<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/NCT01667562</url>
  </required_header>
  <id_info>
    <org_study_id>ML27860</org_study_id>
    <nct_id>NCT01667562</nct_id>
  </id_info>
  <brief_title>A Study of Erlotinib in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer</brief_title>
  <acronym>ESSENCE</acronym>
  <official_title>Phase IIIb, Open-Label Study of Erlotinib (Tarceva®) Treatment in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Present Activating Mutations in the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <brief_summary>
    <textblock>
      This open-label, multi-center study will evaluate the progression-free survival and safety of&#xD;
      erlotinib in participants with locally advanced or metastatic non-small cell lung cancer with&#xD;
      activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor&#xD;
      (EGFR). Participants will receive daily oral doses of erlotinib until disease progression or&#xD;
      unacceptable toxicity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 20, 2012</start_date>
  <completion_date type="Actual">September 7, 2017</completion_date>
  <primary_completion_date type="Actual">September 7, 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-Free Survival as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v 1.1)</measure>
    <time_frame>Baseline until disease progression, or death, whichever occurs first (approximately up to 4 years and 9 months)</time_frame>
    <description>Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Patients who had not died or progressed at the time of the final analysis were censored at the date of last contact.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants With Objective Response as Assessed by RECIST v 1.1</measure>
    <time_frame>Baseline until disease progression, or death, whichever occurs first (approximately up to 4 years and 9 months)</time_frame>
    <description>Objective response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR) four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants With Disease Control as Assessed by RECIST v 1.1</measure>
    <time_frame>Baseline until disease progression, or death, whichever occurs first (approximately up to 4 years and 9 months)</time_frame>
    <description>Disease control was defined as objective response or stable disease (SD) for at least 6 weeks. OR was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of CR and PR four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations</measure>
    <time_frame>Screening up to approximately 7 days</time_frame>
    <description>Mutations in the EGFR included exon 19 deletion mutations and the single-point substitution mutation L858R in exon 21.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adverse Events</measure>
    <time_frame>Baseline up to approximately 4 years and 9 months</time_frame>
    <description>An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to End of Study in Quality of Life Score Using The Functional Assessment of Cancer Therapy Lung (FACT-L)</measure>
    <time_frame>Baseline and end of study (approximately 4 years and 9 months)</time_frame>
    <description>The domains in the Quality of life score using the Functional Assessment of Cancer Therapy Lung (FACT-L) include physical, social/family, emotional, and functional well-being, and a lung cancer subscale include symptoms, cognitive function and regret of smoking. Minimum and maximum value of the scale is 0 and 4, respectively. Higher score indicate better health state.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">375</enrollment>
  <condition>Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Erlotinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Erlotinib will be administered as a single daily oral dose of 150 milligrams until disease progression, death or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diagnostic Phase</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants with advanced or metastatic NSCLC were tested for EGFR mutations. Participants who did not have an EGFR mutation were excluded from the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Erlotinib</intervention_name>
    <description>Daily oral doses administered until disease progression or unacceptable toxicity or death.</description>
    <arm_group_label>Erlotinib</arm_group_label>
    <other_name>Tarceva</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of locally advanced or metastatic non-small cell lung cancer with activating&#xD;
             mutations in the tyrosine kinase domain of the EGFR&#xD;
&#xD;
          -  Measurable disease according to RECIST&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2&#xD;
&#xD;
          -  Life expectancy greater than or equal to (&gt;/=) 12 weeks&#xD;
&#xD;
          -  Adequate hematological, liver and renal function&#xD;
&#xD;
          -  Participants with asymptomatic and stable cerebral metastases receiving medical&#xD;
             treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous chemotherapy or treatment against EGFR for metastatic disease&#xD;
&#xD;
          -  Treatment with an investigational agent less than 3 weeks before enrollment&#xD;
&#xD;
          -  History of neoplasm other than non-small cell lung cancer (except carcinoma in situ of&#xD;
             the uterine cervix, basal cell skin carcinoma, or prostate carcinoma)&#xD;
&#xD;
          -  Participants with symptomatic cerebral metastases&#xD;
&#xD;
          -  Any significant ophthalmologic abnormality&#xD;
&#xD;
          -  Unstable systemic disease&#xD;
&#xD;
          -  Coumarins use&#xD;
&#xD;
          -  Evidence of any other disease, neurological or metabolic dysfunction, physical&#xD;
             examination or laboratory finding contraindicating the use of an investigational drug&#xD;
&#xD;
          -  Participants with pre-existing parenchymal lung disease such as pulmonary fibrosis,&#xD;
             lymphangiosis carcinomatosis&#xD;
&#xD;
          -  Participants with known infection with human immunodeficiency virus (HIV), Hepatitis B&#xD;
             (HBV), Hepatitis C (HCV)&#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>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinic for Pulmonology, Clinical Center of Serbia</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center Bezanijska Kosa; Oncology</name>
      <address>
        <city>Belgrade</city>
        <zip>11080</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center Nis; Clinic for pulmonary diseases Knez Selo</name>
      <address>
        <city>Nis</city>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute for pulmonary diseases of Vojvodina</name>
      <address>
        <city>Sremska Kamenica</city>
        <zip>21204</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Serbia</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>August 15, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <results_first_submitted>August 23, 2018</results_first_submitted>
  <results_first_submitted_qc>December 2, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">December 20, 2019</results_first_posted>
  <last_update_submitted>December 2, 2019</last_update_submitted>
  <last_update_submitted_qc>December 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 20, 2019</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>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Erlotinib Hydrochloride</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 16, 2012</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/62/NCT01667562/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>375 participants were in the diagnostic population. Out of the 375 participants, only 30 participants had EGFR mutation and were eligible for erlotinib treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Diagnostic Phase</title>
          <description>Participants with advanced or metastatic NSCLC were tested for EGFR mutations. Participants who did not have an EGFR mutation were excluded from the study.</description>
        </group>
        <group group_id="P2">
          <title>Erlotinib</title>
          <description>Erlotinib was administered as a single daily oral dose of 150 milligrams until disease progression, death or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Diagnostic Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="375"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="345"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Started Erlotinib in Treatment Period</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Erlotinib Phase</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Switch to Commercial Drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The intent-to-treat (ITT) population included all participants enrolled in the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Baseline Population</title>
          <description>Participants with advanced or metastatic NSCLC were tested for EGFR mutations and enrolled in the study.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="375"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>375 participants were in the diagnostic population. Out of the 375 participants, only 30 participants had EGFR mutation and were eligible for erlotinib treatment.</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Diagnostic Phase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="375"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.2" spread="9.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erlotinib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.4" spread="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>375 participants were in the diagnostic population. Out of the 375 participants, only 30 participants had EGFR mutation and were eligible for erlotinib treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Diagnostic Phase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="375"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="133"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="242"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erlotinib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>375 participants were in the diagnostic population. Out of the 375 participants, only 30 participants had EGFR mutation and were eligible for erlotinib treatment.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Diagnostic Phase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="375"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="375"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erlotinib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="30"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression-Free Survival as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v 1.1)</title>
        <description>Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Patients who had not died or progressed at the time of the final analysis were censored at the date of last contact.</description>
        <time_frame>Baseline until disease progression, or death, whichever occurs first (approximately up to 4 years and 9 months)</time_frame>
        <population>The intent-to-treat population included all participants enrolled in the study. There were no patients excluded from analysis either in efficacy and safety analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Erlotinib</title>
            <description>Erlotinib was administered as a single daily oral dose of 150 milligrams until disease progression, death or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-Free Survival as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v 1.1)</title>
          <description>Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Patients who had not died or progressed at the time of the final analysis were censored at the date of last contact.</description>
          <population>The intent-to-treat population included all participants enrolled in the study. There were no patients excluded from analysis either in efficacy and safety analysis.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.574" lower_limit="5.525" upper_limit="13.662"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Participants With Objective Response as Assessed by RECIST v 1.1</title>
        <description>Objective response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR) four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.</description>
        <time_frame>Baseline until disease progression, or death, whichever occurs first (approximately up to 4 years and 9 months)</time_frame>
        <population>The intent-to-treat population included all participants enrolled in the study. There were no patients excluded from analysis either in efficacy and safety analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Erlotinib</title>
            <description>Erlotinib was administered as a single daily oral dose of 150 milligrams until disease progression, death or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With Objective Response as Assessed by RECIST v 1.1</title>
          <description>Objective response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR) four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.</description>
          <population>The intent-to-treat population included all participants enrolled in the study. There were no patients excluded from analysis either in efficacy and safety analysis.</population>
          <units>proportion of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.67" lower_limit="0.49" upper_limit="0.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Participants With Disease Control as Assessed by RECIST v 1.1</title>
        <description>Disease control was defined as objective response or stable disease (SD) for at least 6 weeks. OR was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of CR and PR four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.</description>
        <time_frame>Baseline until disease progression, or death, whichever occurs first (approximately up to 4 years and 9 months)</time_frame>
        <population>The intent-to-treat population included all participants enrolled in the study. There were no patients excluded from analysis either in efficacy and safety analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Erlotinib</title>
            <description>Erlotinib was administered as a single daily oral dose of 150 milligrams until disease progression, death or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With Disease Control as Assessed by RECIST v 1.1</title>
          <description>Disease control was defined as objective response or stable disease (SD) for at least 6 weeks. OR was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of CR and PR four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.</description>
          <population>The intent-to-treat population included all participants enrolled in the study. There were no patients excluded from analysis either in efficacy and safety analysis.</population>
          <units>proportion of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.97" lower_limit="0.82" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations</title>
        <description>Mutations in the EGFR included exon 19 deletion mutations and the single-point substitution mutation L858R in exon 21.</description>
        <time_frame>Screening up to approximately 7 days</time_frame>
        <population>This study had 2 phases: 1st phase - included 375 patients assessed for EGFR mutations 30 patients (out of these 375) had EGFR mutations and they were included in 2nd phase - treatment with Erlotinib.</population>
        <group_list>
          <group group_id="O1">
            <title>Diagnostic Phase</title>
            <description>Participants with advanced or metastatic NSCLC were tested for EGFR mutations. Participants who did not have an EGFR mutation were excluded from the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations</title>
          <description>Mutations in the EGFR included exon 19 deletion mutations and the single-point substitution mutation L858R in exon 21.</description>
          <population>This study had 2 phases: 1st phase - included 375 patients assessed for EGFR mutations 30 patients (out of these 375) had EGFR mutations and they were included in 2nd phase - treatment with Erlotinib.</population>
          <units>proportion of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="375"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.08" lower_limit="0.06" upper_limit="0.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Adverse Events</title>
        <description>An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
        <time_frame>Baseline up to approximately 4 years and 9 months</time_frame>
        <population>The safety population was identical to the ITT population, which included all participants enrolled in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Erlotinib</title>
            <description>Erlotinib was administered as a single daily oral dose of 150 milligrams until disease progression, death or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Adverse Events</title>
          <description>An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
          <population>The safety population was identical to the ITT population, which included all participants enrolled in the study.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to End of Study in Quality of Life Score Using The Functional Assessment of Cancer Therapy Lung (FACT-L)</title>
        <description>The domains in the Quality of life score using the Functional Assessment of Cancer Therapy Lung (FACT-L) include physical, social/family, emotional, and functional well-being, and a lung cancer subscale include symptoms, cognitive function and regret of smoking. Minimum and maximum value of the scale is 0 and 4, respectively. Higher score indicate better health state.</description>
        <time_frame>Baseline and end of study (approximately 4 years and 9 months)</time_frame>
        <population>Participants without disease progression who filled out the FACT-L questionnaire.</population>
        <group_list>
          <group group_id="O1">
            <title>Erlotinib</title>
            <description>Erlotinib was administered as a single daily oral dose of 150 milligrams until disease progression, death or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to End of Study in Quality of Life Score Using The Functional Assessment of Cancer Therapy Lung (FACT-L)</title>
          <description>The domains in the Quality of life score using the Functional Assessment of Cancer Therapy Lung (FACT-L) include physical, social/family, emotional, and functional well-being, and a lung cancer subscale include symptoms, cognitive function and regret of smoking. Minimum and maximum value of the scale is 0 and 4, respectively. Higher score indicate better health state.</description>
          <population>Participants without disease progression who filled out the FACT-L questionnaire.</population>
          <units>unit on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.83" spread="NA">The standard deviation could not be calculated for one participant who had data for this outcome.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>4 years and 9 months</time_frame>
      <desc>The safety population was identical to the ITT population. The ITT population comprised all 30 patients.</desc>
      <group_list>
        <group group_id="E1">
          <title>Erlotinib</title>
          <description>Erlotinib was administered as a single daily oral dose of 150 milligrams until disease progression, death or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA, version 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA, version 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-La Roche</organization>
      <phone>800 821-8590</phone>
      <email>genentech@druginfo.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01667562
org study id: ML27860
nct id: NCT01667562
lead sponsor: 
This open-label, multi-center study will evaluate the progression-free survival and safety of
      erlotinib in participants with locally advanced or metastatic non-small cell lung cancer with
      activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor
      (EGFR). Participants will receive daily oral doses of erlotinib until disease progression or
      unacceptable toxicity.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-Free Survival as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v 1.1)
time frame: Baseline until disease progression, or death, whichever occurs first (approximately up to 4 years and 9 months)
description: Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]) based on RECIST tumor response criteria or died from any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Patients who had not died or progressed at the time of the final analysis were censored at the date of last contact.
measure: Proportion of Participants With Objective Response as Assessed by RECIST v 1.1
time frame: Baseline until disease progression, or death, whichever occurs first (approximately up to 4 years and 9 months)
description: Objective response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR) four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
measure: Proportion of Participants With Disease Control as Assessed by RECIST v 1.1
time frame: Baseline until disease progression, or death, whichever occurs first (approximately up to 4 years and 9 months)
description: Disease control was defined as objective response or stable disease (SD) for at least 6 weeks. OR was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of CR and PR four at least 4 weeks during treatment. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
measure: Proportion of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations
time frame: Screening up to approximately 7 days
description: Mutations in the EGFR included exon 19 deletion mutations and the single-point substitution mutation L858R in exon 21.
measure: Percentage of Participants With Adverse Events
time frame: Baseline up to approximately 4 years and 9 months
description: An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
measure: Change From Baseline to End of Study in Quality of Life Score Using The Functional Assessment of Cancer Therapy Lung (FACT-L)
time frame: Baseline and end of study (approximately 4 years and 9 months)
description: The domains in the Quality of life score using the Functional Assessment of Cancer Therapy Lung (FACT-L) include physical, social/family, emotional, and functional well-being, and a lung cancer subscale include symptoms, cognitive function and regret of smoking. Minimum and maximum value of the scale is 0 and 4, respectively. Higher score indicate better health state.
arm group label: Erlotinib
arm group type: Experimental
description: Erlotinib will be administered as a single daily oral dose of 150 milligrams until disease progression, death or unacceptable toxicity.
arm group label: Diagnostic Phase
arm group type: No Intervention
description: Participants with advanced or metastatic NSCLC were tested for EGFR mutations. Participants who did not have an EGFR mutation were excluded from the study.
intervention type: Drug
intervention name: Erlotinib
description: Daily oral doses administered until disease progression or unacceptable toxicity or death.
arm group label: Erlotinib
other name: Tarceva
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
facility: 
facility: 
country: Serbia
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Erlotinib Hydrochloride
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 