dacomitinib
description: Cohort 1 Dacomitinib Dosing:
Dose level 1: Dacomitinib 45mg daily Dose level -1: Dacomitinib 30mg daily Dose level -2: Dacomitinib 15mg daily
Cohort 2 Dacomitinib Dosing:
Dose level 1: Dacomitinib 30 mg daily Dose level -1: Dacomitinib 15 mg daily
arm group label: Cohort 1: Participants treated with dacomitinib alone
arm group label: Cohort 2: Participants treated with dacomitinib in combination with osimertinib
intervention type: Drug
intervention name: Osimertinib
description: In cohort 2, participants will begin on dacomitinib orally daily in combination with Osimertinib
Dose level Osimertinib Dosing:
Dose level 1: Osimertinib 80 mg daily Dose level -1: Osimertinib 40 mg daily
arm group label: Cohort 2: Participants treated with dacomitinib in combination with osimertinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Helen Yu, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Osimertinib
sharing ipd: Yes
ipd description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.