<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/NCT02208843</url>
  </required_header>
  <id_info>
    <org_study_id>1200.217</org_study_id>
    <secondary_id>2014-001077-14</secondary_id>
    <nct_id>NCT02208843</nct_id>
  </id_info>
  <brief_title>Afatinib as Second-line Therapy for Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation</brief_title>
  <official_title>An Open Label, Single-arm Phase IV Study to Assess the Efficacy and Safety of Afatinib as Second-line Therapy for Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Harbouring an EGFR Mutation (Del19 or L858R) Who Have Failed First-line Treatment With Platinum-based Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      The objectives of this single-arm, open-label trial are to assess the efficacy and safety of&#xD;
      afatinib as second line treatment for patients with locally advanced or metastatic non-small&#xD;
      cell lung cancer (NSCLC) harbouring a common EGFR mutation who have failed first-line&#xD;
      platinum-based chemotherapy and to demonstrate that the efficacy and safety are comparable to&#xD;
      the results seen in previous trials.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2, 2014</start_date>
  <completion_date type="Actual">June 13, 2017</completion_date>
  <primary_completion_date type="Actual">May 17, 2017</primary_completion_date>
  <phase>Phase 4</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>Objective Tumour Response (Complete Response [CR], Partial Response [PR]) as Assessed by the Investigator According to the RECIST Version 1.1</measure>
    <time_frame>Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days</time_frame>
    <description>As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) as Assessed by the Investigator According to RECIST 1.1.</measure>
    <time_frame>Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days</time_frame>
    <description>Progression-free survival (PFS) is the time from treatment start to disease progression (or death if the patient died before progression). PFS as assessed based on investigator review according to the response evaluation criteria in solid tumours (RECIST) version 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control (CR, PR, Stable Disease [SD]) as Assessed by the Investigator According to RECIST 1.1</measure>
    <time_frame>Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days</time_frame>
    <description>As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Carcinoma, Non-Small-Cell Lung</condition>
  <arm_group>
    <arm_group_label>Afatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Afatinib tablet once daily until progression</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Afatinib</intervention_name>
    <description>Afatinib tablet once daily until progression</description>
    <arm_group_label>Afatinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Pathologically confirmed diagnosis of Stage IIIB (with cytologically proven pleural&#xD;
             effusion or pericardial effusion) or Stage IV adenocarcinoma of the lung. Patients&#xD;
             with mixed histology are eligible if adenocarcinoma is the predominant histology.&#xD;
&#xD;
          2. Documented EGFR mutation (L858R and/or Deletion 19) with no other known EGFR mutation.&#xD;
&#xD;
          3. Measureable disease according to RECIST 1.1.&#xD;
&#xD;
          4. Radiologically confirmed progression or recurrence of disease during or following&#xD;
             first line therapy with a platinum-based chemotherapy regimen.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.&#xD;
&#xD;
          6. Adequate organ function.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. More than one line of prior therapy for disease.&#xD;
&#xD;
          2. Previously received less than 3 cycles of platinum-based chemotherapy due to toxicity&#xD;
             and/or intolerance of treatment.&#xD;
&#xD;
          3. Previous treatment with any EGFR targeting Tyrosine Kinase Inhibitor (TKI) or&#xD;
             antibody.&#xD;
&#xD;
          4. Known pre-existing interstitial lung disease.&#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>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Research Center, Alexandria University Hospital</name>
      <address>
        <city>Alexandria</city>
        <zip>21131</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Institute, Cairo University</name>
      <address>
        <city>Cairo</city>
        <zip>11796</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kasr Al Ainy Hospital</name>
      <address>
        <city>Cairo</city>
        <zip>12311</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nilai Medical Centre</name>
      <address>
        <city>Nilai</city>
        <zip>71800</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baguio General Hospital and Medical Center</name>
      <address>
        <city>Baguio City</city>
        <zip>2600</zip>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's Medical Center</name>
      <address>
        <city>Taguig</city>
        <zip>1634</zip>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Clinical Center, Gdansk</name>
      <address>
        <city>Gdansk</city>
        <zip>80-952</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Specialist Hospital, Szczecin-Zdunowo</name>
      <address>
        <city>Szczecin-Zdunowo</city>
        <zip>70-891</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncol Centre M Sklodowska-Curie, Dept of Lung &amp; Chest Cancer</name>
      <address>
        <city>Warsaw</city>
        <zip>02-781</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Braila County Emergency Hospital, Medical Oncology</name>
      <address>
        <city>Braila</city>
        <zip>810303</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Oncology 'Prof. Dr. Alexandru Trestioreanu'</name>
      <address>
        <city>Bucharest</city>
        <zip>022328</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sf. Nectarie Oncology Center, Craiova</name>
      <address>
        <city>Craiova</city>
        <zip>200347</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Oncology Institute of Iasi, Medical Oncology</name>
      <address>
        <city>Iasi</city>
        <zip>700483</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute for Oncol &amp; Radiol of Serbia, Clinic f. Med. Onco.</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center of Serbia</name>
      <address>
        <city>Belgrade</city>
        <zip>11129</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center Kragujevac</name>
      <address>
        <city>Kragujevac</city>
        <zip>34000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inst. for Pulm. Diseases of Vojvodine, Clinic f. Pulm. Oncol</name>
      <address>
        <city>Sremska Kamenica</city>
        <zip>21204</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wattanosoth Hospital</name>
      <address>
        <city>Bangkok</city>
        <zip>10310</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King Chulalongkorn Memorial Hospital</name>
      <address>
        <city>Bangkok</city>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rajavithi Hospital</name>
      <address>
        <city>Bangkok</city>
        <zip>10400</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Songklanagarind Hospital</name>
      <address>
        <city>Songkhla</city>
        <zip>90110</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
    <country>Malaysia</country>
    <country>Philippines</country>
    <country>Poland</country>
    <country>Romania</country>
    <country>Serbia</country>
    <country>Thailand</country>
  </location_countries>
  <link>
    <url>http://trials.boehringer-ingelheim.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>June 2018</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 5, 2014</study_first_posted>
  <results_first_submitted>June 1, 2018</results_first_submitted>
  <results_first_submitted_qc>June 1, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">December 17, 2018</results_first_posted>
  <last_update_submitted>June 1, 2018</last_update_submitted>
  <last_update_submitted_qc>June 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 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>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Afatinib</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 10, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT02208843/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 22, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT02208843/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>An open-label, single-arm phase IV study to assess the efficacy and safety of Afatinib as second-line therapy for patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) harbouring an Epidermal Growth Factor Receptor(EGFR) mutation (Del19 or L858R) who have failed first-line treatment with platinum-based chemotherapy.</recruitment_details>
      <pre_assignment_details>All patients were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that all subjects met all inclusion/exclusion criteria. Subjects were not to be entered to trial treatment if any one of the specific entry criteria were not met.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Afatinib 40 mg</title>
          <description>All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="60"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="60"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Clinical symptoms of progression</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progression disease according to RECIST</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Switched to commercial afatinib</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.</population>
      <group_list>
        <group group_id="B1">
          <title>Afatinib 40 mg</title>
          <description>All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="60"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Age at the time of signing informed consent form is presented.</description>
          <population>Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.</population>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.9" spread="9.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>Number of subjects is categorized as Male or Female.</description>
          <population>Treated Set (TS): The TS included all patients who were documented to have taken at least 1 dose of afatinib.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <description>Number of subjects is categorized for race data. Ethnicity data were not collected for this study.</description>
          <population>Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <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="19"/>
                  </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="41"/>
                  </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>Objective Tumour Response (Complete Response [CR], Partial Response [PR]) as Assessed by the Investigator According to the RECIST Version 1.1</title>
        <description>As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions</description>
        <time_frame>Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days</time_frame>
        <population>Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.</population>
        <group_list>
          <group group_id="O1">
            <title>Afatinib 40 mg</title>
            <description>All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Tumour Response (Complete Response [CR], Partial Response [PR]) as Assessed by the Investigator According to the RECIST Version 1.1</title>
          <description>As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions</description>
          <population>Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.</population>
          <units>Percentage 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="60"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50" lower_limit="36.8" upper_limit="63.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS) as Assessed by the Investigator According to RECIST 1.1.</title>
        <description>Progression-free survival (PFS) is the time from treatment start to disease progression (or death if the patient died before progression). PFS as assessed based on investigator review according to the response evaluation criteria in solid tumours (RECIST) version 1.1.</description>
        <time_frame>Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days</time_frame>
        <population>Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.</population>
        <group_list>
          <group group_id="O1">
            <title>Afatinib 40 mg</title>
            <description>All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS) as Assessed by the Investigator According to RECIST 1.1.</title>
          <description>Progression-free survival (PFS) is the time from treatment start to disease progression (or death if the patient died before progression). PFS as assessed based on investigator review according to the response evaluation criteria in solid tumours (RECIST) version 1.1.</description>
          <population>Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.</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="60"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.94" lower_limit="6.44" upper_limit="13.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Control (CR, PR, Stable Disease [SD]) as Assessed by the Investigator According to RECIST 1.1</title>
        <description>As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.</description>
        <time_frame>Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days</time_frame>
        <population>Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.</population>
        <group_list>
          <group group_id="O1">
            <title>Afatinib 40 mg</title>
            <description>All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control (CR, PR, Stable Disease [SD]) as Assessed by the Investigator According to RECIST 1.1</title>
          <description>As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.</description>
          <population>Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.</population>
          <units>Percentage 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="60"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83.3" lower_limit="71.5" upper_limit="91.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first drug administration until 28 days after last drug administration, up to 830 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Afatinib 40 mg</title>
          <description>All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.0</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="11" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Malignant pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Brain oedema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hemiparesis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Nervous system disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Neurological decompensation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.0</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="56" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="44" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="60"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Nail pitting</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="60"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="60"/>
              </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>Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Boehringer Ingelheim, Call Centre</name_or_title>
      <organization>Boehringer Ingelheim</organization>
      <phone>1-800-243-0127</phone>
      <email>clintriage.rdg@boehringer-ingelheim.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/NCT02208843
org study id: 1200.217
secondary id: 2014-001077-14
nct id: NCT02208843
lead sponsor: 
The objectives of this single-arm, open-label trial are to assess the efficacy and safety of
      afatinib as second line treatment for patients with locally advanced or metastatic non-small
      cell lung cancer (NSCLC) harbouring a common EGFR mutation who have failed first-line
      platinum-based chemotherapy and to demonstrate that the efficacy and safety are comparable to
      the results seen in previous trials.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Tumour Response (Complete Response [CR], Partial Response [PR]) as Assessed by the Investigator According to the RECIST Version 1.1
time frame: Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days
description: As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions
measure: Progression-free Survival (PFS) as Assessed by the Investigator According to RECIST 1.1.
time frame: Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days
description: Progression-free survival (PFS) is the time from treatment start to disease progression (or death if the patient died before progression). PFS as assessed based on investigator review according to the response evaluation criteria in solid tumours (RECIST) version 1.1.
measure: Disease Control (CR, PR, Stable Disease [SD]) as Assessed by the Investigator According to RECIST 1.1
time frame: Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days
description: As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
arm group label: Afatinib
arm group type: Experimental
description: Afatinib tablet once daily until progression
intervention type: Drug
intervention name: Afatinib
description: Afatinib tablet once daily until progression
arm group label: Afatinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
facility: 
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country: Egypt
country: Malaysia
country: Philippines
country: Poland
country: Romania
country: Serbia
country: Thailand
url: http://trials.boehringer-ingelheim.com/
description: Related Info
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Afatinib
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 