<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/NCT03810807</url>
  </required_header>
  <id_info>
    <org_study_id>18-411</org_study_id>
    <nct_id>NCT03810807</nct_id>
  </id_info>
  <brief_title>Study of Dacomitinib and Osimertinib for Patients With Advanced EGFR Mutant Lung Cancer</brief_title>
  <official_title>Phase 1 Study of Combination Dacomitinib and Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers</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 test the safety of dacomitinib and osimertinib, at increasing&#xD;
      doses, to find out what effects, if any, this combination of drugs has on people with&#xD;
      metastatic EGFR mutant lung cancer that has not been treated with an EGFR TKI.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 17, 2019</start_date>
  <completion_date type="Anticipated">January 2024</completion_date>
  <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <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>maximum tolerated dose</measure>
    <time_frame>1 year</time_frame>
    <description>The MTD will be defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity (DLT). DLT is defined as any of the toxicity events described below that occurs within cycle 1 of treatment with the combination of dacomitinib and osimertinib.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Best overall response rate</measure>
    <time_frame>1 year</time_frame>
    <description>Tumor response will be assessed using RECIST 1.1.The NCI Common Terminology Criteria for Adverse Events Version 5 (NCI-CTCAE) will be used to grade toxicities during the trial. Dose-limiting toxicities (DLT&quot;s) are defined as any of the following events occurring during the first cycle of treatment</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Metastatic Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Dacomitinib and Osimertinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will begin on combination dacomitinib and osimertinib at the prescribed doses.&#xD;
A cycle will be 28 days in duration. The study will use a standard 3+3 dose escalation design. Per MD discretion, telemedicine visits may be utilized for cycles where imaging is not collected, and physical exam, vital sign and labs collection will only be required concurrent with imaging visits.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dacomitinib</intervention_name>
    <description>Dose level 1 Dacomitinib, Dose level 2 Dacomitinib, Dose level 3 Dacomitinib. Three patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.</description>
    <arm_group_label>Dacomitinib and Osimertinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Osimertinib</intervention_name>
    <description>Dose level 1, 2 and 3 Osimertinib 40mg daily. Three patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.</description>
    <arm_group_label>Dacomitinib and 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&#xD;
&#xD;
          -  No prior EGFR inhibitor treatment (gefitinib, afatinib, erlotinib, dacomitinib,&#xD;
             osimertinib) however, prior treatment with other chemotherapies are allowed&#xD;
&#xD;
          -  Archival tissue available from a pre-treatment tumor biopsy or willing to undergo a&#xD;
             tumor biopsy prior to study initiation.&#xD;
&#xD;
          -  Measurable (RECIST 1.1) indicator lesion not previously irradiated&#xD;
&#xD;
          -  Karnofsky performance status (KPS) ≥ 70%&#xD;
&#xD;
          -  Age &gt;18 years old&#xD;
&#xD;
          -  Ability to swallow oral medication&#xD;
&#xD;
          -  Agree to use effective methods of contraception from the time of screening until 3&#xD;
             months after treatment discontinuation (for males and females of child-bearing&#xD;
             potential)&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
               -  AST, ALT ≤ 3 x ULN&#xD;
&#xD;
               -  Total bilirubin ≤1.5x ULN&#xD;
&#xD;
               -  Creatinine ≤ 1.5x ULN OR calculated creatinine clearance ≥ 60ml/min&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1000 cells/mm^3&#xD;
&#xD;
               -  Hemoglobin≥9.0 g/dL&#xD;
&#xD;
               -  Platelets ≥100,000/mm^3&#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;
          -  A mean QTc &gt;470ms (Fridericia&quot;s correction), clinically important arrhythmia,&#xD;
             conduction or morphology of resting ECG (eg complete LBBB, 1st -3rd degree heart&#xD;
             block, any factors that increase the risk of QTc prolongation or risk of arrhythmia)&#xD;
&#xD;
          -  Cardiovascular disease or cerebrovascular disease, CVA or MI &lt; 6 months prior to study&#xD;
             enrollment, unstable angina, NYHA &gt;Grade II CHF, or serious cardiac arrhythmia&#xD;
             uncontrolled by medication or with the potential to interfere with protocol treatment&#xD;
&#xD;
          -  History of pneumonitis or interstitial lung disease (ILD), drug induced ILD, radiation&#xD;
             pneumonitits that required steroid treatment, and any evidence of clinically active&#xD;
             ILD&#xD;
&#xD;
          -  Serious chronic GI conditions associated with diarrhea&#xD;
&#xD;
          -  Symptomatic, unstable brain metastases requiring escalating doses of steroids&#xD;
&#xD;
          -  Continue to have unresolved &gt; CTCAE grade 1 toxicity from any previous treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Helena 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 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/mskcc/html/44.cfm</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>June 30, 2023</last_update_submitted>
  <last_update_submitted_qc>June 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dacomitinib</keyword>
  <keyword>Osimertinib</keyword>
  <keyword>EGFR Mutant Lung Cancers</keyword>
  <keyword>18-411</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>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
  </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/NCT03810807
org study id: 18-411
nct id: NCT03810807
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to test the safety of dacomitinib and osimertinib, at increasing
      doses, to find out what effects, if any, this combination of drugs has on people with
      metastatic EGFR mutant lung cancer that has not been treated with an EGFR TKI.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: maximum tolerated dose
time frame: 1 year
description: The MTD will be defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity (DLT). DLT is defined as any of the toxicity events described below that occurs within cycle 1 of treatment with the combination of dacomitinib and osimertinib.
measure: Best overall response rate
time frame: 1 year
description: Tumor response will be assessed using RECIST 1.1.The NCI Common Terminology Criteria for Adverse Events Version 5 (NCI-CTCAE) will be used to grade toxicities during the trial. Dose-limiting toxicities (DLT"s) are defined as any of the following events occurring during the first cycle of treatment
arm group label: Dacomitinib and Osimertinib
arm group type: Experimental
description: Patients will begin on combination dacomitinib and osimertinib at the prescribed doses.
A cycle will be 28 days in duration. The study will use a standard 3+3 dose escalation design. Per MD discretion, telemedicine visits may be utilized for cycles where imaging is not collected, and physical exam, vital sign and labs collection will only be required concurrent with imaging visits.
intervention type: Drug
intervention name: Dacomitinib
description: Dose level 1 Dacomitinib, Dose level 2 Dacomitinib, Dose level 3 Dacomitinib. Three patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.
arm group label: Dacomitinib and Osimertinib
intervention type: Drug
intervention name: Osimertinib
description: Dose level 1, 2 and 3 Osimertinib 40mg daily. Three patients will need to be enrolled at each dose level and assessed for DLT for 1 full cycle (28 days for cycle 1) before dose escalation decision is made.
arm group label: Dacomitinib and Osimertinib
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Helena Yu, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org/mskcc/html/44.cfm
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.
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)