<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/NCT01692496</url>
  </required_header>
  <id_info>
    <org_study_id>GEIS-30</org_study_id>
    <secondary_id>2012-002745-38</secondary_id>
    <nct_id>NCT01692496</nct_id>
  </id_info>
  <brief_title>Activity and Tolerability of Pazopanib in Advanced and/or Metastatic Liposarcoma. A Phase II Clinical Trial</brief_title>
  <official_title>Phase II Clinical Trial of Pazopanib to Evaluate the Activity and Tolerability in Patients With Advanced and/or Metastatic Liposarcoma Who Have Relapsed Following Standard Therapies or for Whom no Standard Therapy Exists</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Grupo Espanol de Investigacion en Sarcomas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Grupo Espanol de Investigacion en Sarcomas</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Soft tissue and bone sarcomas are rare malignant tumors, which encompasses a large family of&#xD;
      more than 50 histologically distinct tumor subtypes, all of which share a putative&#xD;
      mesenchymal origin. In the case of soft tissue sarcomas (STS) surgical excision is the&#xD;
      mainstay of treatment, but despite curative surgery, around half of patients develop distant&#xD;
      metastases and die from disease. Few therapeutic approaches are currently available to&#xD;
      patients with unresectable, locally advanced, or metastatic STS and only anthracyclines,&#xD;
      ifosfamide and trabectedin have shown activity, with response rates of 20-40% in previously&#xD;
      untreated patients. Recent and ongoing trials have investigated a variety of combination&#xD;
      chemotherapeutic regimens (variously employing ifosfamide, doxorubicin, gemcitabine,&#xD;
      temozolomide, vincristine, cisplatin, and dacarbazine, among others) as well as targeted&#xD;
      therapies, which in some cases have yielded improvements in response rate but which have had&#xD;
      little impact on survival. No other medical option is currently available, and the median&#xD;
      survival of patients with soft-tissue sarcoma with non-resectable metastases is around 12-15&#xD;
      months, and approximately 8 months after second line chemotherapy.&#xD;
&#xD;
      Liposarcomas are STS which account for at least 20% of all STS in adults. They can be further&#xD;
      classified into 3 histologically and biologically different subtypes: well-differentiated&#xD;
      liposarcoma/dedifferentiated liposarcoma (ALT-WD), myxoid or round cell liposarcoma and&#xD;
      pleomorphic liposarcoma.&#xD;
&#xD;
      ALT-WD liposarcomas are locally aggressive rarely metastasizing tumors characterized by ring&#xD;
      or giant marker chromosomes on the cytogenetic analysis and by amplification of the 12q13-21&#xD;
      region on Fluorescence In Situ Hybridization (FISH) (MDM2, CDK4 and HMGIC). They account for&#xD;
      about 40% iv of liposarcomas with a 5 year Overall survival (OS) around 80%. In a series of&#xD;
      WD/DD treated with several regimens response rate was 12.5% OS 15 months and median PFS 3.6&#xD;
      months(95 confidence interval (CI): 3.3-5.9) Mixoid /round cell liposarcoma accounts for&#xD;
      45-50% of all liposarcomas. They tend to metastasize to unusual soft tissue and bone&#xD;
      locations. High histologic grade with more than 5% of round cell component is associated with&#xD;
      a 5-year OS of 50% approximately. They are characterized by t(23;16)(q13-14;p11) which leads&#xD;
      to the fusion of CHOP and TLS genes Pleomorphic liposarcoma accounts for approximately 5-10%&#xD;
      of all liposarcomas, characterized by high grade features with frequent and early lung&#xD;
      metastasis and cytogenetically by high chromosome counts and complex structural&#xD;
      rearrangements.&#xD;
&#xD;
      VEGF is expressed in many STS in which increased expression is associated with higher grade&#xD;
      and worse prognosis.&#xD;
&#xD;
      Pazopanib is an oral angiogenesis inhibitor that targets mainly VEGFR, PDGFR and c-kit.&#xD;
      Recently the results of a phase II trial of pazopanib in STS have been published. It was a&#xD;
      four-cohort 2-stages study. The liposarcoma stratum was closed after the first stage because&#xD;
      of a PFS at 12 weeks of 17% (3 out of 17 patients did not progressed after 12 weeks). After&#xD;
      central pathologic review, 2 other patients initially classified as other STS were found to&#xD;
      have liposarcoma with stable disease at 12 weeks (5/19: 26% PFS12w), thus fulfilling criteria&#xD;
      for cohort expansion. Phase II study had been completed and in phase III study patients with&#xD;
      liposarcomas were excluded so therefore data on the liposarcoma cohort are inconclusive.&#xD;
&#xD;
      Furthermore the positive results of the phase III study PALETTE have been recently&#xD;
      communicated, encouraging this treatment in other sarcomas: progression-free survival (PFS)&#xD;
      per independent review was significantly prolonged with pazopanib (median: 4.6 vs 1.5 months;&#xD;
      HR=0.31, 95% CI 0.24-0.40; P&lt;0.0001). The interim analysis for overall survival shows a&#xD;
      statistically non-significant improvement of pazopanib vs placebo (median: 11.9 vs 10.4&#xD;
      months, HR=0.83, 95% CI 0.62-1.09).&#xD;
&#xD;
      Soluble factors associated with efficacy and toxicity of pazopanib in these patients had been&#xD;
      also reported. Decreases in VEGFR2 and increase in PlGF were both associated with toxicity&#xD;
      (HTA and TSH elevation) and poorer prognosis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 29, 2013</start_date>
  <completion_date type="Actual">March 2, 2018</completion_date>
  <primary_completion_date type="Actual">March 2018</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>Progression-free Survival (PFS) Assessed 12 Weeks After Start of Treatment</measure>
    <time_frame>12 weeks after start of treatment</time_frame>
    <description>The primary objective of this study is to evaluate the activity of Pazopanib in patients with advanced and/or metastatic liposarcoma by means of progression-free survival (PFS) assessed 12 weeks after start of treatment. (According the RECIST criteria 1.1 and central radiology review).&#xD;
Progression was defined according to RECIST criteria 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Progression Free Survival (Median PFS)</measure>
    <time_frame>Imaging studies repeated every 6 weeks for the first 12 weeks and every 8 weeks up to 36 months.</time_frame>
    <description>Overall progression free survival will be computed from the date of start of treatment to the first documented date of progression or the date of death, whatever the cause. Patients alive and free from progression at the time of the analysis will be censored at the date of last follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With Objective Tumor Response (OR)</measure>
    <time_frame>6 weeks and 12 weeks</time_frame>
    <description>Objective tumor response, measured according to the RECIST 1.1 criteria (central reviewing) at 6 and 12 weeks.&#xD;
Response criteria are essentially based on a set of measurable lesions identified at baseline as target lesions, and followed until disease progression.&#xD;
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Every 12 weeks from disease progression up to 36 months.</time_frame>
    <description>It will be computed from the date of start of treatment to the date of death, whatever the cause. Patients alive or lost for follow-up at the time of the analysis will be censored at the date of last follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate</measure>
    <time_frame>Imaging studies required to investigate known disease should be repeated every 6 weeks for the first 12 weeks and every 8 weeks up to 36 months.</time_frame>
    <description>Patients who achieve complete response (CR), partial response (PR), or stable disease (SD) for 6 months or more and an improvement of symptoms will be considered as having derived clinical benefit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Growth Modulation Index (GMI)</measure>
    <time_frame>Imaging studies required to investigate known disease should be repeated every 6 weeks for the first 12 weeks and every 8 weeks up to 36 months. At patient progression confirmed by means RECIST criteria V 1.1</time_frame>
    <description>GMI is the ratio between time to progression (TTP) with pazopanib (TTPp) divided by the TTPp-1 with the previous line of therapy.&#xD;
GMI index values higher than 1 indicate that Pazopanib treatment has an increased time to progression when compared to previous line of treatment.&#xD;
GMI index values lower than 1 indicate that Pazopanib treatment has a reduced time to progression when compared to previous line of treatment.&#xD;
Higher GMI values are associated to a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety Profile (According CTCAE, Version 4.0)</measure>
    <time_frame>Every week during the first month, week 6, week 9, week 12, every 4 weeks until end of treatment and at the end of treatment visit (28 days after the end of treatment), up to 36 months</time_frame>
    <description>The safety and tolerability of Pazopanib will be determined by means of type, incidence, severity, timing, seriousness, and relatedness; of reported adverse events (AEs), physical examinations, and laboratory tests. Toxicity will be graded and tabulated by the NCI-CTCAE v 4.0.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>Advanced and / or Metastatic Liposarcoma</condition>
  <arm_group>
    <arm_group_label>Pazopanib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pazopanib</intervention_name>
    <description>Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.</description>
    <arm_group_label>Pazopanib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 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;
             Informed consent must be obtained prior to start of the specified screening window.&#xD;
&#xD;
             Procedures conducted as part of the subject's routine clinical management (e.g., blood&#xD;
             count, imaging study such as bone scan) and obtained prior to signing of informed&#xD;
             consent may be utilized for screening or baseline purposes provided these procedures&#xD;
             are conducted as specified in the protocol.&#xD;
&#xD;
          2. Age ≥ 18 years or legal age of consent if greater than 18 years&#xD;
&#xD;
          3. Histological confirmed diagnosis of high or intermediate grade malignant liposarcoma&#xD;
             with metastatic or locally advanced disease. Formalin fixed paraffin embedded tumour&#xD;
             block and/or representative H/E (haematoxylin/eosin) slides must be available for&#xD;
             central pathologic review to classify tumors in the 2 eligible subtypes:&#xD;
&#xD;
             Well-differentiated liposarcoma/de-differentiated liposarcoma (ALT-WD) Myxoid/round&#xD;
             cell liposarcoma&#xD;
&#xD;
          4. Patient must have documentation of disease progression within 6 months prior to study&#xD;
             entry.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.&#xD;
&#xD;
          6. Measurable disease by RECIST v1.1 criteria. At least one measurable lesion located&#xD;
             outside of a previously irradiated area. If the only measurable lesion is in a&#xD;
             previously irradiated area, RECIST progression should be documented after&#xD;
             radiotherapy, in the previous 6 months before study entry.&#xD;
&#xD;
          7. The patient should not be considered eligible for surgery or radical radiotherapy.&#xD;
             e.g. Patients to whom surgery/radiotherapy can not be performed with a curative intent&#xD;
             due to the extension of the disease. In the case of radiotherapy, it may also be&#xD;
             limited due to a previous treatment with radiotherapy in the same area.&#xD;
&#xD;
          8. The patient must have either been considered ineligible for systemic chemotherapy or&#xD;
             received at least one previous regimen for relapsed, refractory or metastatic disease.&#xD;
             A maximum of three previous lines for advanced/metastatic disease are allowed.&#xD;
&#xD;
             Patients not eligible for systemic chemotherapy:&#xD;
&#xD;
             Because of age, a biological condition or patient-refusal Generally, patients that&#xD;
             received anthracyclines in the adjuvant setting are not eligible for first line&#xD;
             therapy with this agent for advanced disease.&#xD;
&#xD;
             Patients with a solitary kidney or &gt;60 years old are usually not the best candidates&#xD;
             for treatment with regular doses of ifosfamide.&#xD;
&#xD;
          9. Tumor tissue must be provided for all subjects for biomarker analysis before/during&#xD;
             treatment with investigational product.&#xD;
&#xD;
         10. The patient should be able to swallow and retain study drug&#xD;
&#xD;
         11. Adequate organ system function as defined:&#xD;
&#xD;
             Absolute neutrophil count (ANC)≥ 1.5 X 109/L Hemoglobin ≥ 9 g/dL (5.6 mmol/L)&#xD;
             Platelets ≥ 100 X 109/L Prothrombin time (PT) or international normalized ratio (INR)≤&#xD;
             1.2 X ULN Activated partial thromboplastin time (aPTT)≤ 1.2 X ULN Total bilirubin≤ 1.5&#xD;
             X ULN Alanine amino transferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5 X ULN&#xD;
             Serum creatinine ≤ 1.5 mg/dL (133 µmol/L)Or, if &gt;1.5 mg/dL: Calculated creatinine&#xD;
             clearance (ClCR)≥ 30 mL/min to ≥ 50 mL/min Urine Protein to Creatinine Ratio (UPC) &lt;1&#xD;
             Or, 24-hour urine protein &lt;1g&#xD;
&#xD;
               1. Subjects may not have had a transfusion within 7 days of screening assessment.&#xD;
&#xD;
               2. Subjects receiving anticoagulant therapy are eligible if their INR is stable and&#xD;
                  within the recommended range for the desired level of anticoagulation.&#xD;
&#xD;
               3. Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN (upper limit of&#xD;
                  normal) are not permitted.&#xD;
&#xD;
               4. If UPC ≥ 1, then a 24-hour urine protein must be assessed. Subjects must have a&#xD;
                  24-hour urine protein value &lt;1 g to be eligible. Use of urine dipstick for&#xD;
                  baseline renal function assessment is not acceptable.&#xD;
&#xD;
         12. A female is eligible to enter and participate in this study if she is of:&#xD;
&#xD;
             Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),&#xD;
             including any female who has had:&#xD;
&#xD;
             A hysterectomy A bilateral oophorectomy (ovariectomy) A bilateral tubal ligation Is&#xD;
             post-menopausal Female subjects not using hormone replacement therapy (HRT) must have&#xD;
             experienced total cessation of menses for ≥ 1 year and be greater than 45 years in&#xD;
             age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value &gt;40&#xD;
             mIU/mL and an estradiol value &lt; 40pg/mL (&lt;140 pmol/L).&#xD;
&#xD;
             Female subjects using HRT must have experienced total cessation of menses for ≥ 1 year&#xD;
             and be greater than 45 years of age OR have had documented evidence of menopause based&#xD;
             on FSH and estradiol concentrations prior to initiation of HRT&#xD;
&#xD;
             Childbearing potential, including any female who has had a negative serum pregnancy&#xD;
             test within 2 weeks prior to the first dose of study treatment, preferably as close to&#xD;
             the first dose as possible, and agrees to use adequate contraception. The acceptable&#xD;
             contraceptive methods, when used consistently and in accordance with both the product&#xD;
             label and the instructions of the physician, are as follows:&#xD;
&#xD;
             Complete abstinence from sexual intercourse for 14 days before exposure to&#xD;
             investigational product, through the dosing period, and for at least 21 days after the&#xD;
             last dose of investigational product Oral contraceptive, either combined or&#xD;
             progestogen alone Injectable progestogen Implants of levonorgestrel Estrogenic vaginal&#xD;
             ring Percutaneous contraceptive patches Intrauterine device (IUD) or intrauterine&#xD;
             system (IUS) with a documented failure rate of less than 1% per year Male partner&#xD;
             sterilization (vasectomy with documentation of azoospermia) prior to the female&#xD;
             subject's entry into the study, and this male is the sole partner for that subject&#xD;
             Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps)&#xD;
             with a vaginal spermicidal agent (foam/gel/film/cream/suppository) Female subjects who&#xD;
             are lactating should discontinue nursing prior to the first dose of study drug and&#xD;
             should refrain from nursing throughout the treatment period and for 14 days following&#xD;
             the last dose of study drug&#xD;
&#xD;
         13. LVEF above the lower limit of normal for the institution, based on ECHO or MUGA.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior history of malignancies other than liposarcoma. Subjects who have had another&#xD;
             malignancy and have been disease-free for 3 years, or subjects with a history of&#xD;
             completely resected non-melanomatous skin carcinoma or successfully treated in situ&#xD;
             carcinoma are eligible.&#xD;
&#xD;
          2. Clinical evidence of central nervous system (CNS) metastases or leptomeningeal&#xD;
             carcinomatosis, except for individuals who have previously-treated CNS metastases, are&#xD;
             asymptomatic, and have had no requirement for steroids or anti-seizure medication for&#xD;
             6 months prior to first dose of study drug. Screening with CNS imaging studies&#xD;
             (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if&#xD;
             clinically indicated or if the subject has a history of CNS metastases.&#xD;
&#xD;
          3. Clinically significant gastrointestinal abnormalities that may increase the risk for&#xD;
             gastrointestinal bleeding including, but not limited to:&#xD;
&#xD;
             Active peptic ulcer disease Known intraluminal metastatic lesion/s with risk of&#xD;
             bleeding Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or&#xD;
             other gastrointestinal conditions with increased risk of perforation History of&#xD;
             abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28&#xD;
             days prior to beginning study treatment.&#xD;
&#xD;
          4. Clinically significant gastrointestinal abnormalities that may affect absorption of&#xD;
             investigational product including, but not limited to:&#xD;
&#xD;
             Malabsorption syndrome Major resection of the stomach or small bowel.&#xD;
&#xD;
          5. Corrected QT interval (QTc) &gt; 480 msecs&#xD;
&#xD;
          6. History of any one or more of the following cardiovascular conditions within the past&#xD;
             6 months:&#xD;
&#xD;
             Cardiac angioplasty or stenting Myocardial infarction Unstable angina Coronary artery&#xD;
             bypass graft surgery Symptomatic peripheral vascular disease Class III or IV&#xD;
             congestive heart failure, as defined by the New York Heart Association (NYHA)&#xD;
&#xD;
          7. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg&#xD;
             or diastolic blood pressure (DBP) of ≥ 90mmHg].&#xD;
&#xD;
             Initiation or adjustment of antihypertensive medication(s) is permitted prior to study&#xD;
             entry. Following antihypertensive medication initiation or adjustment, blood pressure&#xD;
             (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24&#xD;
             hours must have elapsed between anti-hypertensive medication initiation or adjustment&#xD;
             and BP measurement. These three values should be averaged to obtain the mean diastolic&#xD;
             blood pressure and the mean systolic blood pressure. The mean SBP / DBP ratio must be&#xD;
             &lt;140/90 mmHg (OR 150/90 mm Hg, if this criterion is approved by Safety Review Team) in&#xD;
             order for a subject to be eligible for the study.&#xD;
&#xD;
          8. 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;
             Subjects with recent DVT who have been treated with therapeutic anti-coagulating&#xD;
             agents for at least 6 weeks are eligible&#xD;
&#xD;
          9. 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;
         10. Evidence of active bleeding or bleeding diathesis.&#xD;
&#xD;
         11. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that&#xD;
             increase the risk of pulmonary hemorrhage.&#xD;
&#xD;
             Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are&#xD;
             excluded; however, the presence of a tumor that is touching, but not infiltrating&#xD;
             (abutting) the vessels is acceptable (CT with contrast is strongly recommended to&#xD;
             evaluate such lesions).&#xD;
&#xD;
         12. Recent hemoptysis (≥ ½ teaspoon of red blood within 8 weeks before first dose of study&#xD;
             drug).&#xD;
&#xD;
         13. 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;
         14. Unable or unwilling to discontinue use of prohibited medications listed in section 7.4&#xD;
             of this protocol or at least 14 days or five half-lives of a drug (whichever is&#xD;
             longer) prior to the first dose of study drug and for the duration of the study.&#xD;
&#xD;
         15. Treatment with any of the following anti-cancer therapies:&#xD;
&#xD;
             radiation therapy, surgery or tumor embolization within 14 days prior to the first&#xD;
             dose of Pazopanib chemotherapy, immunotherapy, biologic therapy, investigational&#xD;
             therapy or 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;
         16. 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;
         17. 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>Claudia Valverde, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospitals de la Vall de Hebron</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bernd Kasper, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Centre Mannheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>HELIOS Klinikum Berlin-Buch (Sarkomzentrum Berlin-Brandenburg)</name>
      <address>
        <city>Berlin</city>
        <zip>D-10707</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum EssenInnere Klinik (Tumorforschung)</name>
      <address>
        <city>Essen</city>
        <zip>D-45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover (Zentrum Innere Medizin)</name>
      <address>
        <city>Hannover</city>
        <zip>D-30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsmedizin Mannheim (Sarkomzentrum)</name>
      <address>
        <city>Manheim</city>
        <zip>D-68169</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Großhadern der LMU Universität München (Med. Klinik und Poliklinik II)</name>
      <address>
        <city>Munich</city>
        <zip>D-80336</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Central de Asturias</name>
      <address>
        <city>Oviedo</city>
        <state>Asturias</state>
        <zip>33011</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Canarias</name>
      <address>
        <city>La Laguna</city>
        <state>Islas Canarias</state>
        <zip>38320</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Navarra</name>
      <address>
        <city>Pamplona</city>
        <state>Navarra</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario de Vigo</name>
      <address>
        <city>Vigo</city>
        <state>Pontevedra</state>
        <zip>36204</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Vall d'Hebrón</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Son Espases</name>
      <address>
        <city>Palma de Mallorca</city>
        <zip>07010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Valenciano de Oncología</name>
      <address>
        <city>Valencia</city>
        <zip>46009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Spain</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>September 14, 2012</study_first_submitted>
  <study_first_submitted_qc>September 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <results_first_submitted>June 2, 2020</results_first_submitted>
  <results_first_submitted_qc>July 8, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 23, 2020</results_first_posted>
  <last_update_submitted>July 8, 2020</last_update_submitted>
  <last_update_submitted_qc>July 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Advanced</keyword>
  <keyword>Metastatic</keyword>
  <keyword>Liposarcoma</keyword>
  <keyword>Pazopanib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liposarcoma</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 11, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT01692496/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 29, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT01692496/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>From 2013 to 2018, advanced and/or metastatic liposarcoma patients were recruited across 12 centres from Spain and Germany.</recruitment_details>
      <pre_assignment_details>Patients were clustered in two cohorts based on the liposarcoma type:&#xD;
Cohort A: well differentiated liposarcoma&#xD;
Cohort B: Myxoid/round cell liposarcoma&#xD;
Both cohorts were included in the single arm treatment: Pazopanib</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Pazopanib</title>
          <description>Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.&#xD;
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>3 Weeks Pazopanib (Per Protocol PP)</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="52"/>
              </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>Pazopanib</title>
          <description>Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.&#xD;
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="52"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.3" spread="13.5"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Germany</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="168.1" spread="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body weight</title>
          <units>Kg</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="77.3" spread="14.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Systolic pressure</title>
          <units>mm Hg</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="132.5" spread="15.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diastolic pressure</title>
          <units>mm Hg</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="78.8" spread="8.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression-free Survival (PFS) Assessed 12 Weeks After Start of Treatment</title>
        <description>The primary objective of this study is to evaluate the activity of Pazopanib in patients with advanced and/or metastatic liposarcoma by means of progression-free survival (PFS) assessed 12 weeks after start of treatment. (According the RECIST criteria 1.1 and central radiology review).&#xD;
Progression was defined according to RECIST criteria 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions</description>
        <time_frame>12 weeks after start of treatment</time_frame>
        <population>Per protocol population</population>
        <group_list>
          <group group_id="O1">
            <title>Pazopanib</title>
            <description>Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.&#xD;
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS) Assessed 12 Weeks After Start of Treatment</title>
          <description>The primary objective of this study is to evaluate the activity of Pazopanib in patients with advanced and/or metastatic liposarcoma by means of progression-free survival (PFS) assessed 12 weeks after start of treatment. (According the RECIST criteria 1.1 and central radiology review).&#xD;
Progression was defined according to RECIST criteria 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions</description>
          <population>Per protocol population</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="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cohort A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.1" lower_limit="38" upper_limit="70.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cohort B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.2" lower_limit="19.1" upper_limit="73.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Progression Free Survival (Median PFS)</title>
        <description>Overall progression free survival will be computed from the date of start of treatment to the first documented date of progression or the date of death, whatever the cause. Patients alive and free from progression at the time of the analysis will be censored at the date of last follow-up.</description>
        <time_frame>Imaging studies repeated every 6 weeks for the first 12 weeks and every 8 weeks up to 36 months.</time_frame>
        <population>Per protocol</population>
        <group_list>
          <group group_id="O1">
            <title>Pazopanib</title>
            <description>Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.&#xD;
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Progression Free Survival (Median PFS)</title>
          <description>Overall progression free survival will be computed from the date of start of treatment to the first documented date of progression or the date of death, whatever the cause. Patients alive and free from progression at the time of the analysis will be censored at the date of last follow-up.</description>
          <population>Per protocol</population>
          <units>Weeks</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="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pazopanib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.14" lower_limit="7.75" upper_limit="16.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cohort A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15" lower_limit="8.19" upper_limit="21.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cohort B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.29" lower_limit="5.09" upper_limit="15.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With Objective Tumor Response (OR)</title>
        <description>Objective tumor response, measured according to the RECIST 1.1 criteria (central reviewing) at 6 and 12 weeks.&#xD;
Response criteria are essentially based on a set of measurable lesions identified at baseline as target lesions, and followed until disease progression.&#xD;
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
        <time_frame>6 weeks and 12 weeks</time_frame>
        <population>Per protocol (PP)</population>
        <group_list>
          <group group_id="O1">
            <title>Pazopanib</title>
            <description>Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.&#xD;
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With Objective Tumor Response (OR)</title>
          <description>Objective tumor response, measured according to the RECIST 1.1 criteria (central reviewing) at 6 and 12 weeks.&#xD;
Response criteria are essentially based on a set of measurable lesions identified at baseline as target lesions, and followed until disease progression.&#xD;
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
          <population>Per protocol (PP)</population>
          <units>Percentage of patients</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="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>6 weeks OR (PP population)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8" lower_limit="0.5" upper_limit="15.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 weeks OR (PP population)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="1.4" upper_limit="9.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>It will be computed from the date of start of treatment to the date of death, whatever the cause. Patients alive or lost for follow-up at the time of the analysis will be censored at the date of last follow-up.</description>
        <time_frame>Every 12 weeks from disease progression up to 36 months.</time_frame>
        <population>Per protocol</population>
        <group_list>
          <group group_id="O1">
            <title>Pazopanib</title>
            <description>Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.&#xD;
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>It will be computed from the date of start of treatment to the date of death, whatever the cause. Patients alive or lost for follow-up at the time of the analysis will be censored at the date of last follow-up.</description>
          <population>Per protocol</population>
          <units>Weeks</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="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pazopanib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.43" lower_limit="44.92" upper_limit="95.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cohort A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.43" lower_limit="42.69" upper_limit="98.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cohort B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.29" lower_limit="31.21" upper_limit="111.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Rate</title>
        <description>Patients who achieve complete response (CR), partial response (PR), or stable disease (SD) for 6 months or more and an improvement of symptoms will be considered as having derived clinical benefit.</description>
        <time_frame>Imaging studies required to investigate known disease should be repeated every 6 weeks for the first 12 weeks and every 8 weeks up to 36 months.</time_frame>
        <population>Per population</population>
        <group_list>
          <group group_id="O1">
            <title>Pazopanib</title>
            <description>Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.&#xD;
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate</title>
          <description>Patients who achieve complete response (CR), partial response (PR), or stable disease (SD) for 6 months or more and an improvement of symptoms will be considered as having derived clinical benefit.</description>
          <population>Per population</population>
          <units>Percentage of patients</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="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pazopanib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26" lower_limit="13.8" upper_limit="38.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cohort A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.4" lower_limit="17.3" upper_limit="47.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cohort B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.7" lower_limit="6.8" upper_limit="22.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Growth Modulation Index (GMI)</title>
        <description>GMI is the ratio between time to progression (TTP) with pazopanib (TTPp) divided by the TTPp-1 with the previous line of therapy.&#xD;
GMI index values higher than 1 indicate that Pazopanib treatment has an increased time to progression when compared to previous line of treatment.&#xD;
GMI index values lower than 1 indicate that Pazopanib treatment has a reduced time to progression when compared to previous line of treatment.&#xD;
Higher GMI values are associated to a better outcome.</description>
        <time_frame>Imaging studies required to investigate known disease should be repeated every 6 weeks for the first 12 weeks and every 8 weeks up to 36 months. At patient progression confirmed by means RECIST criteria V 1.1</time_frame>
        <population>Per protocol with TTP and TTPp registered</population>
        <group_list>
          <group group_id="O1">
            <title>Pazopanib</title>
            <description>Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.&#xD;
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.</description>
          </group>
        </group_list>
        <measure>
          <title>Growth Modulation Index (GMI)</title>
          <description>GMI is the ratio between time to progression (TTP) with pazopanib (TTPp) divided by the TTPp-1 with the previous line of therapy.&#xD;
GMI index values higher than 1 indicate that Pazopanib treatment has an increased time to progression when compared to previous line of treatment.&#xD;
GMI index values lower than 1 indicate that Pazopanib treatment has a reduced time to progression when compared to previous line of treatment.&#xD;
Higher GMI values are associated to a better outcome.</description>
          <population>Per protocol with TTP and TTPp registered</population>
          <units>Arbitrary units</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="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pazopanib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" lower_limit="0.1" upper_limit="18.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cohort A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" lower_limit="0.1" upper_limit="18.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cohort B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" lower_limit="0.1" upper_limit="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety Profile (According CTCAE, Version 4.0)</title>
        <description>The safety and tolerability of Pazopanib will be determined by means of type, incidence, severity, timing, seriousness, and relatedness; of reported adverse events (AEs), physical examinations, and laboratory tests. Toxicity will be graded and tabulated by the NCI-CTCAE v 4.0.</description>
        <time_frame>Every week during the first month, week 6, week 9, week 12, every 4 weeks until end of treatment and at the end of treatment visit (28 days after the end of treatment), up to 36 months</time_frame>
        <population>Intention to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Pazopanib</title>
            <description>Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.&#xD;
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety Profile (According CTCAE, Version 4.0)</title>
          <description>The safety and tolerability of Pazopanib will be determined by means of type, incidence, severity, timing, seriousness, and relatedness; of reported adverse events (AEs), physical examinations, and laboratory tests. Toxicity will be graded and tabulated by the NCI-CTCAE v 4.0.</description>
          <population>Intention to treat</population>
          <units>Patients</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs Pazopanib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AEs Cohort A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AEs Cohort B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>related AEs Pazpanib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>related AEs Cohort A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>related AEs Cohort B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE grade ≥3 Pazopanib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE grade ≥3 Cohort A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE grade ≥3 Cohort B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>related-AE grade ≥3 Pazopanib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>related-AE grade ≥3 Cohort A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>related-AE grade ≥3 Cohort B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>prior to treatment AE Pazopanib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>prior to treatment AE Cohort A</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>prior to treatment AE Cohort B</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs up to 30 days after administration of the last dose of study drug, approximately 36 months</time_frame>
      <desc>Additionally to AEs and SAEs definitions, an abnormal objective test finding should be reported as an AE as follows:&#xD;
test result associated with clinically significant symptoms&#xD;
test result lead to a change in study dosing or discontinuation from the study, significant additional concomitant drug treatment or other therapy&#xD;
test result leads to any of the outcomes included in the definition of a SAE&#xD;
test result were considered to be an AE by the investigator</desc>
      <group_list>
        <group group_id="E1">
          <title>Pazopanib</title>
          <description>Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.&#xD;
Pazopanib: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.</description>
        </group>
      </group_list>
      <serious_events>
        <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="35" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>ALT increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Bilirrubin increase</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac dysrhythmia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Cardiac disorders</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal bleeding</sub_title>
                <description>Fatal</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>General status deterioration</sub_title>
                <description>Fatal</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Uncontrolled pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Femure fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Abscess of tumor mass</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Tumor progression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
              <event>
                <sub_title>Tumor debulking</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="52" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Adverse Events</sub_title>
                <description>52 patients presented adverse events, the list of adverse events by type was not further analysed.</description>
                <counts group_id="E1" subjects_affected="52" subjects_at_risk="52"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Trial Coordinating Investigator</name_or_title>
      <organization>GEIS</organization>
      <phone>912866807</phone>
      <email>secretaria@grupogeis.org</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/NCT01692496
org study id: GEIS-30
secondary id: 2012-002745-38
nct id: NCT01692496
lead sponsor: 
collaborator: 
has dmc: No
Soft tissue and bone sarcomas are rare malignant tumors, which encompasses a large family of
      more than 50 histologically distinct tumor subtypes, all of which share a putative
      mesenchymal origin. In the case of soft tissue sarcomas (STS) surgical excision is the
      mainstay of treatment, but despite curative surgery, around half of patients develop distant
      metastases and die from disease. Few therapeutic approaches are currently available to
      patients with unresectable, locally advanced, or metastatic STS and only anthracyclines,
      ifosfamide and trabectedin have shown activity, with response rates of 20-40% in previously
      untreated patients. Recent and ongoing trials have investigated a variety of combination
      chemotherapeutic regimens (variously employing ifosfamide, doxorubicin, gemcitabine,
      temozolomide, vincristine, cisplatin, and dacarbazine, among others) as well as targeted
      therapies, which in some cases have yielded improvements in response rate but which have had
      little impact on survival. No other medical option is currently available, and the median
      survival of patients with soft-tissue sarcoma with non-resectable metastases is around 12-15
      months, and approximately 8 months after second line chemotherapy.

      Liposarcomas are STS which account for at least 20% of all STS in adults. They can be further
      classified into 3 histologically and biologically different subtypes: well-differentiated
      liposarcoma/dedifferentiated liposarcoma (ALT-WD), myxoid or round cell liposarcoma and
      pleomorphic liposarcoma.

      ALT-WD liposarcomas are locally aggressive rarely metastasizing tumors characterized by ring
      or giant marker chromosomes on the cytogenetic analysis and by amplification of the 12q13-21
      region on Fluorescence In Situ Hybridization (FISH) (MDM2, CDK4 and HMGIC). They account for
      about 40% iv of liposarcomas with a 5 year Overall survival (OS) around 80%. In a series of
      WD/DD treated with several regimens response rate was 12.5% OS 15 months and median PFS 3.6
      months(95 confidence interval (CI): 3.3-5.9) Mixoid /round cell liposarcoma accounts for
      45-50% of all liposarcomas. They tend to metastasize to unusual soft tissue and bone
      locations. High histologic grade with more than 5% of round cell component is associated with
      a 5-year OS of 50% approximately. They are characterized by t(23;16)(q13-14;p11) which leads
      to the fusion of CHOP and TLS genes Pleomorphic liposarcoma accounts for approximately 5-10%
      of all liposarcomas, characterized by high grade features with frequent and early lung
      metastasis and cytogenetically by high chromosome counts and complex structural
      rearrangements.

      VEGF is expressed in many STS in which increased expression is associated with higher grade
      and worse prognosis.

      Pazopanib is an oral angiogenesis inhibitor that targets mainly VEGFR, PDGFR and c-kit.
      Recently the results of a phase II trial of pazopanib in STS have been published. It was a
      four-cohort 2-stages study. The liposarcoma stratum was closed after the first stage because
      of a PFS at 12 weeks of 17% (3 out of 17 patients did not progressed after 12 weeks). After
      central pathologic review, 2 other patients initially classified as other STS were found to
      have liposarcoma with stable disease at 12 weeks (5/19: 26% PFS12w), thus fulfilling criteria
      for cohort expansion. Phase II study had been completed and in phase III study patients with
      liposarcomas were excluded so therefore data on the liposarcoma cohort are inconclusive.

      Furthermore the positive results of the phase III study PALETTE have been recently
      communicated, encouraging this treatment in other sarcomas: progression-free survival (PFS)
      per independent review was significantly prolonged with pazopanib (median: 4.6 vs 1.5 months;
      HR=0.31, 95% CI 0.24-0.40; P<0.0001). The interim analysis for overall survival shows a
      statistically non-significant improvement of pazopanib vs placebo (median: 11.9 vs 10.4
      months, HR=0.83, 95% CI 0.62-1.09).

      Soluble factors associated with efficacy and toxicity of pazopanib in these patients had been
      also reported. Decreases in VEGFR2 and increase in PlGF were both associated with toxicity
      (HTA and TSH elevation) and poorer prognosis.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free Survival (PFS) Assessed 12 Weeks After Start of Treatment
time frame: 12 weeks after start of treatment
description: The primary objective of this study is to evaluate the activity of Pazopanib in patients with advanced and/or metastatic liposarcoma by means of progression-free survival (PFS) assessed 12 weeks after start of treatment. (According the RECIST criteria 1.1 and central radiology review).
Progression was defined according to RECIST criteria 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
measure: Overall Progression Free Survival (Median PFS)
time frame: Imaging studies repeated every 6 weeks for the first 12 weeks and every 8 weeks up to 36 months.
description: Overall progression free survival will be computed from the date of start of treatment to the first documented date of progression or the date of death, whatever the cause. Patients alive and free from progression at the time of the analysis will be censored at the date of last follow-up.
measure: Percentage of Patients With Objective Tumor Response (OR)
time frame: 6 weeks and 12 weeks
description: Objective tumor response, measured according to the RECIST 1.1 criteria (central reviewing) at 6 and 12 weeks.
Response criteria are essentially based on a set of measurable lesions identified at baseline as target lesions, and followed until disease progression.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
measure: Overall Survival (OS)
time frame: Every 12 weeks from disease progression up to 36 months.
description: It will be computed from the date of start of treatment to the date of death, whatever the cause. Patients alive or lost for follow-up at the time of the analysis will be censored at the date of last follow-up.
measure: Clinical Benefit Rate
time frame: Imaging studies required to investigate known disease should be repeated every 6 weeks for the first 12 weeks and every 8 weeks up to 36 months.
description: Patients who achieve complete response (CR), partial response (PR), or stable disease (SD) for 6 months or more and an improvement of symptoms will be considered as having derived clinical benefit.
measure: Growth Modulation Index (GMI)
time frame: Imaging studies required to investigate known disease should be repeated every 6 weeks for the first 12 weeks and every 8 weeks up to 36 months. At patient progression confirmed by means RECIST criteria V 1.1
description: GMI is the ratio between time to progression (TTP) with pazopanib (TTPp) divided by the TTPp-1 with the previous line of therapy.
GMI index values higher than 1 indicate that Pazopanib treatment has an increased time to progression when compared to previous line of treatment.
GMI index values lower than 1 indicate that Pazopanib treatment has a reduced time to progression when compared to previous line of treatment.
Higher GMI values are associated to a better outcome.
measure: Safety Profile (According CTCAE, Version 4.0)
time frame: Every week during the first month, week 6, week 9, week 12, every 4 weeks until end of treatment and at the end of treatment visit (28 days after the end of treatment), up to 36 months
description: The safety and tolerability of Pazopanib will be determined by means of type, incidence, severity, timing, seriousness, and relatedness; of reported adverse events (AEs), physical examinations, and laboratory tests. Toxicity will be graded and tabulated by the NCI-CTCAE v 4.0.
arm group label: Pazopanib
arm group type: Experimental
description: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
intervention type: Drug
intervention name: Pazopanib
description: Patients will receive oral pazopanib, 800mg once daily and treatment will continue until disease progression, development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient or investigator decision.
arm group label: Pazopanib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Claudia Valverde, MD
role: Study Chair
affiliation: Hospitals de la Vall de Hebron
last name: Bernd Kasper, MD
role: Principal Investigator
affiliation: University Medical Centre Mannheim
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country: Germany
country: Spain
responsible party type: Sponsor
mesh term: Liposarcoma
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