<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/NCT02193152</url>
  </required_header>
  <id_info>
    <org_study_id>201408009</org_study_id>
    <nct_id>NCT02193152</nct_id>
  </id_info>
  <brief_title>Pazopanib in Molecularly Selected Patients With Advanced NSCLC</brief_title>
  <official_title>A Pilot Study of Pazopanib in Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate how participants with advanced non-small cell lung&#xD;
      cancer (NSCLC) that have certain abnormalities in the pazopanib target genes respond to&#xD;
      pazopanib treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There has been a limited benefit from anti-angiogenesis drugs in patients with NSCLC.&#xD;
      Bevacizumab provides a modest survival improvement when added to chemotherapy and VEGFR&#xD;
      tyrosine kinase inhibitors have been associated with minimal efficacy as single agents and&#xD;
      increased toxicity when combined with chemotherapy. We postulate that the response rates and&#xD;
      survival may be improved with a better selection of patients based on abnormalities of the&#xD;
      targets for the drugs. According to the preliminary data from the cancer genome atlas (TCGA),&#xD;
      the targets of pazopanib are altered in 28% of patients with adenocarcinoma and 24% of&#xD;
      patients with squamous cell lung cancer. Since, despite the molecular selection prior to&#xD;
      treatment, only a small percentage of patients will benefit from the treatment, we plan to&#xD;
      further investigate those patients with whole exome sequencing in both the pre-treatment&#xD;
      samples to identify the predictors for response and at the time of progression, with repeated&#xD;
      biopsy, in an attempt to identify the predictors for secondary resistance. By identifying&#xD;
      more reliable predictors for response to pazopanib, our study may help to establish its role&#xD;
      in the treatment of NSCLC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Terminated by sponsor&#xD;
  </why_stopped>
  <start_date type="Actual">April 27, 2015</start_date>
  <completion_date type="Actual">December 24, 2019</completion_date>
  <primary_completion_date type="Actual">December 24, 2019</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>Response Rate</measure>
    <time_frame>Until the end of treatment (median length of treatment=85.5 days (full range 25-334 days)</time_frame>
    <description>Participants should be re-evaluated for response 8 weeks after initiation of pazopanib and then every 8 weeks thereafter. In addition to a baseline scan, confirmatory scans should also be obtained not less than 4 weeks following initial documentation of objective response.&#xD;
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009].&#xD;
Response rate is the percentage of participants with a complete or partial response&#xD;
Complete response=Disappearance of all target and non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (&lt;10 mm short axis).&#xD;
Partial response=At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>Until progressive disease or death (median follow-up 174 days, full range 41 days-545 days)</time_frame>
    <description>Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. There is no limit on following for progression-free survival besides death of the participant.&#xD;
Progressive disease=At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Outcomes Associated With Specific Mutations</measure>
    <time_frame>Until time of death (an expected average of 8 months)</time_frame>
    <description>Participants are followed until death.&#xD;
All participants will undergo next generation sequencing prior to enrollment into the study.&#xD;
Initial predictors are the mutations in VEGFR or PDGFR, but sequencing will be used to evaluate for other predictors as well.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mutational Predictors for Extreme Responders</measure>
    <time_frame>Until end of treatment (an expected average of 8 months)</time_frame>
    <description>-Whole exome and transcriptome sequencing will be performed in 10 participants, including 4 to 6 responders and 4 to 6 non-responders in order to identify the predictors for benefit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mechanisms of Secondary Resistance.</measure>
    <time_frame>Until the time of progressive disease (an expected average of 8 months)</time_frame>
    <description>-Participants will also undergo next generation sequencing at the time of progression in an attempt to identify the mechanisms for secondary resistance.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Carcinoma, Non-Small Cell Lung</condition>
  <condition>Non-Small Cell Lung Cancer</condition>
  <condition>Nonsmall Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment: Pazopanib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pazopanib 800 mg daily should be taken orally without food at least one hour before or two hours after a meal.&#xD;
One cycle of pazopanib is 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pazopanib</intervention_name>
    <arm_group_label>Treatment: Pazopanib</arm_group_label>
    <other_name>GW786034</other_name>
    <other_name>Votrient®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed diagnosis of advanced (metastatic or unresectable) non-small&#xD;
             cell lung cancer (NSCLC) with mutations, rearrangement and fusion involving RET&#xD;
             oncogene, or abnormalities in the pazopanib target genes defined as VEGFR1-3, PDGFRA,&#xD;
             PDGFRB, or TP53 with abnormalities including deletion, insertion, early stop codon,&#xD;
             and/or nonsynonymous mutations with functional consequences. CLIA certified lab&#xD;
             testing for pazopanib target genes using cell free DNA from peripheral blood and/or&#xD;
             assays performed on tumor tissues are acceptable.&#xD;
&#xD;
          -  Evaluable disease by imaging or physical exam OR measurable disease defined as at&#xD;
             least one lesion that can be accurately measured in at least one dimension (longest&#xD;
             diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10&#xD;
             mm with calipers by clinical exam.&#xD;
&#xD;
          -  Failed at least one standard chemotherapeutic treatment for NSCLC.&#xD;
&#xD;
          -  At least 18 years of age.&#xD;
&#xD;
          -  ECOG performance status ≤ 2&#xD;
&#xD;
          -  Normal bone marrow and organ function as defined below:&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1,500/mcl&#xD;
&#xD;
               -  Platelets ≥ 100,000/mcl&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  PT or INR ≤ 1.2 x IULN&#xD;
&#xD;
               -  aPTT ≤ 1.2 x IULN&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x IULN&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN&#xD;
&#xD;
               -  Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 30 mL/min/1.73 m2 for patients&#xD;
                  with creatinine levels above 1.5 mg/dL&#xD;
&#xD;
               -  UPC &lt; 1 or, if UPC ≥ 1, 24-hour urine protein &lt; 1 g; use of urine dipstick for&#xD;
                  renal function assessment is not acceptable.&#xD;
&#xD;
          -  Patients receiving anticoagulation therapy are eligible if their INR is stable and&#xD;
             within the recommended range for the desired level of anticoagulation.&#xD;
&#xD;
          -  Ability to swallow and retain oral tablets.&#xD;
&#xD;
          -  Women of childbearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control, abstinence) prior to study entry and for&#xD;
             the duration of study participation. Should a woman become pregnant or suspect she is&#xD;
             pregnant while participating in this study, she must inform her treating physician&#xD;
             immediately.&#xD;
&#xD;
          -  Ability to understand and willingness to sign an IRB approved written informed consent&#xD;
             document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with any of the following anti-cancer therapies:&#xD;
&#xD;
               -  Radiation therapy, surgery, or tumor embolization within 14 days prior to the&#xD;
                  first dose of pazopanib OR&#xD;
&#xD;
               -  Chemotherapy, immunotherapy, investigational therapy or hormonal therapy within&#xD;
                  14 days prior to the first dose of pazopanib&#xD;
&#xD;
          -  Prior treatment with any VEGFR tyrosine kinase inhibitor.&#xD;
&#xD;
          -  Administration of any non-oncologic investigational drug within 30 days or 5&#xD;
             half-lives (whichever is longer) prior to the first dose of pazopanib.&#xD;
&#xD;
          -  Use of a strong CYP3A4 inhibitor less than 14 days prior to initiation of study&#xD;
             treatment&#xD;
&#xD;
          -  A history of other malignancy ≤ 5 years previous with the exception of basal cell or&#xD;
             squamous cell carcinoma of the skin which were treated with local resection only or&#xD;
             carcinoma in situ of the cervix.&#xD;
&#xD;
          -  Symptomatic brain metastases. Patients with known brain metastases are allowed if they&#xD;
             are asymptomatic.&#xD;
&#xD;
          -  A history of allergic reactions attributed to compounds of similar chemical or&#xD;
             biologic composition to pazopanib or other agents used in the study.&#xD;
&#xD;
          -  Any ongoing toxicity from prior anti-cancer therapy that is &gt; grade 1 and/or that is&#xD;
             progressing in severity (except alopecia). Any IO related adverse events must be ≤&#xD;
             grade 1 to be eligible.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, uncontrolled seizure disorder, chronic underlying liver disease unrelated&#xD;
             to cancer, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  Corrected QT interval (QTc) &gt; 480 msecs.&#xD;
&#xD;
          -  History of any one or more of the following cardiovascular conditions within the past&#xD;
             6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina&#xD;
             pectoris, coronary artery bypass graft surgery, symptomatic peripheral vascular&#xD;
             disease, class III or IV congestive heart failure as defined by the New York Heart&#xD;
             Association (see Appendix B).&#xD;
&#xD;
          -  Poorly controlled hypertension (defined as systolic blood pressure of ≥ 140 mmHg or&#xD;
             diastolic blood pressure of ≥ 90 mmHg). Note: initiation or adjustment of&#xD;
             antihypertensive medication(s) is permitted prior to study entry. Following&#xD;
             antihypertensive medication initiation or adjustment, blood pressure must be&#xD;
             reassessed three times at approximately 2-minute intervals. At least 24 hours must&#xD;
             have elapsed between antihypertensive medication initiation or adjustment and blood&#xD;
             pressure measurement. These three values should be averaged to obtain the mean&#xD;
             diastolic and systolic blood pressures, which must be &lt; 140/90 mmHg in order for a&#xD;
             patient to be eligible for the study.&#xD;
&#xD;
          -  Clinically significant gastrointestinal abnormalities that may increase the risk for&#xD;
             gastrointestinal bleeding, including (but not limited to) active peptic ulcer disease,&#xD;
             known intraluminal metastatic lesions with risk of bleeding, inflammatory bowel&#xD;
             disease (e.g., ulcerative colitis, Crohn's disease) or other GI conditions with&#xD;
             increased risk of perforation, history of abdominal fistula or intra-abdominal abscess&#xD;
             within 28 days prior to beginning study treatment.&#xD;
&#xD;
          -  Clinically significant gastrointestinal abnormalities that may affect absorption of&#xD;
             pazopanib, including (but not limited to) malabsorption syndrome or major resection of&#xD;
             the stomach or small bowel.&#xD;
&#xD;
          -  History of cerebrovascular accident including transient ischemic attack, pulmonary&#xD;
             embolism (including asymptomatic or previously treated PE), or untreated deep venous&#xD;
             thrombosis within the past 6 months. Patients with recent DVT who have been treated&#xD;
             with therapeutic anti-coagulating agents for at least 6 weeks are eligible.&#xD;
&#xD;
          -  Major surgery or trauma within 28 days prior to first dose of pazopanib and/or&#xD;
             presence of any non-healing wound, fracture, or ulcer (procedures such as catheter&#xD;
             placement not considered to be major surgery).&#xD;
&#xD;
          -  Evidence of active bleeding or bleeding diathesis.&#xD;
&#xD;
          -  Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that&#xD;
             increase the risk of pulmonary hemorrhage. Note: lesions infiltrating major pulmonary&#xD;
             vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor&#xD;
             that is touching but not infiltrating (abutting) the vessels is acceptable (CT with&#xD;
             contrast is strongly recommended to evaluate such lesions). Large protruding&#xD;
             endobronchial lesions in the mail or lobar bronchi are excluded; however,&#xD;
             endobronchial lesions in the segmented bronchi are allowed. Lesions extensively&#xD;
             infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in&#xD;
             the wall of thee bronchi are allowed.&#xD;
&#xD;
          -  Recent hemoptysis (≥ ½ teaspoon of red blood within 8 weeks before first dose of&#xD;
             pazopanib).&#xD;
&#xD;
          -  Pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test&#xD;
             within 14 days of study entry.&#xD;
&#xD;
          -  Known HIV-positivity. Appropriate studies will be undertaken in patients receiving&#xD;
             combination antiretroviral therapy when indicated.&#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>Daniel Morgensztern, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 11, 2014</study_first_submitted>
  <study_first_submitted_qc>July 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 17, 2014</study_first_posted>
  <results_first_submitted>June 26, 2020</results_first_submitted>
  <results_first_submitted_qc>July 13, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 14, 2020</results_first_posted>
  <last_update_submitted>July 13, 2020</last_update_submitted>
  <last_update_submitted_qc>July 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Advanced Non-Small Cell Lung Cancer</keyword>
  <keyword>NSCLC</keyword>
  <keyword>Pazopanib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT02193152/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment: Pazopanib</title>
          <description>Pazopanib 800 mg daily should be taken orally without food at least one hour before or two hours after a meal.&#xD;
One cycle of pazopanib is 28 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment: Pazopanib</title>
          <description>Pazopanib 800 mg daily should be taken orally without food at least one hour before or two hours after a meal.&#xD;
One cycle of pazopanib is 28 days.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66.5" lower_limit="50" upper_limit="80"/>
                  </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="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </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>
          <title>Race (NIH/OMB)</title>
          <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="1"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </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>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Response Rate</title>
        <description>Participants should be re-evaluated for response 8 weeks after initiation of pazopanib and then every 8 weeks thereafter. In addition to a baseline scan, confirmatory scans should also be obtained not less than 4 weeks following initial documentation of objective response.&#xD;
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009].&#xD;
Response rate is the percentage of participants with a complete or partial response&#xD;
Complete response=Disappearance of all target and non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (&lt;10 mm short axis).&#xD;
Partial response=At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters</description>
        <time_frame>Until the end of treatment (median length of treatment=85.5 days (full range 25-334 days)</time_frame>
        <population>4 participants were not evaluable for this outcome measure because they were removed from treatment prior to the re-evaluation response at 8 weeks</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment: Pazopanib</title>
            <description>Pazopanib 800 mg daily should be taken orally without food at least one hour before or two hours after a meal.&#xD;
One cycle of pazopanib is 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Response Rate</title>
          <description>Participants should be re-evaluated for response 8 weeks after initiation of pazopanib and then every 8 weeks thereafter. In addition to a baseline scan, confirmatory scans should also be obtained not less than 4 weeks following initial documentation of objective response.&#xD;
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009].&#xD;
Response rate is the percentage of participants with a complete or partial response&#xD;
Complete response=Disappearance of all target and non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (&lt;10 mm short axis).&#xD;
Partial response=At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters</description>
          <population>4 participants were not evaluable for this outcome measure because they were removed from treatment prior to the re-evaluation response at 8 weeks</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. There is no limit on following for progression-free survival besides death of the participant.&#xD;
Progressive disease=At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).</description>
        <time_frame>Until progressive disease or death (median follow-up 174 days, full range 41 days-545 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment: Pazopanib</title>
            <description>Pazopanib 800 mg daily should be taken orally without food at least one hour before or two hours after a meal.&#xD;
One cycle of pazopanib is 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. There is no limit on following for progression-free survival besides death of the participant.&#xD;
Progressive disease=At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).</description>
          <units>weeks</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.25" lower_limit="3.5" upper_limit="47.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Outcomes Associated With Specific Mutations</title>
        <description>Participants are followed until death.&#xD;
All participants will undergo next generation sequencing prior to enrollment into the study.&#xD;
Initial predictors are the mutations in VEGFR or PDGFR, but sequencing will be used to evaluate for other predictors as well.</description>
        <time_frame>Until time of death (an expected average of 8 months)</time_frame>
        <population>The data was not collected for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment: Pazopanib</title>
            <description>Pazopanib 800 mg daily should be taken orally without food at least one hour before or two hours after a meal.&#xD;
One cycle of pazopanib is 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Outcomes Associated With Specific Mutations</title>
          <description>Participants are followed until death.&#xD;
All participants will undergo next generation sequencing prior to enrollment into the study.&#xD;
Initial predictors are the mutations in VEGFR or PDGFR, but sequencing will be used to evaluate for other predictors as well.</description>
          <population>The data was not collected for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mutational Predictors for Extreme Responders</title>
        <description>-Whole exome and transcriptome sequencing will be performed in 10 participants, including 4 to 6 responders and 4 to 6 non-responders in order to identify the predictors for benefit.</description>
        <time_frame>Until end of treatment (an expected average of 8 months)</time_frame>
        <population>The data was not collected for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment: Pazopanib</title>
            <description>Pazopanib 800 mg daily should be taken orally without food at least one hour before or two hours after a meal.&#xD;
One cycle of pazopanib is 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mutational Predictors for Extreme Responders</title>
          <description>-Whole exome and transcriptome sequencing will be performed in 10 participants, including 4 to 6 responders and 4 to 6 non-responders in order to identify the predictors for benefit.</description>
          <population>The data was not collected for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mechanisms of Secondary Resistance.</title>
        <description>-Participants will also undergo next generation sequencing at the time of progression in an attempt to identify the mechanisms for secondary resistance.</description>
        <time_frame>Until the time of progressive disease (an expected average of 8 months)</time_frame>
        <population>The data was not collected for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment: Pazopanib</title>
            <description>Pazopanib 800 mg daily should be taken orally without food at least one hour before or two hours after a meal.&#xD;
One cycle of pazopanib is 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mechanisms of Secondary Resistance.</title>
          <description>-Participants will also undergo next generation sequencing at the time of progression in an attempt to identify the mechanisms for secondary resistance.</description>
          <population>The data was not collected for this outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from study start through 30 days after completion of treatment (median treatment length 85.5 days (full range=25 days-334 days)).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Treatment: Pazopanib</title>
          <description>Pazopanib 800 mg daily should be taken orally without food at least one hour before or two hours after a meal.&#xD;
One cycle of pazopanib is 28 days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</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="14" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="16"/>
              </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="16"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</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="16" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothryoidism</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Visual changes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Gingival pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Leg pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Foot pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Left side pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hip pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Shoulder pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Papulopustular rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </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="7" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Left shoulder pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Polyuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </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="12" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Bronchopulmonary hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Voice alteration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </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="6" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nail changes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysethesia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flashes</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Daniel Morgensztern, M.D.</name_or_title>
      <organization>Washington University School of Medicine</organization>
      <phone>314-362-5737</phone>
      <email>danielmorgensztern@wustl.edu</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/NCT02193152
org study id: 201408009
nct id: NCT02193152
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to evaluate how participants with advanced non-small cell lung
      cancer (NSCLC) that have certain abnormalities in the pazopanib target genes respond to
      pazopanib treatment.
There has been a limited benefit from anti-angiogenesis drugs in patients with NSCLC.
      Bevacizumab provides a modest survival improvement when added to chemotherapy and VEGFR
      tyrosine kinase inhibitors have been associated with minimal efficacy as single agents and
      increased toxicity when combined with chemotherapy. We postulate that the response rates and
      survival may be improved with a better selection of patients based on abnormalities of the
      targets for the drugs. According to the preliminary data from the cancer genome atlas (TCGA),
      the targets of pazopanib are altered in 28% of patients with adenocarcinoma and 24% of
      patients with squamous cell lung cancer. Since, despite the molecular selection prior to
      treatment, only a small percentage of patients will benefit from the treatment, we plan to
      further investigate those patients with whole exome sequencing in both the pre-treatment
      samples to identify the predictors for response and at the time of progression, with repeated
      biopsy, in an attempt to identify the predictors for secondary resistance. By identifying
      more reliable predictors for response to pazopanib, our study may help to establish its role
      in the treatment of NSCLC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response Rate
time frame: Until the end of treatment (median length of treatment=85.5 days (full range 25-334 days)
description: Participants should be re-evaluated for response 8 weeks after initiation of pazopanib and then every 8 weeks thereafter. In addition to a baseline scan, confirmatory scans should also be obtained not less than 4 weeks following initial documentation of objective response.
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009].
Response rate is the percentage of participants with a complete or partial response
Complete response=Disappearance of all target and non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
Partial response=At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters
measure: Progression-free Survival (PFS)
time frame: Until progressive disease or death (median follow-up 174 days, full range 41 days-545 days)
description: Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. There is no limit on following for progression-free survival besides death of the participant.
Progressive disease=At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
measure: Outcomes Associated With Specific Mutations
time frame: Until time of death (an expected average of 8 months)
description: Participants are followed until death.
All participants will undergo next generation sequencing prior to enrollment into the study.
Initial predictors are the mutations in VEGFR or PDGFR, but sequencing will be used to evaluate for other predictors as well.
measure: Mutational Predictors for Extreme Responders
time frame: Until end of treatment (an expected average of 8 months)
description: -Whole exome and transcriptome sequencing will be performed in 10 participants, including 4 to 6 responders and 4 to 6 non-responders in order to identify the predictors for benefit.
measure: Mechanisms of Secondary Resistance.
time frame: Until the time of progressive disease (an expected average of 8 months)
description: -Participants will also undergo next generation sequencing at the time of progression in an attempt to identify the mechanisms for secondary resistance.
arm group label: Treatment: Pazopanib
arm group type: Experimental
description: Pazopanib 800 mg daily should be taken orally without food at least one hour before or two hours after a meal.
One cycle of pazopanib is 28 days.
intervention type: Drug
intervention name: Pazopanib
arm group label: Treatment: Pazopanib
other name: GW786034
other name: Votrient®
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Daniel Morgensztern, M.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 