<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/NCT01728623</url>
  </required_header>
  <id_info>
    <org_study_id>E7080-J081-208</org_study_id>
    <nct_id>NCT01728623</nct_id>
  </id_info>
  <brief_title>A Study of E7080 in Subjects With Advanced Thyroid Cancer</brief_title>
  <official_title>A Phase 2 Study of E7080 in Subjects With Advanced Thyroid Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eisai Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eisai Inc.</source>
  <brief_summary>
    <textblock>
      This study is to evaluate the safety, efficacy, and pharmacokinetics of E7080 when orally&#xD;
      administered once daily (QD) in subjects with advanced thyroid cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 3, 2012</start_date>
  <completion_date type="Actual">October 1, 2015</completion_date>
  <primary_completion_date type="Actual">July 9, 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>Screening visit to 30 days after the last dose of study drug, or assessed up to 3 years</time_frame>
    <description>Only TEAEs are included in the summary. For detailed list of adverse events (AEs), see the AE section. For each participant, only one TEAE in the same category was counted and for multiple TEAEs with different Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.0) grades, only the event with the highest grade was reported. All AEs were graded using CTCAE v 4.0, except for alopecia and infertility.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>From first date of study treatment until progression of disease or date of death from any cause, whichever comes first, assessed up to 34 months</time_frame>
    <description>PFS was defined as the time from (1) the date of randomization to the date of first documentation of disease progression based on Investigator and Independent Review Committee assessments according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), or (2) death, whichever came first. Disease progression for the MTC group was measured using computed tomography (CT) or magnetic resonance imaging (MRI) on targeted tumors. Disease progression per RECIST v1.1 was defined as at least a 20 percent (%) relative increase and 5 millimeter (mm) absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions. Summarized by the Kaplan-Meier method using median time with 95% confidence interval (CI).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From study start until date of death from any cause, assessed up to 34 months</time_frame>
    <description>OS was defined as the time from the date of first dose of study treatment to the date of death from any cause. If death was not observed for a participant, the survival time was censored at the date the participant was last known alive or the data cutoff date (whichever occurred first). Summarized by the Kaplan-Meier method using median time with 95% CI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response (BOR)</measure>
    <time_frame>Date of first dose of study treatment to CR, PR, SD, PD, or NE, assessed up to 34 months</time_frame>
    <description>BOR was defined as the best response observed between the time of first dose and the study completion, assessed by either of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE). Tumor assessment was performed by the investigator using RECIST 1.1. The CR and PR were determined only when these responses met each criterion even after 28 days from the time observed. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as greater than or equal to 7 weeks for DTC and MTC, greater than or equal to 3 weeks for ATC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Date of CR or PR to date of PD or death (whichever was first), assessed up to 34 months</time_frame>
    <description>ORR was defined as the percentage of participants who had BOR of CR or PR. Tumor assessment was performed by the investigator using RECIST 1.1. ORR based on the investigator assessment was provided with a corresponding exact 95% CI which was calculated using exact method of binomial distribution.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Date of CR, PR, or SD to date of PD or death (whichever was first), assessed up to 34 months</time_frame>
    <description>The DCR was defined as the percentage of participants who had BOR of CR, PR, or SD. Tumor assessment was performed by the investigator using RECIST 1.1. DCR based on the investigator assessment was provided with a corresponding exact 95% CI which was calculated using exact method of binomial distribution.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate (CBR)</measure>
    <time_frame>Date of CR, PR, or dSD to date of PD or death (whichever was first), assessed up to 34 months</time_frame>
    <description>The CBR was defined as the percentage of participants who had BOR of CR, PR, or durable SD (dSD). Tumor assessment was performed by the investigator using RECIST 1.1. Durable stable disease was defined as SD lasting greater than or equal to 23 weeks for DTC and MTC, greater than or equal to 11 weeks for ATC. A 95% CI was calculated using exact method of binomial distribution.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>Thyroid Cancer</condition>
  <arm_group>
    <arm_group_label>E7080</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>E7080 capsule</intervention_name>
    <description>E7080 is administered as continuous once daily dosing in an uncontrolled manner</description>
    <arm_group_label>E7080</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          1. Histologically or clinically diagnosed with thyroid cancer&#xD;
&#xD;
          2. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0-2&#xD;
&#xD;
          3. Adequate laboratory values/organ function tests&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
        Participants with following complication or disease history&#xD;
&#xD;
          1. Brain metastasis&#xD;
&#xD;
          2. Systemic severe infection&#xD;
&#xD;
          3. Significant cardiovascular impairment&#xD;
&#xD;
          4. QTc greater than 480 milliseconds&#xD;
&#xD;
          5. Active hemoptysis&#xD;
&#xD;
          6. Bleeding or thrombotic disorders&#xD;
&#xD;
          7. Having greater than 1+ proteinuria on urine dipstick testing will undergo 24 hour&#xD;
             urine collection for quantitative assessment of proteinuria&#xD;
&#xD;
          8. Gastrointestinal malabsorption or any other condition in the opinion of the&#xD;
             investigator that might affect the absorption of E7080&#xD;
&#xD;
          9. Major surgery within 3 weeks before enrollment&#xD;
&#xD;
         10. With co-existing effusion requiring drainage&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kobe</city>
        <state>Hyogo</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Koto-ward</city>
        <state>Tokyo</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>September 7, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <results_first_submitted>July 21, 2020</results_first_submitted>
  <results_first_submitted_qc>July 21, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 14, 2020</results_first_posted>
  <last_update_submitted>July 21, 2020</last_update_submitted>
  <last_update_submitted_qc>July 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Thyroid cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thyroid Neoplasms</mesh_term>
    <mesh_term>Thyroid Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lenvatinib</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm 4: Lenvatinib (MTC, DTC, ATC)</title>
          <description>Participants received 24 milligram (mg) lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 4 included all treated participants (differentiated thyroid cancer [DTC], medullary thyroid cancer [MTC], and anaplastic thyroid cancer [ATC]).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>DTC</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>MTC</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>ATC</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</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_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety analysis set included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation.</population>
      <group_list>
        <group group_id="B1">
          <title>Lenvatinib (Arm 1)</title>
          <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 1 included participants with DTC.</description>
        </group>
        <group group_id="B2">
          <title>Lenvatinib (Arm 2)</title>
          <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 2 included participants with MTC.</description>
        </group>
        <group group_id="B3">
          <title>Lenvatinib (Arm 3)</title>
          <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 3 included participants with ATC.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="17"/>
            <count group_id="B4" value="51"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57.1" spread="12.34"/>
                    <measurement group_id="B2" value="60.6" spread="13.70"/>
                    <measurement group_id="B3" value="63.4" spread="11.40"/>
                    <measurement group_id="B4" value="59.8" spread="12.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
        <description>Only TEAEs are included in the summary. For detailed list of adverse events (AEs), see the AE section. For each participant, only one TEAE in the same category was counted and for multiple TEAEs with different Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.0) grades, only the event with the highest grade was reported. All AEs were graded using CTCAE v 4.0, except for alopecia and infertility.</description>
        <time_frame>Screening visit to 30 days after the last dose of study drug, or assessed up to 3 years</time_frame>
        <population>Safety population included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm 4: Lenvatinib (DTC, MTC, ATC)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 4 included all treated participants (DTC, MTC and ATC).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
          <description>Only TEAEs are included in the summary. For detailed list of adverse events (AEs), see the AE section. For each participant, only one TEAE in the same category was counted and for multiple TEAEs with different Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.0) grades, only the event with the highest grade was reported. All AEs were graded using CTCAE v 4.0, except for alopecia and infertility.</description>
          <population>Safety population included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation.</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="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CTCAE Grade 3 or 4 TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs leading to study drug withdrawal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs leading to study drug reduction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="96.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs leading to study drug interruption</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>PFS was defined as the time from (1) the date of randomization to the date of first documentation of disease progression based on Investigator and Independent Review Committee assessments according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), or (2) death, whichever came first. Disease progression for the MTC group was measured using computed tomography (CT) or magnetic resonance imaging (MRI) on targeted tumors. Disease progression per RECIST v1.1 was defined as at least a 20 percent (%) relative increase and 5 millimeter (mm) absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions. Summarized by the Kaplan-Meier method using median time with 95% confidence interval (CI).</description>
        <time_frame>From first date of study treatment until progression of disease or date of death from any cause, whichever comes first, assessed up to 34 months</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib (Arm 1)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 1 included participants with DTC.</description>
          </group>
          <group group_id="O2">
            <title>Lenvatinib (Arm 2)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 2 included participants with MTC.</description>
          </group>
          <group group_id="O3">
            <title>Lenvatinib (Arm 3)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 3 included participants with ATC.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>PFS was defined as the time from (1) the date of randomization to the date of first documentation of disease progression based on Investigator and Independent Review Committee assessments according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), or (2) death, whichever came first. Disease progression for the MTC group was measured using computed tomography (CT) or magnetic resonance imaging (MRI) on targeted tumors. Disease progression per RECIST v1.1 was defined as at least a 20 percent (%) relative increase and 5 millimeter (mm) absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions. Summarized by the Kaplan-Meier method using median time with 95% confidence interval (CI).</description>
          <population>Full analysis set included all participants who received at least one dose of study drug.</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="25"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.8" lower_limit="18.4" upper_limit="NA">Upper limit of 95% confidence interval (CI) could not be calculated since insufficient number of participants had an event.</measurement>
                    <measurement group_id="O2" value="9.2" lower_limit="1.8" upper_limit="NA">Upper limit of 95% confidence interval (CI) could not be calculated since insufficient number of participants had an event.</measurement>
                    <measurement group_id="O3" value="7.4" lower_limit="1.7" upper_limit="12.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>OS was defined as the time from the date of first dose of study treatment to the date of death from any cause. If death was not observed for a participant, the survival time was censored at the date the participant was last known alive or the data cutoff date (whichever occurred first). Summarized by the Kaplan-Meier method using median time with 95% CI.</description>
        <time_frame>From study start until date of death from any cause, assessed up to 34 months</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib (Arm 1)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 1 included participants with DTC.</description>
          </group>
          <group group_id="O2">
            <title>Lenvatinib (Arm 2)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 2 included participants with MTC.</description>
          </group>
          <group group_id="O3">
            <title>Lenvatinib (Arm 3)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 3 included participants with ATC.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS was defined as the time from the date of first dose of study treatment to the date of death from any cause. If death was not observed for a participant, the survival time was censored at the date the participant was last known alive or the data cutoff date (whichever occurred first). Summarized by the Kaplan-Meier method using median time with 95% CI.</description>
          <population>Full analysis set included all participants who received at least one dose of study drug.</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="25"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.8" lower_limit="31.8" upper_limit="NA">Upper limit of 95% CI could not be calculated since insufficient number of participants had an event.</measurement>
                    <measurement group_id="O2" value="12.1" lower_limit="3.8" upper_limit="NA">Upper limit of 95% CI could not be calculated since insufficient number of participants had an event.</measurement>
                    <measurement group_id="O3" value="10.6" lower_limit="3.8" upper_limit="19.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Best Overall Response (BOR)</title>
        <description>BOR was defined as the best response observed between the time of first dose and the study completion, assessed by either of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE). Tumor assessment was performed by the investigator using RECIST 1.1. The CR and PR were determined only when these responses met each criterion even after 28 days from the time observed. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as greater than or equal to 7 weeks for DTC and MTC, greater than or equal to 3 weeks for ATC.</description>
        <time_frame>Date of first dose of study treatment to CR, PR, SD, PD, or NE, assessed up to 34 months</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib (Arm 1)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 1 included participants with DTC.</description>
          </group>
          <group group_id="O2">
            <title>Lenvatinib (Arm 2)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 2 included participants with MTC.</description>
          </group>
          <group group_id="O3">
            <title>Lenvatinib (Arm 3)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 3 included participants with ATC.</description>
          </group>
        </group_list>
        <measure>
          <title>Best Overall Response (BOR)</title>
          <description>BOR was defined as the best response observed between the time of first dose and the study completion, assessed by either of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE). Tumor assessment was performed by the investigator using RECIST 1.1. The CR and PR were determined only when these responses met each criterion even after 28 days from the time observed. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as greater than or equal to 7 weeks for DTC and MTC, greater than or equal to 3 weeks for ATC.</description>
          <population>Full analysis set included all participants who received at least one dose of study drug.</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="25"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.0"/>
                    <measurement group_id="O2" value="22.2"/>
                    <measurement group_id="O3" value="23.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.0"/>
                    <measurement group_id="O2" value="77.8"/>
                    <measurement group_id="O3" value="70.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>NE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR)</title>
        <description>ORR was defined as the percentage of participants who had BOR of CR or PR. Tumor assessment was performed by the investigator using RECIST 1.1. ORR based on the investigator assessment was provided with a corresponding exact 95% CI which was calculated using exact method of binomial distribution.</description>
        <time_frame>Date of CR or PR to date of PD or death (whichever was first), assessed up to 34 months</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib (Arm 1)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 1 included participants with DTC.</description>
          </group>
          <group group_id="O2">
            <title>Lenvatinib (Arm 2)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 2 included participants with MTC.</description>
          </group>
          <group group_id="O3">
            <title>Lenvatinib (Arm 3)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 3 included participants with ATC.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR)</title>
          <description>ORR was defined as the percentage of participants who had BOR of CR or PR. Tumor assessment was performed by the investigator using RECIST 1.1. ORR based on the investigator assessment was provided with a corresponding exact 95% CI which was calculated using exact method of binomial distribution.</description>
          <population>Full analysis set included all participants who received at least one dose of study drug.</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="25"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.0" lower_limit="46.5" upper_limit="85.1"/>
                    <measurement group_id="O2" value="22.2" lower_limit="2.8" upper_limit="60.0"/>
                    <measurement group_id="O3" value="23.5" lower_limit="6.8" upper_limit="49.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Control Rate (DCR)</title>
        <description>The DCR was defined as the percentage of participants who had BOR of CR, PR, or SD. Tumor assessment was performed by the investigator using RECIST 1.1. DCR based on the investigator assessment was provided with a corresponding exact 95% CI which was calculated using exact method of binomial distribution.</description>
        <time_frame>Date of CR, PR, or SD to date of PD or death (whichever was first), assessed up to 34 months</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib (Arm 1)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 1 included participants with DTC.</description>
          </group>
          <group group_id="O2">
            <title>Lenvatinib (Arm 2)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 2 included participants with MTC.</description>
          </group>
          <group group_id="O3">
            <title>Lenvatinib (Arm 3)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 3 included participants with ATC.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate (DCR)</title>
          <description>The DCR was defined as the percentage of participants who had BOR of CR, PR, or SD. Tumor assessment was performed by the investigator using RECIST 1.1. DCR based on the investigator assessment was provided with a corresponding exact 95% CI which was calculated using exact method of binomial distribution.</description>
          <population>Full analysis set included all participants who received at least one dose of study drug.</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="25"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100.0" lower_limit="86.3" upper_limit="100.0"/>
                    <measurement group_id="O2" value="100.0" lower_limit="66.4" upper_limit="100.0"/>
                    <measurement group_id="O3" value="94.1" lower_limit="71.3" upper_limit="99.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Rate (CBR)</title>
        <description>The CBR was defined as the percentage of participants who had BOR of CR, PR, or durable SD (dSD). Tumor assessment was performed by the investigator using RECIST 1.1. Durable stable disease was defined as SD lasting greater than or equal to 23 weeks for DTC and MTC, greater than or equal to 11 weeks for ATC. A 95% CI was calculated using exact method of binomial distribution.</description>
        <time_frame>Date of CR, PR, or dSD to date of PD or death (whichever was first), assessed up to 34 months</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib (Arm 1)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 1 included participants with DTC.</description>
          </group>
          <group group_id="O2">
            <title>Lenvatinib (Arm 2)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 2 included participants with MTC.</description>
          </group>
          <group group_id="O3">
            <title>Lenvatinib (Arm 3)</title>
            <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 3 included participants with ATC.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate (CBR)</title>
          <description>The CBR was defined as the percentage of participants who had BOR of CR, PR, or durable SD (dSD). Tumor assessment was performed by the investigator using RECIST 1.1. Durable stable disease was defined as SD lasting greater than or equal to 23 weeks for DTC and MTC, greater than or equal to 11 weeks for ATC. A 95% CI was calculated using exact method of binomial distribution.</description>
          <population>Full analysis set included all participants who received at least one dose of study drug.</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="25"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.0" lower_limit="63.9" upper_limit="95.5"/>
                    <measurement group_id="O2" value="77.8" lower_limit="40.0" upper_limit="97.2"/>
                    <measurement group_id="O3" value="70.6" lower_limit="44.0" upper_limit="89.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs were collected for up to 3 years</time_frame>
      <desc>Safety population included all participants who received at least one dose of study drug and had at least one postbaseline safety evaluation.</desc>
      <group_list>
        <group group_id="E1">
          <title>Arm 4: Lenvatinib (DTC, MTC, ATC)</title>
          <description>Participants received 24 mg lenvatinib capsule (two 10 mg capsules and one 4 mg capsule) orally once daily in the morning in a 28-day treatment cycle for until participant met one or more discontinuation criteria by individual participant. Arm 4 included all treated participants (DTC, MTC and ATC).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 18.0</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="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Haemorrhoidal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Upper limb fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </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="7" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Gastric cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Malignant pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Vagus nerve disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Vocal cord paralysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicide attempt</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Laryngeal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Tracheal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 18.0</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="51" subjects_at_risk="51"/>
              </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="5" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distention</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Cheilitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="37" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Contrast media allergy</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Gingivitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </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="39" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="51"/>
              </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="8" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="51"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="46" subjects_at_risk="51"/>
              </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>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Inquiry Service</name_or_title>
      <organization>Eisai Inc.</organization>
      <email>eisai-chiken_hotline@hhc.eisai.co.jp</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/NCT01728623
org study id: E7080-J081-208
nct id: NCT01728623
lead sponsor: 
This study is to evaluate the safety, efficacy, and pharmacokinetics of E7080 when orally
      administered once daily (QD) in subjects with advanced thyroid cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
time frame: Screening visit to 30 days after the last dose of study drug, or assessed up to 3 years
description: Only TEAEs are included in the summary. For detailed list of adverse events (AEs), see the AE section. For each participant, only one TEAE in the same category was counted and for multiple TEAEs with different Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4.0) grades, only the event with the highest grade was reported. All AEs were graded using CTCAE v 4.0, except for alopecia and infertility.
measure: Progression-free Survival (PFS)
time frame: From first date of study treatment until progression of disease or date of death from any cause, whichever comes first, assessed up to 34 months
description: PFS was defined as the time from (1) the date of randomization to the date of first documentation of disease progression based on Investigator and Independent Review Committee assessments according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), or (2) death, whichever came first. Disease progression for the MTC group was measured using computed tomography (CT) or magnetic resonance imaging (MRI) on targeted tumors. Disease progression per RECIST v1.1 was defined as at least a 20 percent (%) relative increase and 5 millimeter (mm) absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions. Summarized by the Kaplan-Meier method using median time with 95% confidence interval (CI).
measure: Overall Survival (OS)
time frame: From study start until date of death from any cause, assessed up to 34 months
description: OS was defined as the time from the date of first dose of study treatment to the date of death from any cause. If death was not observed for a participant, the survival time was censored at the date the participant was last known alive or the data cutoff date (whichever occurred first). Summarized by the Kaplan-Meier method using median time with 95% CI.
measure: Best Overall Response (BOR)
time frame: Date of first dose of study treatment to CR, PR, SD, PD, or NE, assessed up to 34 months
description: BOR was defined as the best response observed between the time of first dose and the study completion, assessed by either of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE). Tumor assessment was performed by the investigator using RECIST 1.1. The CR and PR were determined only when these responses met each criterion even after 28 days from the time observed. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as greater than or equal to 7 weeks for DTC and MTC, greater than or equal to 3 weeks for ATC.
measure: Objective Response Rate (ORR)
time frame: Date of CR or PR to date of PD or death (whichever was first), assessed up to 34 months
description: ORR was defined as the percentage of participants who had BOR of CR or PR. Tumor assessment was performed by the investigator using RECIST 1.1. ORR based on the investigator assessment was provided with a corresponding exact 95% CI which was calculated using exact method of binomial distribution.
measure: Disease Control Rate (DCR)
time frame: Date of CR, PR, or SD to date of PD or death (whichever was first), assessed up to 34 months
description: The DCR was defined as the percentage of participants who had BOR of CR, PR, or SD. Tumor assessment was performed by the investigator using RECIST 1.1. DCR based on the investigator assessment was provided with a corresponding exact 95% CI which was calculated using exact method of binomial distribution.
measure: Clinical Benefit Rate (CBR)
time frame: Date of CR, PR, or dSD to date of PD or death (whichever was first), assessed up to 34 months
description: The CBR was defined as the percentage of participants who had BOR of CR, PR, or durable SD (dSD). Tumor assessment was performed by the investigator using RECIST 1.1. Durable stable disease was defined as SD lasting greater than or equal to 23 weeks for DTC and MTC, greater than or equal to 11 weeks for ATC. A 95% CI was calculated using exact method of binomial distribution.
arm group label: E7080
arm group type: Experimental
intervention type: Drug
intervention name: E7080 capsule
description: E7080 is administered as continuous once daily dosing in an uncontrolled manner
arm group label: E7080
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Thyroid Neoplasms
mesh term: Thyroid Diseases
mesh term: Lenvatinib
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 