<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/NCT01666418</url>
  </required_header>
  <id_info>
    <org_study_id>SZ10ON01</org_study_id>
    <nct_id>NCT01666418</nct_id>
  </id_info>
  <brief_title>Pilot Study Investigating the Metabolic Activity and Transcriptional Profiling in Vivo in Tumor Biopsies in Melanoma Patients During Treatment With Pazopanib Alone and in Combination With Paclitaxel</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Zurich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Zurich</source>
  <brief_summary>
    <textblock>
      This is an open, monocentric, pilot study to determine the metabolic activity&#xD;
      (glucose-uptake) in vivo during monotherapy with pazopanib in comparison to combination&#xD;
      therapy with pazopanib plus paclitaxel and to investigate the transcriptional profile of&#xD;
      cutaneous melanoma metastasis before and during the therapy (pazopanib vs. pazopanib plus&#xD;
      paclitaxel) in subjects with unresectable Stage III or Stage IV melanoma who have not&#xD;
      received prior cytotoxic chemotherapy.&#xD;
&#xD;
      Primary Objective:&#xD;
&#xD;
      Evaluation of metabolic activity in vivo&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
      Determination of changes in gene expression profiling Evaluation of the antitumor activity of&#xD;
      the combination in terms of progression free survival (PFS). Changes in S100 and LDH during&#xD;
      therapy at the same time points as FDG-PET/CT (a combined serum measurement of S100 and LDH)&#xD;
&#xD;
        -  Trial with medicinal product&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">October 2014</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>Evaluation of metabolic activity in vivo</measure>
    <time_frame>84 days ( Baseline, Day 10, Day 70)</time_frame>
    <description>The primary efficacy objective is to evaluate the metabolic activity in vivo through standardising the uptake value (SUV) in the FDG-PET/CT in comparison of the SUV between baseline, after pazopanib alone (day 10) and after pazopanib plus paclitaxel (day 70).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determination of changes in gene expression profiling</measure>
    <time_frame>84 days ( Baseline, Day 10, Day 70)</time_frame>
    <description>Determination of changes in gene expression profiling on exon level in all patients with (sub)-cutaneous or superficial lymph node metastases (of melanoma) during pazopanib and pazopanib plus paclitaxel therapy in comparison to pretreatment profile</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the antitumor activity of the combination in terms of progression free survival (PFS)</measure>
    <time_frame>112 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in S100 and LDH during therapy at the same time points as FDG-PET/CT (a combined serum measurement of S100 and LDH)</measure>
    <time_frame>84 days ( Baseline, Day 10, Day 70)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>Pazopanib/Paclitaxel</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pazopanib/Paclitaxel</intervention_name>
    <arm_group_label>Pazopanib/Paclitaxel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Diagnosis of histologically or cytologically confirmed melanoma stage III or IV.&#xD;
&#xD;
          -  Fresh tumor tissue must be provided for all subjects for biomarker analysis before&#xD;
             (within 14 days prior to treatment start) and during (on day 10 of the pazopanib&#xD;
             monotherapy and the last day of the treatment with pazopanib, day 70) treatment with&#xD;
             investigational product (asservation in RNAlater, for kryo asservation, and for cell&#xD;
             cultures)&#xD;
&#xD;
          -  Assessable metastases (skin or superficial lymph nodes with a minimal diameter 1 cm)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.&#xD;
&#xD;
          -  Adequate organ system function&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Prior malignancy.&#xD;
&#xD;
          -  Central nervous system (CNS) metastases&#xD;
&#xD;
          -  Corrected QT interval (QTc) &gt; 480 msecs using Bazett's formula.&#xD;
&#xD;
          -  History of any one or more of the following cardiovascular conditions within the past&#xD;
             6 months:&#xD;
&#xD;
               -  Cardiac angioplasty or stenting;&#xD;
&#xD;
               -  Myocardial infarction;&#xD;
&#xD;
               -  Unstable angina;&#xD;
&#xD;
               -  Coronary artery bypass graft surgery;&#xD;
&#xD;
               -  Symptomatic peripheral vascular disease;&#xD;
&#xD;
               -  Class III or IV congestive heart failure, as defined by the New York Heart&#xD;
                  Association (NYHA).&#xD;
&#xD;
          -  Poorly controlled hypertension&#xD;
&#xD;
          -  History of cerebrovascular accident including transient ischemic attack (TIA),&#xD;
             pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.&#xD;
&#xD;
          -  Presence of uncontrolled infection&#xD;
&#xD;
          -  Clinically significant gastrointestinal abnormalities that may increase the risk for&#xD;
             gastrointestinal bleeding&#xD;
&#xD;
          -  Evidence of active bleeding or bleeding diathesis&#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.&#xD;
&#xD;
          -  Prior exposure to the study drug pazopanib&#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>Reinhard Dummer, Professor MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Zurich, Division of Dermatology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Zurich, Division of Dermatology</name>
      <address>
        <city>Zurich</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>August 8, 2012</study_first_submitted>
  <study_first_submitted_qc>August 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>October 11, 2018</last_update_submitted>
  <last_update_submitted_qc>October 11, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 16, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01666418
org study id: SZ10ON01
nct id: NCT01666418
lead sponsor: 
This is an open, monocentric, pilot study to determine the metabolic activity
      (glucose-uptake) in vivo during monotherapy with pazopanib in comparison to combination
      therapy with pazopanib plus paclitaxel and to investigate the transcriptional profile of
      cutaneous melanoma metastasis before and during the therapy (pazopanib vs. pazopanib plus
      paclitaxel) in subjects with unresectable Stage III or Stage IV melanoma who have not
      received prior cytotoxic chemotherapy.

      Primary Objective:

      Evaluation of metabolic activity in vivo

      Secondary Objective:

      Determination of changes in gene expression profiling Evaluation of the antitumor activity of
      the combination in terms of progression free survival (PFS). Changes in S100 and LDH during
      therapy at the same time points as FDG-PET/CT (a combined serum measurement of S100 and LDH)

        -  Trial with medicinal product
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Evaluation of metabolic activity in vivo
time frame: 84 days ( Baseline, Day 10, Day 70)
description: The primary efficacy objective is to evaluate the metabolic activity in vivo through standardising the uptake value (SUV) in the FDG-PET/CT in comparison of the SUV between baseline, after pazopanib alone (day 10) and after pazopanib plus paclitaxel (day 70).
measure: Determination of changes in gene expression profiling
time frame: 84 days ( Baseline, Day 10, Day 70)
description: Determination of changes in gene expression profiling on exon level in all patients with (sub)-cutaneous or superficial lymph node metastases (of melanoma) during pazopanib and pazopanib plus paclitaxel therapy in comparison to pretreatment profile
measure: Evaluation of the antitumor activity of the combination in terms of progression free survival (PFS)
time frame: 112 days
measure: Changes in S100 and LDH during therapy at the same time points as FDG-PET/CT (a combined serum measurement of S100 and LDH)
time frame: 84 days ( Baseline, Day 10, Day 70)
arm group label: Pazopanib/Paclitaxel
arm group type: Other
intervention type: Drug
intervention name: Pazopanib/Paclitaxel
arm group label: Pazopanib/Paclitaxel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Reinhard Dummer, Professor MD
role: Principal Investigator
affiliation: University Hospital Zurich, Division of Dermatology
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Paclitaxel