<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/NCT02997358</url>
  </required_header>
  <id_info>
    <org_study_id>2016-002186-56</org_study_id>
    <secondary_id>2016/2410</secondary_id>
    <nct_id>NCT02997358</nct_id>
  </id_info>
  <brief_title>Study Comparing Efficacy of Doxorubicin With Trabectedin Followed by Trabectedin Versus Doxorubicine in Patients With Leiomyosarcoma</brief_title>
  <acronym>LMS04</acronym>
  <official_title>Randomised Phase III Multicentric Study Comparing Efficacy of Doxorubicin With Trabectedin Followed by Trabectedin in Non-progressive Patients Versus Doxorubicine Alone as First-line Therapy in Patients With Metastatic or Unresectable Leiomyosarcoma (Uterine or Soft Tissue)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gustave Roussy, Cancer Campus, Grand Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gustave Roussy, Cancer Campus, Grand Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of LMS04 study is to better define the treatment strategy for patients with&#xD;
      metastatic leiomyosarcoma (uterine or soft tissue), as well as identifying the best first&#xD;
      line therapeutic option for these patients. LMS04 will test a new strategy for first line&#xD;
      therapy LMS sarcoma compare to the reference therapy (6 cycles of doxorubicin alone): the&#xD;
      interest of the association of trabectedin to doxorubicin in first line treatment followed by&#xD;
      trabectedin alone for non-progressive patients after 6 cycles of the association of&#xD;
      trabectedin and doxorubicin (the LMS02 design).&#xD;
&#xD;
      LMS04 will be the first phase III randomized study specifically dedicated to soft tissue&#xD;
      leiomyosarcoma in first line metastatic disease.&#xD;
&#xD;
      It is planned to compare a new doxorubicin combination (including trabectedin) with very&#xD;
      encouraging results followed by trabectedin maintenance therapy for non-progressive patients&#xD;
      to doxorubicin alone. Prospective ancillary translational studies will attempt to define&#xD;
      profiles of patients who could benefit from this new chemotherapy in an exploratory way.&#xD;
&#xD;
      The validation of a new first line option specific for LMS, identifying clinical factors that&#xD;
      characterize aggressiveness and responsiveness to treatment aims to have an important in the&#xD;
      spirit of personalized medicine in this rare and deadly disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 18, 2017</start_date>
  <completion_date type="Actual">July 28, 2021</completion_date>
  <primary_completion_date type="Actual">July 28, 2021</primary_completion_date>
  <phase>Phase 3</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 Survival</measure>
    <time_frame>Until progression or 2 years after randomization, whichever occurs first</time_frame>
    <description>Tumour assessment will be analysed using RECIST 1.1 criteria.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Uterine or Soft Tissue Leiomyosarcoma</condition>
  <arm_group>
    <arm_group_label>Doxorubicin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>6 cycles - 1 cycle every 3 weeks (day 1 to day 21) On day 1: Doxorubicin 75 mg/m² IV</description>
  </arm_group>
  <arm_group>
    <arm_group_label>doxorubicin + trabectedin followed by maintenance trabectedin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Doxorubicin + trabectedin 6 cycles - 1 cycle every 3 weeks (day 1 to day 21) Doxorubicin 60 mg/m² IV D1, then Trabectedin 1.1 mg/m² per CIV 3 hours D1. Surgery for residual disease is possible after 6 cycles (in case of non evolutive disease)&#xD;
In case of response or stable disease after 6 cycles 3-weeks cycle until disease progression or for a maximum of 12 months of treatment (maximum 17 cycles in maintenance therapy), whichever occurs first Trabectedin 1.1 mg/m² per CIV 3 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>75 mg/m² Day 1 of each 3-weeks cycle</description>
    <arm_group_label>Doxorubicin</arm_group_label>
    <arm_group_label>doxorubicin + trabectedin followed by maintenance trabectedin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trabectedin</intervention_name>
    <description>150 μg/m²/day s.c From day 3 to day 9</description>
    <arm_group_label>doxorubicin + trabectedin followed by maintenance trabectedin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must have histologically confirmed diagnosis of metastatic or relapsed&#xD;
             unresectable uterine or soft tissue leiomyosarcoma, reviewed in a reference center&#xD;
             (among RREPS network), previously untreated with chemotherapy , and with available&#xD;
             Formalin Fixed Paraffin Embedded (FFPE) blocks&#xD;
&#xD;
          2. At least one measurable lesion according to RECIST V 1.1 criteria. Target could be in&#xD;
             a previously irradiated field but has to be progressive or a biopsy had to be positive&#xD;
             before inclusion.&#xD;
&#xD;
          3. Age ≥ 18 years old&#xD;
&#xD;
          4. ECOG performance status &lt; 2 (Appendix 4)&#xD;
&#xD;
          5. Adequate haematological, liver and cardiac functions:&#xD;
&#xD;
               -  Neutrophil counts ≥ 1500/mm3&#xD;
&#xD;
               -  Platelets ≥ 100 000/mm3&#xD;
&#xD;
               -  Serum creatinin &lt; 1.5 x Upper Limit of Normal Value (UNL)&#xD;
&#xD;
               -  Serum bilirubin ≤1 x ULN&#xD;
&#xD;
               -  ALT, AST ≤ 2.5 x ULN&#xD;
&#xD;
               -  Alcaline phosphatases ≤ 1.5 x ULN&#xD;
&#xD;
               -  Cardiac ultrasound and/or normal isotopic ventriculography : Shortening Fraction&#xD;
                  (SF) &gt; 30%, Left Ventricular Ejection Fraction (LVEF) &gt; 50%&#xD;
&#xD;
          6. Creatinin phosphokinase (CPK) ≤ 2.5 x ULN&#xD;
&#xD;
          7. Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7&#xD;
             days prior to inclusion. Both males and WOCBP who are sexually active should be using&#xD;
             an effective birth control method from inclusion (for WOCBP) or treatment initiation&#xD;
             (for male) and up to 6 months following the last dose of study drug.&#xD;
&#xD;
          8. Signed written informed consent form&#xD;
&#xD;
          9. Patient affiliated to a social security regimen or beneficiary of the same&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. All other histological types of uterine sarcomas or soft tissue sarcomas&#xD;
&#xD;
          2. Any contraindication for the use of trabectedin and/or doxorubicin (cardiac, renal,&#xD;
             hepatic, known hypersensitivity…)&#xD;
&#xD;
          3. Patient already enrolled in another therapeutic trial involving an investigational&#xD;
             substance, and when such a substance has been taken during the previous 4 weeks.&#xD;
&#xD;
          4. Medical history of progressive psychiatric disorder&#xD;
&#xD;
          5. History of another type of cancer not in complete remission for more than 3 years&#xD;
             prior to study entry (except for cutaneous basal cell carcinoma or in situ cervical&#xD;
             epithelioma), and/or having required any chemotherapy treatment at any time.&#xD;
&#xD;
          6. Known cerebral metastasis&#xD;
&#xD;
          7. History of allograft or autograft&#xD;
&#xD;
          8. Active viral hepatitis B or C or known human immunodeficiency virus (HIV) infection or&#xD;
             any other uncontrolled infection&#xD;
&#xD;
          9. Pregnant women or nursing mothers&#xD;
&#xD;
         10. Patient under guardianship or deprived of his liberty by a judicial or administrative&#xD;
             decision or any condition (e.g., psychological instability, geographical location,&#xD;
             social reason, etc.) that, in the judgment of the Investigator, may affect the&#xD;
             patient's ability to understand and sign the informed consent or to fully comply with&#xD;
             all study visits, treatments, procedures, and other requirements scheduled in the&#xD;
             protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <state>Val De Marne</state>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <last_update_submitted>December 10, 2021</last_update_submitted>
  <last_update_submitted_qc>December 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leiomyosarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Trabectedin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02997358
org study id: 2016-002186-56
secondary id: 2016/2410
nct id: NCT02997358
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objective of LMS04 study is to better define the treatment strategy for patients with
      metastatic leiomyosarcoma (uterine or soft tissue), as well as identifying the best first
      line therapeutic option for these patients. LMS04 will test a new strategy for first line
      therapy LMS sarcoma compare to the reference therapy (6 cycles of doxorubicin alone): the
      interest of the association of trabectedin to doxorubicin in first line treatment followed by
      trabectedin alone for non-progressive patients after 6 cycles of the association of
      trabectedin and doxorubicin (the LMS02 design).

      LMS04 will be the first phase III randomized study specifically dedicated to soft tissue
      leiomyosarcoma in first line metastatic disease.

      It is planned to compare a new doxorubicin combination (including trabectedin) with very
      encouraging results followed by trabectedin maintenance therapy for non-progressive patients
      to doxorubicin alone. Prospective ancillary translational studies will attempt to define
      profiles of patients who could benefit from this new chemotherapy in an exploratory way.

      The validation of a new first line option specific for LMS, identifying clinical factors that
      characterize aggressiveness and responsiveness to treatment aims to have an important in the
      spirit of personalized medicine in this rare and deadly disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free Survival
time frame: Until progression or 2 years after randomization, whichever occurs first
description: Tumour assessment will be analysed using RECIST 1.1 criteria.
arm group label: Doxorubicin
arm group type: Active Comparator
description: 6 cycles - 1 cycle every 3 weeks (day 1 to day 21) On day 1: Doxorubicin 75 mg/m² IV
arm group label: doxorubicin + trabectedin followed by maintenance trabectedin
arm group type: Experimental
description: Doxorubicin + trabectedin 6 cycles - 1 cycle every 3 weeks (day 1 to day 21) Doxorubicin 60 mg/m² IV D1, then Trabectedin 1.1 mg/m² per CIV 3 hours D1. Surgery for residual disease is possible after 6 cycles (in case of non evolutive disease)
In case of response or stable disease after 6 cycles 3-weeks cycle until disease progression or for a maximum of 12 months of treatment (maximum 17 cycles in maintenance therapy), whichever occurs first Trabectedin 1.1 mg/m² per CIV 3 hours
intervention type: Drug
intervention name: Doxorubicin
description: 75 mg/m² Day 1 of each 3-weeks cycle
arm group label: Doxorubicin
arm group label: doxorubicin + trabectedin followed by maintenance trabectedin
intervention type: Drug
intervention name: Trabectedin
description: 150 μg/m²/day s.c From day 3 to day 9
arm group label: doxorubicin + trabectedin followed by maintenance trabectedin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: France
responsible party type: Sponsor
mesh term: Leiomyosarcoma
mesh term: Doxorubicin
mesh term: Trabectedin
sharing ipd: No