<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/NCT02247544</url>
  </required_header>
  <id_info>
    <org_study_id>ISG-STS-TRAB-2012</org_study_id>
    <secondary_id>2012-005428-14</secondary_id>
    <nct_id>NCT02247544</nct_id>
  </id_info>
  <brief_title>Efficacy Study on Trabectedin in Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma</brief_title>
  <acronym>TRAVELL</acronym>
  <official_title>A Phase II Study on Trabectedin in Advanced Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Italian Sarcoma Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Istituto Di Ricerche Farmacologiche Mario Negri</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Italian Sarcoma Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an Italian, multicentre, single arm, phase II study, with an intra-patient comparison&#xD;
      end point. This study aims at confirming the activity of the drug trabectedin as&#xD;
      second/further line treatment in retroperitoneal leiomyosarcoma and well&#xD;
      differentiated/dedifferentiated liposarcoma expressed in terms of slowing down tumour growth.&#xD;
&#xD;
      Another objective is to investigate this peculiar benefit of trabectedin in typical&#xD;
      retroperitoneal sarcomas may be exploited to help multidisciplinary clinical decision-making&#xD;
      in the management of retroperitoneal sarcomas&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Retroperitoneal soft-tissue sarcomas (R-STSs) are rare neoplasms, accounting for 10% to 15%&#xD;
      of Soft Tissue Sarcomas (STSs), which represent 1-3% of all cancers. They may show different&#xD;
      histological types, but the predominant ones in the retroperitoneal region are:&#xD;
      leiomyosarcoma, liposarcoma. The most commonly encountered in the retroperitoneum is the well&#xD;
      differentiated/dedifferentiated liposarcoma.&#xD;
&#xD;
      First-line chemotherapy usually consists of doxorubicin and/or ifosfamide. These two drugs&#xD;
      are the most active agents in adult STSs, with a dose-response relationship and response&#xD;
      rates between 20% and 50%. However, the sarcoma community is currently doubtful as to the&#xD;
      activity of ifosfamide in the subgroup of leiomyosarcomas.&#xD;
&#xD;
      Trabectedin has been found to be mainly active in leiomyosarcoma and liposarcoma and is&#xD;
      approved by European Medicines Agency (EMA) as second-line chemotherapy for STSs. Although&#xD;
      the response rate observed in pre-registration studies did not exceed 10%, trabectedin&#xD;
      provided disease control, with progression arrest rates exceeding 50% and Progression Free&#xD;
      Survival (PFS) rates exceeding 20% at 6 months.&#xD;
&#xD;
      Since so far no phase II studies tested the activity of trabectedin in retroperitoneal&#xD;
      sarcomas, this is the specific aim of this study.&#xD;
&#xD;
      Target population: Patients with previously treated, histologically confirmed,&#xD;
      retroperitoneal leiomyosarcoma and well differentiated/dedifferentiated liposarcoma. Patients&#xD;
      may be either unamenable to surgery or amenable but in whom the addition of medical treatment&#xD;
      is considered clinically advisable.&#xD;
&#xD;
      Translational studies will be performed, with the aim of characterising the tumour biological&#xD;
      features associated with different response patterns to trabectedin. These assessments will&#xD;
      be done in 15-20 patients who will undergo surgery after trabectedin, comparing tumour tissue&#xD;
      specimens collected before and after treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2014</start_date>
  <completion_date type="Actual">March 12, 2019</completion_date>
  <primary_completion_date type="Actual">March 12, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Growth Modulation Rate</measure>
    <time_frame>From date of randomization until progressive disease, assessed up to 48 months</time_frame>
    <description>The primary end point of the study will be the proportion of responders to trabectedin, based on the ratio, in each single patient, between PFS under trabectedin (PFS) and time to progression after previous chemotherapy treatment (TTP1).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response (OR) in the overall sample</measure>
    <time_frame>From date of randomization until progressive disease, assessed up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathological tumour response in the two eligible histological types, in patients undergoing surgery after treatment</measure>
    <time_frame>From date of randomization until the best tumour dimensional response, assessed up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS and OR in the two eligible histological types</measure>
    <time_frame>From date of randomization until progressive disease, assessed up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS in patients who undergo surgery after, or during, medical therapy and those who do not</measure>
    <time_frame>From date of randomization until progressive disease, assessed up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with grade&gt;=3 adverse drug reactions, number of serious adverse events related to study drug and number of patients who will experience at least one serious adverse event</measure>
    <time_frame>From date of randomization until progressive disease, assessed up to 48 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of trabectedin in reducing cancer related pain</measure>
    <time_frame>From date of randomization until progressive disease, assessed up to 48 months</time_frame>
    <description>All patients will be administered a standardized questionnaire evaluating cancer related pain and use of antalgic medication.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">105</enrollment>
  <condition>Liposarcoma</condition>
  <condition>Leiomyosarcoma</condition>
  <arm_group>
    <arm_group_label>Trabectedin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trabectedin will be administered intravenously at a dose of 1.5 mg/m2 or 1.3 mg/m2 (at investigator's discretion, with a top-dose of 2.6 total mg per cycle) as a 24-hour infusion once every 3 weeks (cycle day 1).&#xD;
Since trabectedin has no cumulative toxicities, treatment can be continued until progressive disease, major toxicity, patient's intolerance or unwillingness to continue treatment or medical decision by the responsible physician. In the subgroup of patients amenable to surgery, treatment will be reasonably continued until the best dimensional response.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trabectedin</intervention_name>
    <description>Trabectedin administered at a dose of 1.5 mg/m2 - 1.3 mg/m2 (at investigator's discretion, with a top-dose of 2.6 total mg per cycle) as a 24-hour continuous infusion via a central venous access until progressive disease, major toxicity, patient's intolerance, unwillingness to continue treatment, or medical decision by the responsible physician</description>
    <arm_group_label>Trabectedin</arm_group_label>
    <other_name>Yondelis</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Persistent or locally relapsed and/or metastatic disease (in case of local disease,&#xD;
             surgery may be technically feasible or not, but the clinical judgment must be that&#xD;
             medical therapy is indicated)&#xD;
&#xD;
          -  Pathology specimens available for centralized review&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  European Eastern Cooperative Oncology Group Personal Status (ECOG PS) ≤ 2&#xD;
&#xD;
          -  One or more previous systemic treatments employing anthracyclines and ifosfamide&#xD;
             (unless one or both are clinically contraindicated)&#xD;
&#xD;
          -  Measurable disease, as defined by Response Evaluation Criteria In Solid Tumors&#xD;
             (RECIST)&#xD;
&#xD;
          -  A minimum of 3 weeks since any previous medical therapy&#xD;
&#xD;
          -  Recovery from toxic effects of prior therapies to National Cancer Institute Common&#xD;
             Toxicity Criteria (NCI CTC) Grade 1 or lower&#xD;
&#xD;
          -  Adequate haematological, renal and liver functions&#xD;
&#xD;
          -  Ability and willingness to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breast-feeding women&#xD;
&#xD;
          -  Prior exposure to trabectedin&#xD;
&#xD;
          -  Peripheral neuropathy, Grade 2 or higher&#xD;
&#xD;
          -  History of other malignancies (except for basal cell carcinoma or cervical carcinoma&#xD;
             in situ, adequately treated), unless in remission for 5 years or more and judged of&#xD;
             negligible potential of relapse&#xD;
&#xD;
          -  Known central nervous system (CNS) metastases&#xD;
&#xD;
          -  Active viral hepatitis or chronic liver disease&#xD;
&#xD;
          -  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;
          -  Active major infection&#xD;
&#xD;
          -  Other serious concomitant illnesses&#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>Paolo G. Casali, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>IRCCS Fondazione Istituto Nazionale per la cura dei tumori di Milano</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Istituto Tumori Giovanni Paolo II</name>
      <address>
        <city>Bari</city>
        <state>BA</state>
        <zip>70124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Giovanni Paolo XXIII</name>
      <address>
        <city>Bergamo</city>
        <state>BG</state>
        <zip>24127</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera S. Orsola-Malpighi</name>
      <address>
        <city>Bologna</city>
        <state>BO</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Spedali Civili</name>
      <address>
        <city>Brescia</city>
        <state>BS</state>
        <zip>25123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Oncologico A. Businco</name>
      <address>
        <city>Cagliari</city>
        <state>CA</state>
        <zip>09122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera S Croce e Carle</name>
      <address>
        <city>Cuneo</city>
        <state>CN</state>
        <zip>12100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Sant'Anna</name>
      <address>
        <city>Como</city>
        <state>CO</state>
        <zip>22020</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRST IRCCS Meldola</name>
      <address>
        <city>Meldola</city>
        <state>FC</state>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Nazionale dei Tumori</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas</name>
      <address>
        <city>Rozzano</city>
        <state>MI</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Paolo Giaccone</name>
      <address>
        <city>Palermo</city>
        <state>PA</state>
        <zip>90127</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro di Riferimento Oncologico di Aviano</name>
      <address>
        <city>Aviano</city>
        <state>PD</state>
        <zip>33081</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Oncologico Veneto</name>
      <address>
        <city>Padova</city>
        <state>PD</state>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Santa Chiara</name>
      <address>
        <city>Pisa</city>
        <state>PI</state>
        <zip>56124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Misericordia e Dolce</name>
      <address>
        <city>Prato</city>
        <state>PO</state>
        <zip>59100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Universitario Campus Biomedico</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto per la Ricerca e la Cura del Cancro di Candiolo</name>
      <address>
        <city>Candiolo</city>
        <state>TO</state>
        <zip>10060</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Gradenigo</name>
      <address>
        <city>Torino</city>
        <state>TO</state>
        <zip>10153</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Santa Maria</name>
      <address>
        <city>Terni</city>
        <state>TR</state>
        <zip>05100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori - IRCCS - Fondazione Pascale</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <link>
    <url>http://medicine.iupui.edu/flockhart/table.htm</url>
    <description>On this website page physicians can find the complete list of Cytochrome P450 3A4 (CYP3A4) enzyme inducers/inhibitors which may alter the plasma concentrations of the trabectedin</description>
  </link>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>September 5, 2014</study_first_submitted>
  <study_first_submitted_qc>September 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>October 29, 2021</last_update_submitted>
  <last_update_submitted_qc>October 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>STS, leiomyosarcoma, liposarcoma, trabectedin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leiomyosarcoma</mesh_term>
    <mesh_term>Liposarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT02247544
org study id: ISG-STS-TRAB-2012
secondary id: 2012-005428-14
nct id: NCT02247544
lead sponsor: 
collaborator: 
has dmc: No
This is an Italian, multicentre, single arm, phase II study, with an intra-patient comparison
      end point. This study aims at confirming the activity of the drug trabectedin as
      second/further line treatment in retroperitoneal leiomyosarcoma and well
      differentiated/dedifferentiated liposarcoma expressed in terms of slowing down tumour growth.

      Another objective is to investigate this peculiar benefit of trabectedin in typical
      retroperitoneal sarcomas may be exploited to help multidisciplinary clinical decision-making
      in the management of retroperitoneal sarcomas
Retroperitoneal soft-tissue sarcomas (R-STSs) are rare neoplasms, accounting for 10% to 15%
      of Soft Tissue Sarcomas (STSs), which represent 1-3% of all cancers. They may show different
      histological types, but the predominant ones in the retroperitoneal region are:
      leiomyosarcoma, liposarcoma. The most commonly encountered in the retroperitoneum is the well
      differentiated/dedifferentiated liposarcoma.

      First-line chemotherapy usually consists of doxorubicin and/or ifosfamide. These two drugs
      are the most active agents in adult STSs, with a dose-response relationship and response
      rates between 20% and 50%. However, the sarcoma community is currently doubtful as to the
      activity of ifosfamide in the subgroup of leiomyosarcomas.

      Trabectedin has been found to be mainly active in leiomyosarcoma and liposarcoma and is
      approved by European Medicines Agency (EMA) as second-line chemotherapy for STSs. Although
      the response rate observed in pre-registration studies did not exceed 10%, trabectedin
      provided disease control, with progression arrest rates exceeding 50% and Progression Free
      Survival (PFS) rates exceeding 20% at 6 months.

      Since so far no phase II studies tested the activity of trabectedin in retroperitoneal
      sarcomas, this is the specific aim of this study.

      Target population: Patients with previously treated, histologically confirmed,
      retroperitoneal leiomyosarcoma and well differentiated/dedifferentiated liposarcoma. Patients
      may be either unamenable to surgery or amenable but in whom the addition of medical treatment
      is considered clinically advisable.

      Translational studies will be performed, with the aim of characterising the tumour biological
      features associated with different response patterns to trabectedin. These assessments will
      be done in 15-20 patients who will undergo surgery after trabectedin, comparing tumour tissue
      specimens collected before and after treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Growth Modulation Rate
time frame: From date of randomization until progressive disease, assessed up to 48 months
description: The primary end point of the study will be the proportion of responders to trabectedin, based on the ratio, in each single patient, between PFS under trabectedin (PFS) and time to progression after previous chemotherapy treatment (TTP1).
measure: Objective response (OR) in the overall sample
time frame: From date of randomization until progressive disease, assessed up to 48 months
measure: Pathological tumour response in the two eligible histological types, in patients undergoing surgery after treatment
time frame: From date of randomization until the best tumour dimensional response, assessed up to 48 months
measure: PFS and OR in the two eligible histological types
time frame: From date of randomization until progressive disease, assessed up to 48 months
measure: PFS in patients who undergo surgery after, or during, medical therapy and those who do not
time frame: From date of randomization until progressive disease, assessed up to 48 months
measure: Number of patients with grade>=3 adverse drug reactions, number of serious adverse events related to study drug and number of patients who will experience at least one serious adverse event
time frame: From date of randomization until progressive disease, assessed up to 48 months
measure: Efficacy of trabectedin in reducing cancer related pain
time frame: From date of randomization until progressive disease, assessed up to 48 months
description: All patients will be administered a standardized questionnaire evaluating cancer related pain and use of antalgic medication.
arm group label: Trabectedin
arm group type: Experimental
description: Trabectedin will be administered intravenously at a dose of 1.5 mg/m2 or 1.3 mg/m2 (at investigator's discretion, with a top-dose of 2.6 total mg per cycle) as a 24-hour infusion once every 3 weeks (cycle day 1).
Since trabectedin has no cumulative toxicities, treatment can be continued until progressive disease, major toxicity, patient's intolerance or unwillingness to continue treatment or medical decision by the responsible physician. In the subgroup of patients amenable to surgery, treatment will be reasonably continued until the best dimensional response.
intervention type: Drug
intervention name: Trabectedin
description: Trabectedin administered at a dose of 1.5 mg/m2 - 1.3 mg/m2 (at investigator's discretion, with a top-dose of 2.6 total mg per cycle) as a 24-hour continuous infusion via a central venous access until progressive disease, major toxicity, patient's intolerance, unwillingness to continue treatment, or medical decision by the responsible physician
arm group label: Trabectedin
other name: Yondelis
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paolo G. Casali, MD
role: Principal Investigator
affiliation: IRCCS Fondazione Istituto Nazionale per la cura dei tumori di Milano
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Italy
url: http://medicine.iupui.edu/flockhart/table.htm
description: On this website page physicians can find the complete list of Cytochrome P450 3A4 (CYP3A4) enzyme inducers/inhibitors which may alter the plasma concentrations of the trabectedin
responsible party type: Sponsor
mesh term: Leiomyosarcoma
mesh term: Liposarcoma
mesh term: Trabectedin