<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/NCT02207309</url>
  </required_header>
  <id_info>
    <org_study_id>NPM001</org_study_id>
    <secondary_id>2013-000522-58</secondary_id>
    <nct_id>NCT02207309</nct_id>
  </id_info>
  <brief_title>Pazopanib Maintenance Phase II</brief_title>
  <official_title>A Randomized, Double Blind, Phase II Trial of Pazopanib Versus Placebo as Maintenance Therapy in Patients With Retroperitoneal and Visceral High-risk Soft Tissue Sarcomas Following Prior Neo- and/or Adjuvant Doxorubicin / Ifosfamide Chemotherapy With Regional Hyperthermia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ludwig-Maximilians - University of Munich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ludwig-Maximilians - University of Munich</source>
  <brief_summary>
    <textblock>
      This trial compares pazopanib to placebo as maintenance treatment over 2 years in patients&#xD;
      with retroperitoneal and visceral high-risk soft tissue sarcomas after multimodal treatment&#xD;
      including prior neo- and/or adjuvant doxorubicin / ifosfamide chemotherapy with regional&#xD;
      hyperthermia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    poor recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">June 22, 2015</start_date>
  <completion_date type="Actual">July 29, 2016</completion_date>
  <primary_completion_date type="Actual">July 29, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>after 58 events have occurred, at the latest 27 month after the final patient is recruited</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>after 58 events have occurred, at the latest 27 month after the final patient is recruited</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Sarcoma</condition>
  <arm_group>
    <arm_group_label>Pazopanib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>800mg, oral, 24 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>800mg, oral, 24 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pazopanib</intervention_name>
    <arm_group_label>Pazopanib</arm_group_label>
    <other_name>Votrient</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for Pazopanib)</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must provide written informed consent prior to performance of study-specific&#xD;
             procedures or assessments and must be willing to comply with treatment and follow up&#xD;
&#xD;
          -  Patients must have histological evidence of high-grade soft tissue sarcoma (grade 2 -&#xD;
             3) according to the FNLCC grading system, tumor size ≥ 5 cm and deep localization with&#xD;
             regard to the superficial fascia, excluding the following tumor types:&#xD;
&#xD;
               -  Embryonal rhabdomyosarcoma&#xD;
&#xD;
               -  Chondrosarcoma (excluding extraskeletal myxoid chondrosarcoma)&#xD;
&#xD;
               -  Osteosarcoma (excluding extraskeletal osteosarcoma)&#xD;
&#xD;
               -  Ewing tumors / primitive neuroectodermal tumor (PNET)&#xD;
&#xD;
               -  Gastro-intestinal stromal tumors (GIST)&#xD;
&#xD;
               -  Dermatofibrosarcoma protuberans&#xD;
&#xD;
          -  Patients who had undergone previous surgery with inadequate margins (tumour-free&#xD;
             margins ≤1 cm or margins contaminated) are eligible if thermochemotherapy has been&#xD;
             started within 8 weeks after surgery&#xD;
&#xD;
          -  Unstained slides and ideally tumour blocks must be available for histological central&#xD;
             review&#xD;
&#xD;
          -  Completed 4 to 8 cycles of thermochemotherapy with doxorubicin and ifosfamide at least&#xD;
             21 days but no more than 42 days prior to study entry&#xD;
&#xD;
          -  No evidence of disease following completion of first-line thermochemotherapy and&#xD;
             within ≤ 21 days of study entry&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  No other prior chemotherapy except thermochemotherapy with doxorubicin and ifosfamide&#xD;
&#xD;
          -  Adequate organ system function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No prior or concurrent second primary malignant tumors (except adequately treated in&#xD;
             situ carcinoma of cervix, or basal cell carcinoma)&#xD;
&#xD;
          -  No symptomatic or known Central nervous system (CNS) metastases at baseline&#xD;
&#xD;
          -  Clinically significant gastrointestinal abnormalities that may increase the risk for&#xD;
             gastrointestinal bleeding including, but not limited to:&#xD;
&#xD;
               -  Active peptic ulcer disease&#xD;
&#xD;
               -  Known intraluminal metastatic lesion/s with risk of bleeding&#xD;
&#xD;
               -  Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease), or other&#xD;
                  gastrointestinal conditions with increased risk of perforation&#xD;
&#xD;
               -  History of abdominal fistula, gastrointestinal perforation, or intra abdominal&#xD;
                  abscess within 28 days prior to beginning study treatment.&#xD;
&#xD;
          -  Clinically significant gastrointestinal abnormalities that may affect absorption of&#xD;
             investigational product including, but not limited to:&#xD;
&#xD;
               -  Malabsorption syndrome&#xD;
&#xD;
               -  Major resection of the stomach or small bowel.&#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:&#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) (See Appendix D for description)&#xD;
&#xD;
          -  Poorly controlled hypertension (SBP of ≤ 150 mmHg or DBP of ≤95 mmHg is acceptable&#xD;
             provided that BP will be treated and monitored at least weekly. The goal is to attain&#xD;
             controlled hypertension within 4 weeks of start of IMP which is defined as grade ≤1&#xD;
             hypertension CTCAE Version 4.0)&#xD;
&#xD;
          -  NYHA II at Screening for Patients &gt; 65 years&#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;
        Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating&#xD;
        agents for at least 6 weeks are eligible&#xD;
&#xD;
          -  Major surgery or trauma within 28 days prior to first dose of investigational product&#xD;
             and/or presence of any non-healing wound, fracture, or ulcer (procedures such as&#xD;
             catheter 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 tumour 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).&#xD;
&#xD;
               -  Large protruding endobronchial lesions in the main or lobar bronchi are excluded;&#xD;
                  however, endobronchial lesions in the segmented bronchi are allowed.&#xD;
&#xD;
               -  Lesions extensively infiltrating the main or lobar bronchi are excluded; however,&#xD;
                  minor infiltrations in the wall of the bronchi are allowed.&#xD;
&#xD;
          -  Recent hemoptysis (≥½ teaspoon of red blood within 8 weeks before first dose of study&#xD;
             drug).&#xD;
&#xD;
          -  Any serious and/or unstable pre-existing medical, psychiatric, or other condition that&#xD;
             could interfere with subject's safety, provision of informed consent, or compliance to&#xD;
             study procedures.&#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, biologic therapy, investigational therapy or&#xD;
                  hormonal therapy within 14 days or five half-lives of a drug (whichever is&#xD;
                  longer) prior to the first dose of pazopanib&#xD;
&#xD;
          -  Administration of any non-oncologic investigational drug within 30 days or 5 half&#xD;
             lives whichever is longer prior to receiving the first dose of study treatment&#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;
      </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>Lars Lindner, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ludwig-Maximilians - University of Munich</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ludwig-Maximilians University of Munich, Klinikum Großhadern</name>
      <address>
        <city>Munich</city>
        <state>Bavaria</state>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <last_update_submitted>November 8, 2017</last_update_submitted>
  <last_update_submitted_qc>November 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ludwig-Maximilians - University of Munich</investigator_affiliation>
    <investigator_full_name>Lars Lindner</investigator_full_name>
    <investigator_title>PD Dr. med.</investigator_title>
  </responsible_party>
  <keyword>high-risk soft tissue sarcoma</keyword>
  <keyword>pazopanib</keyword>
  <keyword>retroperitoneal soft tissue sarcoma</keyword>
  <keyword>visceral soft tissue sarcoma</keyword>
  <keyword>votrient</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>October 25, 2022</submitted>
    <returned>September 5, 2023</returned>
  </pending_results>
  <!-- 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/NCT02207309
org study id: NPM001
secondary id: 2013-000522-58
nct id: NCT02207309
lead sponsor: 
This trial compares pazopanib to placebo as maintenance treatment over 2 years in patients
      with retroperitoneal and visceral high-risk soft tissue sarcomas after multimodal treatment
      including prior neo- and/or adjuvant doxorubicin / ifosfamide chemotherapy with regional
      hyperthermia.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Progression-free Survival (PFS)
time frame: after 58 events have occurred, at the latest 27 month after the final patient is recruited
measure: Overall Survival (OS)
time frame: after 58 events have occurred, at the latest 27 month after the final patient is recruited
arm group label: Pazopanib
arm group type: Active Comparator
description: 800mg, oral, 24 months
arm group label: Placebo
arm group type: Placebo Comparator
description: 800mg, oral, 24 months
intervention type: Drug
intervention name: Pazopanib
arm group label: Pazopanib
other name: Votrient
intervention type: Drug
intervention name: Placebo (for Pazopanib)
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lars Lindner, MD, PhD
role: Principal Investigator
affiliation: Ludwig-Maximilians - University of Munich
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Ludwig-Maximilians - University of Munich
investigator full name: Lars Lindner
investigator title: PD Dr. med.
mesh term: Sarcoma
submitted: October 25, 2022
returned: September 5, 2023