<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/NCT02249702</url>
  </required_header>
  <id_info>
    <org_study_id>TAUL</org_study_id>
    <secondary_id>2009-016017-24</secondary_id>
    <nct_id>NCT02249702</nct_id>
  </id_info>
  <brief_title>Activity of Trabectedin or Gemcitabine + Docetaxel in Uterine Leiomyosarcoma</brief_title>
  <acronym>TAUL</acronym>
  <official_title>A Phase II Randomized - Non Comparative - Study on the Activity of Trabectedin or Gemcitabine + Docetaxel in Metastatic or Locally Relapsed Uterine Leiomyosarcoma Pretreated With Conventional Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mario Negri Institute for Pharmacological Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>PharmaMar</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Mario Negri Institute for Pharmacological Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The management of patients with uterine leiomyosarcomas poses many difficulties. Despite 60%&#xD;
      of women present with disease limited to the uterus, cure rates range from 20 to 60%.&#xD;
      Patients with metastatic disease at diagnosis or who recur after initial treatment have a&#xD;
      dismal prognosis and, except for a subset of selected patients with completely resectable&#xD;
      disease, the median survival is less than one year. Treatment options for&#xD;
      recurrent/metastatic uterine leiomyosarcoma are limited. The most active drugs are&#xD;
      doxorubicin ± ifosfamide and gemcitabine + docetaxel (GD) with response rate of 25-55% and&#xD;
      27-53%, respectively. Both these regimens have been increasingly used in the last years also&#xD;
      in the adjuvant setting. For relapsed patients other drugs have been tested as single agent&#xD;
      but negligible activity was observed.&#xD;
&#xD;
      Trabectedin (Yondelis® -T) is a marine-derived cytotoxic approved by EMEA. It is indicated&#xD;
      for the treatment of patients with advanced soft tissue sarcoma, after failure of&#xD;
      anthracyclines and ifosfamide or who are unsuitable to receive these agents. Among STS,&#xD;
      activity has been mainly detected in synovial sarcoma, liposarcoma and leiomyosarcoma.&#xD;
      Although the response rate did not exceed 10%, T was demonstrated to provide disease control,&#xD;
      with progression arrest rates exceeding 50% and progression-free survival rates exceeding 20%&#xD;
      at 6 months. So far no phase II studies tested the activity of T in uterine leiomyosarcoma&#xD;
      specifically. This study is aimed at evaluating the activity of T (arm A) in advanced uterine&#xD;
      leiomyosarcomas, having GD (arm B) as an internal control In parallel translational studies&#xD;
      will be performed to identify factors predictive of the activity of T in this specific&#xD;
      histotype.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2010</start_date>
  <completion_date type="Actual">April 30, 2017</completion_date>
  <primary_completion_date type="Actual">April 30, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>progression free rate at 6-month</measure>
    <time_frame>6-month</time_frame>
    <description>Primary objective will be to assess the clinical benefit rate (defined as 6-month progression free rate) with trabectedin in patients with locally relapsed/metastatic uterine leiomyosarcoma pretreated with anthracycline ± ifosfamide and/or gemcitabine ± docetaxel.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>best response rate</measure>
    <time_frame>within 6 months</time_frame>
    <description>response rate according to RECIST v1.0 criteria</description>
  </secondary_outcome>
  <other_outcome>
    <measure>progression free survival</measure>
    <time_frame>24 months</time_frame>
    <description>Time from inclusion into the study to progression or death whichever comes first</description>
  </other_outcome>
  <other_outcome>
    <measure>Overall survival</measure>
    <time_frame>24 months</time_frame>
    <description>time from inclusion into the study to death from any cause</description>
  </other_outcome>
  <other_outcome>
    <measure>safety profile</measure>
    <time_frame>up to 30 days after the end of treatments</time_frame>
    <description>Number of Patients with Serious and Non-Serious Adverse Events</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">168</enrollment>
  <condition>Leiomyosarcoma</condition>
  <arm_group>
    <arm_group_label>Trabectedin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trabectedin 1.3 mg/m2 will be administered via a central venous catheter as a 24-hour infusion on day 1 of 21-days treatment cycles. Trabectedin treatment can be continued until progressive disease, major toxicity, patient's intolerance or unwillingness to continue treatment or medical decision by the responsible physician.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>gemcitabine + docetaxel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Gemcitabine 900 mg/m2 will be administered via a central venous catheter on days one and eight over 90 min, followed by docetaxel 75 mg/m2 on day eight iv over 1 h. Gemcitabine+docetaxel treatment is planned for six cycles, unless there is evidence of disease progression, unacceptable toxicity or patient's intolerance or unwillingness to continue treatment, or medical decision by the responsible physician. Patients with continued response after six cycles can receive two additional cycles of combination therapy or continue with Gemcitabine alone.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>gemcitabine + docetaxel</intervention_name>
    <arm_group_label>gemcitabine + docetaxel</arm_group_label>
    <other_name>Gemzar</other_name>
    <other_name>Taxotere</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>trabectedin</intervention_name>
    <arm_group_label>Trabectedin</arm_group_label>
    <other_name>Yondelis</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically proven uterine leiomyosarcoma.&#xD;
&#xD;
          2. Persistent or locally relapsed and/or metastatic disease.&#xD;
&#xD;
          3. At least one previous systemic treatment with an anthracycline ± ifosfamide or&#xD;
             gemcitabine ± docetaxel.&#xD;
&#xD;
          4. Measurable disease, as defined by RECIST criteria.&#xD;
&#xD;
          5. ECOG PS &lt;=2.&#xD;
&#xD;
          6. Age &gt;= 18 years.&#xD;
&#xD;
          7. A minimum of 3 weeks since prior tumor directed therapy&#xD;
&#xD;
          8. Recovery from toxic effects of prior therapies to NCI CTC Grade 1 or lower.&#xD;
&#xD;
          9. Adequate haematological function.&#xD;
&#xD;
         10. Adequate renal function.&#xD;
&#xD;
         11. Adequate liver function.&#xD;
&#xD;
         12. Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior exposure to Trabectedin.&#xD;
&#xD;
          2. Peripheral neuropathy, Grade 2 or higher.&#xD;
&#xD;
          3. History of other malignancies (except basal cell carcinoma or cervical carcinoma in&#xD;
             situ, adequately treated), unless in remission from 5 years or more and judged of&#xD;
             negligible potential of relapse.&#xD;
&#xD;
          4. Known CNS metastases.&#xD;
&#xD;
          5. Active viral hepatitis or chronic liver disease.&#xD;
&#xD;
          6. Unstable cardiac condition, including congestive heart failure or angina pectoris,&#xD;
             myocardial infarction within one year before enrolment, uncontrolled arterial&#xD;
             hypertension or arrhythmias.&#xD;
&#xD;
          7. Active major infection.&#xD;
&#xD;
          8. Other serious concomitant illnesses&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Angiolo Gadducci, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Azienda Ospedaliero Universitaria Pisana, Pisa, Italy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Federica Grosso, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Azienda Ospedaliera Alessandria, Italy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centro di Riferimento Oncologico</name>
      <address>
        <city>Aviano</city>
        <state>Pordenone</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Umberto I</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00186</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione del Piemonte per l'Oncologia</name>
      <address>
        <city>Candiolo</city>
        <state>Turin</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda ULSS 13 Regione Veneto, Ospedale di Mirano</name>
      <address>
        <city>Mirano</city>
        <state>Venice</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Sacro Cuore Don Calabria</name>
      <address>
        <city>Negrar</city>
        <state>Verona</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo</name>
      <address>
        <city>Alessandria</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Spedali Civili di Brescia</name>
      <address>
        <city>Brescia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Presidio Ospedaliero Senatore Antonio Perrino</name>
      <address>
        <city>Brindisi</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera per l'Emergenza Cannizzaro</name>
      <address>
        <city>Catania</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Sant'Anna</name>
      <address>
        <city>Como</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera S. Croce e Carle</name>
      <address>
        <city>Cuneo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria San Martino - IST</name>
      <address>
        <city>Genoa</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ente Ospedaliero Ospedali Galliera</name>
      <address>
        <city>Genova</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda USL 2 Toscana - Nuovo Ospedale San Luca</name>
      <address>
        <city>Lucca</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale dei Tumori di Milano</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Milan</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia</name>
      <address>
        <city>Milan</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale dei Tumori di Milano</name>
      <address>
        <city>Milan</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera San Gerardo</name>
      <address>
        <city>Monza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori - Fondazione Pascale</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Maggiore della Carità</name>
      <address>
        <city>Novara</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Oncologico Veneto</name>
      <address>
        <city>Padova</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello</name>
      <address>
        <city>Palermo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria di Parma</name>
      <address>
        <city>Parma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico San Matteo</name>
      <address>
        <city>Pavia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospadaliero-Universitaria Pisana</name>
      <address>
        <city>Pisa</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Regionale San Carlo</name>
      <address>
        <city>Potenza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Arcispedale S. Maria Nuova</name>
      <address>
        <city>Reggio Emilia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale San Giovanni Calibita Fatebenefratelli</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Umberto I - Università Sapienza</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinco Universitario Agostino Gemelli</name>
      <address>
        <city>Rome</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Ordine Mauriziano</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria di Torino - Presidio Sant'Anna</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Presidio Sanitario Gradenigo</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>September 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>December 5, 2017</last_update_submitted>
  <last_update_submitted_qc>December 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>trabectedin</keyword>
  <keyword>uterine leiomyosarcoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leiomyosarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Trabectedin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02249702
org study id: TAUL
secondary id: 2009-016017-24
nct id: NCT02249702
lead sponsor: 
collaborator: 
has dmc: No
The management of patients with uterine leiomyosarcomas poses many difficulties. Despite 60%
      of women present with disease limited to the uterus, cure rates range from 20 to 60%.
      Patients with metastatic disease at diagnosis or who recur after initial treatment have a
      dismal prognosis and, except for a subset of selected patients with completely resectable
      disease, the median survival is less than one year. Treatment options for
      recurrent/metastatic uterine leiomyosarcoma are limited. The most active drugs are
      doxorubicin ± ifosfamide and gemcitabine + docetaxel (GD) with response rate of 25-55% and
      27-53%, respectively. Both these regimens have been increasingly used in the last years also
      in the adjuvant setting. For relapsed patients other drugs have been tested as single agent
      but negligible activity was observed.

      Trabectedin (Yondelis® -T) is a marine-derived cytotoxic approved by EMEA. It is indicated
      for the treatment of patients with advanced soft tissue sarcoma, after failure of
      anthracyclines and ifosfamide or who are unsuitable to receive these agents. Among STS,
      activity has been mainly detected in synovial sarcoma, liposarcoma and leiomyosarcoma.
      Although the response rate did not exceed 10%, T was demonstrated to provide disease control,
      with progression arrest rates exceeding 50% and progression-free survival rates exceeding 20%
      at 6 months. So far no phase II studies tested the activity of T in uterine leiomyosarcoma
      specifically. This study is aimed at evaluating the activity of T (arm A) in advanced uterine
      leiomyosarcomas, having GD (arm B) as an internal control In parallel translational studies
      will be performed to identify factors predictive of the activity of T in this specific
      histotype.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: progression free rate at 6-month
time frame: 6-month
description: Primary objective will be to assess the clinical benefit rate (defined as 6-month progression free rate) with trabectedin in patients with locally relapsed/metastatic uterine leiomyosarcoma pretreated with anthracycline ± ifosfamide and/or gemcitabine ± docetaxel.
measure: best response rate
time frame: within 6 months
description: response rate according to RECIST v1.0 criteria
measure: progression free survival
time frame: 24 months
description: Time from inclusion into the study to progression or death whichever comes first
measure: Overall survival
time frame: 24 months
description: time from inclusion into the study to death from any cause
measure: safety profile
time frame: up to 30 days after the end of treatments
description: Number of Patients with Serious and Non-Serious Adverse Events
arm group label: Trabectedin
arm group type: Experimental
description: Trabectedin 1.3 mg/m2 will be administered via a central venous catheter as a 24-hour infusion on day 1 of 21-days treatment cycles. Trabectedin treatment can be continued until progressive disease, major toxicity, patient's intolerance or unwillingness to continue treatment or medical decision by the responsible physician.
arm group label: gemcitabine + docetaxel
arm group type: Active Comparator
description: Gemcitabine 900 mg/m2 will be administered via a central venous catheter on days one and eight over 90 min, followed by docetaxel 75 mg/m2 on day eight iv over 1 h. Gemcitabine+docetaxel treatment is planned for six cycles, unless there is evidence of disease progression, unacceptable toxicity or patient's intolerance or unwillingness to continue treatment, or medical decision by the responsible physician. Patients with continued response after six cycles can receive two additional cycles of combination therapy or continue with Gemcitabine alone.
intervention type: Drug
intervention name: gemcitabine + docetaxel
arm group label: gemcitabine + docetaxel
other name: Gemzar
other name: Taxotere
intervention type: Drug
intervention name: trabectedin
arm group label: Trabectedin
other name: Yondelis
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Angiolo Gadducci, MD
role: Principal Investigator
affiliation: Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
last name: Federica Grosso, MD
role: Principal Investigator
affiliation: Azienda Ospedaliera Alessandria, Italy
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Leiomyosarcoma
mesh term: Gemcitabine
mesh term: Docetaxel
mesh term: Trabectedin