<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/NCT03784014</url>
  </required_header>
  <id_info>
    <org_study_id>C16-40</org_study_id>
    <secondary_id>2017-002851-27</secondary_id>
    <nct_id>NCT03784014</nct_id>
  </id_info>
  <brief_title>Molecular Profiling of Advanced Soft-tissue Sarcomas</brief_title>
  <acronym>MULTISARC</acronym>
  <official_title>Molecular Profiling of Advanced Soft-tissue Sarcomas. A Phase III Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Commissariat A L'energie Atomique</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut Bergonié</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Plateforme labellisée Inca - Institut Bergonié, Bordeaux</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Plateforme labellisée Inca - Hôpital Européen Georges Pompidou, Paris</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>EUCLID Clinical Trial Platform</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institut National de la Santé Et de la Recherche Médicale, France</source>
  <oversight_info>
    <has_dmc>Yes</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>
      MULTISARC is a randomized multicenter study assessing whether high throughput molecular&#xD;
      analysis (next generation sequencing exome - NGS) is feasible in advanced/metastatic&#xD;
      soft-tissue sarcoma patients, that is, whether NGS can be conducted for a large proportion of&#xD;
      patients, with results available within reasonnable delays.&#xD;
&#xD;
      In parallel, MULTISARC aims to assess efficacy of an innovative treatment strategy guided by&#xD;
      high throughput molecular analysis (next generation sequencing exome, RNASeq [NGS]) in&#xD;
      patients with Advanced/metastatic soft-tissue sarcomas. At the end of first-line treatment,&#xD;
      participant's tumor profile of experimental Arm NGS (treatment strategy based on NGS results)&#xD;
      will be discussed within a multidisciplinary tumor board which aims at discussing the genomic&#xD;
      profiles and at providing a therapeutic decision for each participant. Participants for whom&#xD;
      a targetable genomic alteration has been identified will be proposed to enter in one of the&#xD;
      subsequent phase II single-arm sub-trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Screening phase: frozen tumor sample (archived or newly obtained) and blood sample will be&#xD;
      used for genetic profiling. Patients can be considered as pre-eligible for the randomized&#xD;
      phase when all genetic material have been received by the Platform.&#xD;
&#xD;
      Randomization phase: the randomization will allocate the following arms with a ratio 1:1:&#xD;
&#xD;
        -  experimental Arm NGS : treatment strategy based on NGS results [exome, RNASeq]&#xD;
&#xD;
        -  standard Arm No NGS: treatment strategy not based on NGS (Note that for these&#xD;
           participants and under specific conditions, subsequent NGS analyses may be allowed&#xD;
           within the scope of the trial)&#xD;
&#xD;
      Single-arm phase II sub-trial: at the end of the first-line treatment and regardless of tumor&#xD;
      response as per RECIST v1.1, patients randomized in Arm NGS and for whom a targetable&#xD;
      alteration has been identified by the Molecular Tumor Board will be considered as&#xD;
      pre-eligible for the targeted sub-study. The mandatory post-chemotherapy wash-out period of&#xD;
      21 days will provide time to achieve all the required tests and examinations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 19, 2019</start_date>
  <completion_date type="Anticipated">October 2025</completion_date>
  <primary_completion_date type="Anticipated">October 2023</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>
    <intervention_model_description>MULTISARC is a randomized multicenter study assessing whether high throughput molecular analysis (next generation sequencing exome - NGS) is feasible in advanced soft tissue sarcoma participants.&#xD;
In parallel, MULTISARC aims to assess efficacy of an innovative treatment strategy guided by high throughput molecular analysis, in participants with advanced soft-tissue sarcomas.&#xD;
Randomization 1:1 with 1 participant randomized in experimental Arm NGS (treatment strategy based on NGS) and 1 participant randomized in standard Arm No NGS (treatment strategy not based on NGS).&#xD;
At the end of first-line treatment, participant's tumor profile of experimental Arm NGS will be discussed within a multidisciplinary tumor board which aims at discussing the genomic profiles and at providing a therapeutic decision for each participant. Participants for whom a targetable genomic alteration has been identified will be proposed to enter in one of the subsequent phase II single-arm sub-trial.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To assess the feasibility of high throughput molecular analysis (next generation sequencing exome [NGS]</measure>
    <time_frame>7 weeks</time_frame>
    <description>Feasibility will be defined as the proportion of participants for whom results from NGS are (i) interpretable and (ii) for whom a validated report of exome sequencing including a clinical recommendation from the molecular tumor board is available within 7 weeks (i.e. within at most 49 calendar days) after reception of blood and tumor samples by one of the molecular platform.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 1-year progression-free survival (PFS)</measure>
    <time_frame>1 year</time_frame>
    <description>PFS will be defined as the delay from the date of randomization to the date of progression as per RECIST v1.1 (or death, whichever occurs first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 2-year progression-free survival (PFS)</measure>
    <time_frame>2 years</time_frame>
    <description>PFS will be defined as the delay from the date of randomization to the date of progression as per RECIST v1.1 (or death, whichever occurs first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 1-year overall survival (OS)</measure>
    <time_frame>1 year</time_frame>
    <description>OS will be defined as the delay from the date of randomization to the date of death (whatever the cause)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 2-year overall survival (OS)</measure>
    <time_frame>2 years</time_frame>
    <description>OS will be defined as the delay from the date of randomization to the date of death (whatever the cause)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the feasibility of high throughput molecular analysis in terms of delay to obtain a clinical recommendation from the molecular tumor board for patients randomized in arm NGS with interpretable NGS</measure>
    <time_frame>an average of 7 weeks</time_frame>
    <description>Delay from the date of signature of the informed consent to the date of the molecular tumor board</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the proportion of patients with Advanced STS presenting at least one targetable genomic alteration</measure>
    <time_frame>An average of 7 weeks</time_frame>
    <description>A participant will be considered as &quot;presenting at least one targetable genomic alteration&quot;, if the MTB considers that at least one genetic alteration identified can be matched with one of the drugs available through the MULTISARC study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of first-line systemic treatment in terms of 1-year progression-free survival</measure>
    <time_frame>1 year</time_frame>
    <description>PFS will be defined as the delay from the date of onset of first-line treatment to the date of progression as per RECIST v1.1 (or death, whichever occurs first)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of first-line systemic treatment in terms of 2-year progression-free survival</measure>
    <time_frame>2 years</time_frame>
    <description>PFS will be defined as the delay from the date of onset of first-line treatment to the date of progression as per RECIST v1.1 (or death, whichever occurs first)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of first-line systemic treatment in terms of 1-year overall survival</measure>
    <time_frame>1 year</time_frame>
    <description>OS will be defined as the delay from the date of onset of first-line treatment to the date of death (whatever the cause).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of first-line systemic treatment in terms of 2-year overall survival</measure>
    <time_frame>2 years</time_frame>
    <description>OS will be defined as the delay from the date of onset of first-line treatment to the date of death (whatever the cause).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of first-line systemic treatment in terms of best overall response under first-line treatment</measure>
    <time_frame>Throughout the treatment period, an average of 18 weeks</time_frame>
    <description>Best response is recorded from the date of onset of first-line treatment until the end of first-line treatment taking into account any requirement for confirmation as per RECIST v1.1 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of first-line systemic treatment in terms of 6-month objective response</measure>
    <time_frame>6 months</time_frame>
    <description>Objective response is defined as complete or partial response (CR, PR) as per RECIST v1.1 under first-line treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of first-line systemic treatment in terms of 6-month non progression</measure>
    <time_frame>6 months</time_frame>
    <description>Non progression is defined as complete or partial response (CR, PR) or stable disease (SD) under first-line treatment as defined as per RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of each targeted treatment in terms of 6-month non progression</measure>
    <time_frame>6 months</time_frame>
    <description>Non progression is defined as complete or partial response (CR, PR) or stable disease (SD) under targeted treatment as defined as per RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of each targeted treatment in terms of 1-year progression-free survival</measure>
    <time_frame>1 year</time_frame>
    <description>PFS will be defined as the delay from the date of targeted treatment initiation to the date of progression as per RECIST v1.1 or death, whichever occurs first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of each targeted treatment in terms of 1-year overall survival</measure>
    <time_frame>1 year</time_frame>
    <description>OS is defined as the delay from the date of targeted treatment initiation to the date of death (whatever the cause)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of each targeted treatment in terms of best overall response under treatment</measure>
    <time_frame>Throughout the treatment period, an average of 6 months</time_frame>
    <description>Best response (partial or complete, as per RECIST v1.1) recorded from date of targeted treatment initiation taking into account any requirement for confirmation as per RECIST v1.1 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of each targeted treatment in terms of objective response under treatment</measure>
    <time_frame>Throughout the treatment period, an average of 6 months</time_frame>
    <description>Complete response or partial response under targeted treatment as defined as per RECIST evaluation criteria v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the efficacy of each targeted treatment in terms of change in tumor size (CTS)</measure>
    <time_frame>Throughout the treatment period, an average of 6 months</time_frame>
    <description>CTS is defined as the difference (in percentage) in tumor size burden from the date of targeted treatment initiation (baseline) to the tumor assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the safety profile of each targeted treatment using the CTCAE v5</measure>
    <time_frame>Throughout the treatment period, an average of 6 months</time_frame>
    <description>Safety will be assessed as per CTCAE v5</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of the results of immunosequencing during first-line treatment</measure>
    <time_frame>At cycle 2 day 1</time_frame>
    <description>Correlation of TCR-sequencing data with objective response (OR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of the results of immunosequencing during first-line treatment</measure>
    <time_frame>At cycle 2 day 1</time_frame>
    <description>Correlation of TCR-sequencing data with progression-free survival (PFS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of the results of immunosequencing during first-line treatment</measure>
    <time_frame>At cycle 2 day 1</time_frame>
    <description>Correlation of TCR-sequencing data with overall survival (OS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of the results of immunosequencing during targeted treatment</measure>
    <time_frame>At cycle 2 day 1 of targeted treatment</time_frame>
    <description>Correlation of TCR-sequencing data with objective response (OR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of the results of immunosequencing during targeted treatment</measure>
    <time_frame>At cycle 2 day 1 of targeted treatment</time_frame>
    <description>Correlation of TCR-sequencing data with progression-free survival (PFS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of the results of immunosequencing during targeted treatment</measure>
    <time_frame>At cycle 2 day 1 of targeted treatment</time_frame>
    <description>Correlation of TCR-sequencing data with overall survival (OS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To estimate the cost-effectiveness of the strategy usdin NGS as compared to the strategy without NGS</measure>
    <time_frame>Trhoughout the study period, an average of 2 years</time_frame>
    <description>The outcome will be the incremental cost-utility ratio or the incremental cost per incremental Quality Adjusted Life Year (QALY)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the feasibility of NGS in participants who have switched treatment arm for NGS arm in terms of proportion of participants with interpretable NGS results</measure>
    <time_frame>an average of 7 weeks</time_frame>
    <description>Proportion of participants with interpretable NGS results</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the feasibility of NGS in participants who have switched treatment arm for NGS arm in terms of delays</measure>
    <time_frame>an average of 7 weeks</time_frame>
    <description>Delay from the date of treatment failure (progression, investigator decision, end of last treatment line) to the date of the molecular tumor board</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the feasibility of NGS in participants who have switched treatment arm for NGS arm in terms of proportion of participants with interpretable NGS results</measure>
    <time_frame>an average of 7 weeks</time_frame>
    <description>Proportion of participants presenting at least one targetable genomic alteration</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">960</enrollment>
  <condition>Soft Tissue Sarcoma</condition>
  <arm_group>
    <arm_group_label>Arm No NGS</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients will be treated by standard first-line systemic treatment and tumor assessment will be performed every 2 cycles during treatment. Thereafter, disease will be managed as per standard care depending on tumor response observed at the end of the first-line treatment.&#xD;
Note that for these participants and under specific conditions, subsequent NGS analyses may be allowed within the scope of the trial</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm NGS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated by standard first-line systemic treatment and tumor assessment will be performed every 2 cycles during treatment. After tumor assessment at the end of first-line systemic treatment and regardless of tumor response as per RECIST v1.1, participants will be discussed within a multidisciplinary tumor board (molecular tumor board-MTB) which aims at discussing the genomic profiles and at providing a therapeutic decision for each participant.&#xD;
Patients for whom a targetable genomic alteration has been highlighted will be proposed to enter in a subsequent single-arm phase II sub-trials. Otherwise, thereafter, disease will be managed as per standard care depending on tumor response observed at the end of the first-line treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm NGS - Targeted therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Targeted therapy from a list of 10 targeted treatment strategies, guided by the genomic analyses: Nilotinib capsule per os 400 mg bd, continuous dosing ; Ceritinib capsule per os 450 mg od, continuous dosing; Capmatinib tablet per os 400 mg bd, continuous dosing; Lapatinib tablet per os 1500 mg od, continuous dosing; Trametinib tablet per os 2 mg od, continuous dosing; association of Trametinib tablet per os 2 mg od and Dabrafenib capsule per os 150 mg bd, continuous dosing; association of Olaparib tablet per os 300 mg bd, continuous dosing and Durvalumab intra-veinous 1500 mg on day 1, Q4W; Palbociclib capsule 125 mg od, 3 weeks on/1 week off; Glasdegib tablet per os 300 mg od, continuous dosing; TAS-120 tablet per os 20 mg od, continuous dosing.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nilotinib</intervention_name>
    <description>Target: KIT, PDGFRA, CSF1R Nilotinib will be administered orally, 400 mg twice daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.</description>
    <arm_group_label>Arm NGS - Targeted therapy</arm_group_label>
    <other_name>TASIGNA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ceritinib</intervention_name>
    <description>Target: ALK, ROS. Ceritinib will be administered orally, 450mg once daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.</description>
    <arm_group_label>Arm NGS - Targeted therapy</arm_group_label>
    <other_name>ZYKADIA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capmatinib</intervention_name>
    <description>Target: MET. Capmatinib will be administered orally, 400mg twice daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.</description>
    <arm_group_label>Arm NGS - Targeted therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lapatinib</intervention_name>
    <description>Target: ERBB2, EGFR. Lapatinib will be administered orally, 1500mg once daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.</description>
    <arm_group_label>Arm NGS - Targeted therapy</arm_group_label>
    <other_name>TYVERB</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trametinib</intervention_name>
    <description>Target: KRAS, NRAS, HRAS, PTPN11, NF1, MAP2K. Trametinib will be administered orally, 2 mg once daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.</description>
    <arm_group_label>Arm NGS - Targeted therapy</arm_group_label>
    <other_name>MEKINIST</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Trametinib and Dabrafenib</intervention_name>
    <description>Target: KRAS, NRAS, HRAS, PTPN11, NF1, MAP2K, BRAF. Trametinib will be administered orally, 2mg once daily on a continuous basis. Dabrafenib will be administered orally, 150mg twice daily, on a continuous basis.&#xD;
A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.</description>
    <arm_group_label>Arm NGS - Targeted therapy</arm_group_label>
    <other_name>MEKINIST and TAFINLAR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Olaparib and Durvalumab</intervention_name>
    <description>Target: PDL1, PARP. Olaparib will be administered orally, 300mg twice daily on a continuous basis. Dabrafenib will be administered intraveinously, 1500mg on day 1 every 4 weeks. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.</description>
    <arm_group_label>Arm NGS - Targeted therapy</arm_group_label>
    <other_name>LYNPARZA</other_name>
    <other_name>MEDI4736</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palbociclib</intervention_name>
    <description>Target: CDK4, CDK6. Palbociclib will be administered orally, 125mg once daily, 3 weeks on/1 week off.&#xD;
A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.</description>
    <arm_group_label>Arm NGS - Targeted therapy</arm_group_label>
    <other_name>IBRANCE</other_name>
    <other_name>PD-0332991</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glasdegib</intervention_name>
    <description>Target: SMO. Glasdegib will be administered orally, 300 mg once daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.</description>
    <arm_group_label>Arm NGS - Targeted therapy</arm_group_label>
    <other_name>PF-04449913</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAS-120</intervention_name>
    <description>Target: FGFR. TAS-120 will be administered orally, 20 mg once daily on a continuous basis. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation.</description>
    <arm_group_label>Arm NGS - Targeted therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Next Generation sequencing exome</intervention_name>
    <description>Both frozentumor material (archived or newly obtained) and blood sample collection will be used for genetic profiling</description>
    <arm_group_label>Arm NGS</arm_group_label>
    <other_name>RNA Seq</other_name>
    <other_name>NGS</other_name>
    <other_name>High throughput sequencing</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Randomized phase&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years,&#xD;
&#xD;
          -  Histology: soft-tissue sarcoma confirmed by the RRePS Network, as recommended by the&#xD;
             French NCI&#xD;
&#xD;
          -  Unresectable locally advanced and/or metastatic STS&#xD;
&#xD;
          -  No previous systemic treatment for advanced disease,&#xD;
&#xD;
          -  ECOG ≤ 1&#xD;
&#xD;
          -  Adequate hematological and metabolic functions: Hemoglobin &gt; 9 g/dL and albumin &gt; 30&#xD;
             g/L&#xD;
&#xD;
          -  Measurable disease according to RECIST 1.1.&#xD;
&#xD;
          -  Availability of suitable frozen archive tumor material obtained from a metastatic&#xD;
             lesion or advanced disease (not previously treated), or at least one lesion that can&#xD;
             be biopsied for research purpose,&#xD;
&#xD;
          -  Archived FFPE block of specimen tumor sampling obtained anytime during disease&#xD;
             development for research purpose,&#xD;
&#xD;
          -  Eligible to first-line systemic treatment,&#xD;
&#xD;
          -  No prior or concurrent malignant disease diagnosed or treated in the last two years&#xD;
             before inclusion. Note that patients with in situ carcinoma of the cervix, or&#xD;
             adequately treated basal cell or squamous cell carcinoma of the skin, or adequately&#xD;
             treated localized prostate cancer, or other localized cancer under maintenance therapy&#xD;
             can be included as long as they don't limit assessment of efficacy of first-line&#xD;
             systemic therapy&#xD;
&#xD;
          -  Participant with a social security in compliance with the French law,&#xD;
&#xD;
          -  Voluntary signed and dated written informed consent prior to any study specific&#xD;
             procedure (ICF1)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Radiological evidence of symptomatic or progressive brain metastases,&#xD;
&#xD;
          -  Inability to swallow,&#xD;
&#xD;
          -  Major problem with intestinal absorption,&#xD;
&#xD;
          -  Previous allogeneic bone marrow transplant,&#xD;
&#xD;
          -  Evidence of severe or uncontrolled systemic disease (uncontrolled hypertension, active&#xD;
             bleeding diatheses, or active Hepatitis B, C and HIV or active autoimmune disease),&#xD;
&#xD;
          -  Any condition which in the Investigator's opinion makes it undesirable for the subject&#xD;
             to participate in the trial or which would jeopardize compliance with the protocol,&#xD;
&#xD;
          -  Individuals deprived of liberty or placed under guardianship&#xD;
&#xD;
          -  Pregnant or breast feeding women,&#xD;
&#xD;
          -  Men or women refusing contraception,&#xD;
&#xD;
          -  Previous enrolment in the present study,&#xD;
&#xD;
          -  Any contraindication to first-line chemotherapy treatment.&#xD;
&#xD;
        Phase II Sub-trials&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants already enrolled in MULTISARC and randomized/switched in Arm &quot;NGS&quot;,&#xD;
&#xD;
          -  ECOG performance status &lt; 1,&#xD;
&#xD;
          -  Measurable disease according to RECIST v1.1,&#xD;
&#xD;
          -  Molecular alteration identified by molecular profiling,&#xD;
&#xD;
          -  Participants who have received a first-line systemic treatment at the inclusion,&#xD;
&#xD;
          -  Participants must have advanced disease and must not be a candidate for other approved&#xD;
             therapeutic regimen known to provide significant clinical benefit based on&#xD;
             investigator judgement,&#xD;
&#xD;
          -  Participants will have had a minimum of 21 days gap from last chemotherapy or&#xD;
             immunotherapy or any other pharmacological therapy and/or radiotherapy prior to the&#xD;
             first dose of study treatment,&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum pregnancy test within 3&#xD;
             days of enrolment and serum/urine pregnancy test within 24 hours prior to the&#xD;
             administration of the study drug,&#xD;
&#xD;
          -  Female with child bearing potential and male participants with partners of child&#xD;
             bearing potential must be willing to use two effectives forms of contraception (1&#xD;
             highly effective method and 1 barrier method), from beginning 3 weeks before the first&#xD;
             dose of investigational product and until 3 months after discontinuing the study.&#xD;
&#xD;
          -  Participant with a social security in compliance with the French law,&#xD;
&#xD;
          -  Voluntary signed and dated written informed consent (ICF2) prior to any study specific&#xD;
             procedure.&#xD;
&#xD;
        Main exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment with the targeted therapy,&#xD;
&#xD;
          -  No &quot;targetable&quot; genomic alteration generated during the screening phase either due to&#xD;
             the lack of alteration or due to ineligible samples for genomic analysis (MULTISARC),&#xD;
&#xD;
          -  Participants with total gastrectomy,&#xD;
&#xD;
          -  Major surgery within 30 days prior to entry into the study (excluding placement of&#xD;
             vascular access) or minor surgery within 14 days of entry into the study,&#xD;
&#xD;
          -  History of hypersensitivity to involved study drug(s) or of its excipients,&#xD;
&#xD;
          -  Radiological evidence of symptomatic or progressive brain metastases,&#xD;
&#xD;
          -  Participant with oral anticoagulation therapy,&#xD;
&#xD;
          -  Inability to swallow,&#xD;
&#xD;
          -  Major problem with intestinal absorption,&#xD;
&#xD;
          -  Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the&#xD;
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion&#xD;
             criteria. Participants with Grade ≥2 neuropathy will be evaluated on a case-by-case&#xD;
             basis after consultation with the Sponsor.&#xD;
&#xD;
          -  Previous allogeneic bone marrow transplant,&#xD;
&#xD;
          -  Altered hematopoietic or organ function,&#xD;
&#xD;
          -  Mean resting corrected QT interval (QTcF)&gt;470msec obtained from 3 consecutive ECGs&#xD;
&#xD;
          -  Previous or current maligancies of other histologies within the last 2 years, with the&#xD;
             exception of in situ carcinoma of the cervix, and adequately treated basal cell or&#xD;
             squamous cell carcinoma of the skin and prostate cancer,&#xD;
&#xD;
          -  Evidence of severe or uncontrolled systemic disease (uncontrolled hypertension, active&#xD;
             bleeding diatheses), active uncontrolled systemic bacterial, viral, or fungal&#xD;
             infection &gt; Grade 2 as per NCI CTCAE v5.0&#xD;
&#xD;
          -  Chronic or active hepatitis B or hepatitis C. Testing for hepatitis B surface antigen&#xD;
             (HBs Ag) and hepatitis B core antibody (anti HBc) will be performed at screening,&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV) positive,&#xD;
&#xD;
          -  Any condition which in the Investigator's opinion makes it undesirable for the subject&#xD;
             to participate in the trial or which would jeopardize compliance with the protocol,&#xD;
&#xD;
          -  Individuals deprived of liberty or placed under guardianship,&#xD;
&#xD;
          -  Pregnant or breast feeding women.&#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>Antoine Italiano</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut Bergonié</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Helene Esperou</last_name>
    <phone>+33 1 44 23 67 00</phone>
    <email>C16-40@inserm.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Institut Bergonie</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antoine ITALIANO</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Jean Perrin</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pascale DUBRAY-LONGERAS</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Georges François Leclerc</name>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Isabelle DESMOULINS</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Oscar Lambret</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Nicolas PENEL</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Léon Bérard</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Yves BLAY</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hôpital La Timone</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Florence DUFFAUD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Paoli Calmettes</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>François BERTUCCI</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de Montpellier</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Didier CUPISSOL</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Antoine Lacassagne</name>
      <address>
        <city>Nice</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>ESMA SAADA-BOUZID, MD</last_name>
      <email>esma.saada-bouzid@nice.unicancer.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hôpital Cochin</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pascaline BOUDOU-ROUQUETTE</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hôpital Pitié Salpétrière</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aurore VOZY</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Curie</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sarah Watson</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CHU Poitiers</name>
      <address>
        <city>Poitiers</city>
        <zip>86000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Nicolas ISAMBERT</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Henri Becquerel</name>
      <address>
        <city>Rouen</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jean-Christophe THERY</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de l'Ouest - Site René Gauducheau</name>
      <address>
        <city>Saint-Herblain</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emmanuelle BOMPAS</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>ICANS - Institut de Cancérologie Strasbourg</name>
      <address>
        <city>Strasbourg</city>
        <zip>67033</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Justine Gantzer</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>IUCT Oncopôle</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Christine CHEVREAU</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olivier MIR</last_name>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>December 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>October 4, 2022</last_update_submitted>
  <last_update_submitted_qc>October 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>advanced disease</keyword>
  <keyword>metastatic disease</keyword>
  <keyword>Next generation sequencing exome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Olaparib</mesh_term>
    <mesh_term>Palbociclib</mesh_term>
    <mesh_term>Lapatinib</mesh_term>
    <mesh_term>Trametinib</mesh_term>
    <mesh_term>Dabrafenib</mesh_term>
    <mesh_term>Ceritinib</mesh_term>
    <mesh_term>Futibatinib</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/NCT03784014
org study id: C16-40
secondary id: 2017-002851-27
nct id: NCT03784014
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
MULTISARC is a randomized multicenter study assessing whether high throughput molecular
      analysis (next generation sequencing exome - NGS) is feasible in advanced/metastatic
      soft-tissue sarcoma patients, that is, whether NGS can be conducted for a large proportion of
      patients, with results available within reasonnable delays.

      In parallel, MULTISARC aims to assess efficacy of an innovative treatment strategy guided by
      high throughput molecular analysis (next generation sequencing exome, RNASeq [NGS]) in
      patients with Advanced/metastatic soft-tissue sarcomas. At the end of first-line treatment,
      participant's tumor profile of experimental Arm NGS (treatment strategy based on NGS results)
      will be discussed within a multidisciplinary tumor board which aims at discussing the genomic
      profiles and at providing a therapeutic decision for each participant. Participants for whom
      a targetable genomic alteration has been identified will be proposed to enter in one of the
      subsequent phase II single-arm sub-trial.
Screening phase: frozen tumor sample (archived or newly obtained) and blood sample will be
      used for genetic profiling. Patients can be considered as pre-eligible for the randomized
      phase when all genetic material have been received by the Platform.

      Randomization phase: the randomization will allocate the following arms with a ratio 1:1:

        -  experimental Arm NGS : treatment strategy based on NGS results [exome, RNASeq]

        -  standard Arm No NGS: treatment strategy not based on NGS (Note that for these
           participants and under specific conditions, subsequent NGS analyses may be allowed
           within the scope of the trial)

      Single-arm phase II sub-trial: at the end of the first-line treatment and regardless of tumor
      response as per RECIST v1.1, patients randomized in Arm NGS and for whom a targetable
      alteration has been identified by the Molecular Tumor Board will be considered as
      pre-eligible for the targeted sub-study. The mandatory post-chemotherapy wash-out period of
      21 days will provide time to achieve all the required tests and examinations.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: MULTISARC is a randomized multicenter study assessing whether high throughput molecular analysis (next generation sequencing exome - NGS) is feasible in advanced soft tissue sarcoma participants.
In parallel, MULTISARC aims to assess efficacy of an innovative treatment strategy guided by high throughput molecular analysis, in participants with advanced soft-tissue sarcomas.
Randomization 1:1 with 1 participant randomized in experimental Arm NGS (treatment strategy based on NGS) and 1 participant randomized in standard Arm No NGS (treatment strategy not based on NGS).
At the end of first-line treatment, participant's tumor profile of experimental Arm NGS will be discussed within a multidisciplinary tumor board which aims at discussing the genomic profiles and at providing a therapeutic decision for each participant. Participants for whom a targetable genomic alteration has been identified will be proposed to enter in one of the subsequent phase II single-arm sub-trial.
primary purpose: Health Services Research
masking: None (Open Label)
measure: To assess the feasibility of high throughput molecular analysis (next generation sequencing exome [NGS]
time frame: 7 weeks
description: Feasibility will be defined as the proportion of participants for whom results from NGS are (i) interpretable and (ii) for whom a validated report of exome sequencing including a clinical recommendation from the molecular tumor board is available within 7 weeks (i.e. within at most 49 calendar days) after reception of blood and tumor samples by one of the molecular platform.
measure: Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 1-year progression-free survival (PFS)
time frame: 1 year
description: PFS will be defined as the delay from the date of randomization to the date of progression as per RECIST v1.1 (or death, whichever occurs first
measure: Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 2-year progression-free survival (PFS)
time frame: 2 years
description: PFS will be defined as the delay from the date of randomization to the date of progression as per RECIST v1.1 (or death, whichever occurs first
measure: Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 1-year overall survival (OS)
time frame: 1 year
description: OS will be defined as the delay from the date of randomization to the date of death (whatever the cause)
measure: Comparison of the efficacy of the 2 treatment strategies (NGS vs No NGS) in terms of 2-year overall survival (OS)
time frame: 2 years
description: OS will be defined as the delay from the date of randomization to the date of death (whatever the cause)
measure: Assessment of the feasibility of high throughput molecular analysis in terms of delay to obtain a clinical recommendation from the molecular tumor board for patients randomized in arm NGS with interpretable NGS
time frame: an average of 7 weeks
description: Delay from the date of signature of the informed consent to the date of the molecular tumor board
measure: Assessment of the proportion of patients with Advanced STS presenting at least one targetable genomic alteration
time frame: An average of 7 weeks
description: A participant will be considered as "presenting at least one targetable genomic alteration", if the MTB considers that at least one genetic alteration identified can be matched with one of the drugs available through the MULTISARC study
measure: Assessment of the efficacy of first-line systemic treatment in terms of 1-year progression-free survival
time frame: 1 year
description: PFS will be defined as the delay from the date of onset of first-line treatment to the date of progression as per RECIST v1.1 (or death, whichever occurs first)
measure: Assessment of the efficacy of first-line systemic treatment in terms of 2-year progression-free survival
time frame: 2 years
description: PFS will be defined as the delay from the date of onset of first-line treatment to the date of progression as per RECIST v1.1 (or death, whichever occurs first)
measure: Assessment of the efficacy of first-line systemic treatment in terms of 1-year overall survival
time frame: 1 year
description: OS will be defined as the delay from the date of onset of first-line treatment to the date of death (whatever the cause).
measure: Assessment of the efficacy of first-line systemic treatment in terms of 2-year overall survival
time frame: 2 years
description: OS will be defined as the delay from the date of onset of first-line treatment to the date of death (whatever the cause).
measure: Assessment of the efficacy of first-line systemic treatment in terms of best overall response under first-line treatment
time frame: Throughout the treatment period, an average of 18 weeks
description: Best response is recorded from the date of onset of first-line treatment until the end of first-line treatment taking into account any requirement for confirmation as per RECIST v1.1 criteria
measure: Assessment of the efficacy of first-line systemic treatment in terms of 6-month objective response
time frame: 6 months
description: Objective response is defined as complete or partial response (CR, PR) as per RECIST v1.1 under first-line treatment
measure: Assessment of the efficacy of first-line systemic treatment in terms of 6-month non progression
time frame: 6 months
description: Non progression is defined as complete or partial response (CR, PR) or stable disease (SD) under first-line treatment as defined as per RECIST v1.1
measure: Assessment of the efficacy of each targeted treatment in terms of 6-month non progression
time frame: 6 months
description: Non progression is defined as complete or partial response (CR, PR) or stable disease (SD) under targeted treatment as defined as per RECIST v1.1
measure: Assessment of the efficacy of each targeted treatment in terms of 1-year progression-free survival
time frame: 1 year
description: PFS will be defined as the delay from the date of targeted treatment initiation to the date of progression as per RECIST v1.1 or death, whichever occurs first
measure: Assessment of the efficacy of each targeted treatment in terms of 1-year overall survival
time frame: 1 year
description: OS is defined as the delay from the date of targeted treatment initiation to the date of death (whatever the cause)
measure: Assessment of the efficacy of each targeted treatment in terms of best overall response under treatment
time frame: Throughout the treatment period, an average of 6 months
description: Best response (partial or complete, as per RECIST v1.1) recorded from date of targeted treatment initiation taking into account any requirement for confirmation as per RECIST v1.1 criteria
measure: Assessment of the efficacy of each targeted treatment in terms of objective response under treatment
time frame: Throughout the treatment period, an average of 6 months
description: Complete response or partial response under targeted treatment as defined as per RECIST evaluation criteria v1.1
measure: Assessment of the efficacy of each targeted treatment in terms of change in tumor size (CTS)
time frame: Throughout the treatment period, an average of 6 months
description: CTS is defined as the difference (in percentage) in tumor size burden from the date of targeted treatment initiation (baseline) to the tumor assessment
measure: Assessment of the safety profile of each targeted treatment using the CTCAE v5
time frame: Throughout the treatment period, an average of 6 months
description: Safety will be assessed as per CTCAE v5
measure: Impact of the results of immunosequencing during first-line treatment
time frame: At cycle 2 day 1
description: Correlation of TCR-sequencing data with objective response (OR)
measure: Impact of the results of immunosequencing during first-line treatment
time frame: At cycle 2 day 1
description: Correlation of TCR-sequencing data with progression-free survival (PFS)
measure: Impact of the results of immunosequencing during first-line treatment
time frame: At cycle 2 day 1
description: Correlation of TCR-sequencing data with overall survival (OS)
measure: Impact of the results of immunosequencing during targeted treatment
time frame: At cycle 2 day 1 of targeted treatment
description: Correlation of TCR-sequencing data with objective response (OR)
measure: Impact of the results of immunosequencing during targeted treatment
time frame: At cycle 2 day 1 of targeted treatment
description: Correlation of TCR-sequencing data with progression-free survival (PFS)
measure: Impact of the results of immunosequencing during targeted treatment
time frame: At cycle 2 day 1 of targeted treatment
description: Correlation of TCR-sequencing data with overall survival (OS)
measure: To estimate the cost-effectiveness of the strategy usdin NGS as compared to the strategy without NGS
time frame: Trhoughout the study period, an average of 2 years
description: The outcome will be the incremental cost-utility ratio or the incremental cost per incremental Quality Adjusted Life Year (QALY)
measure: To assess the feasibility of NGS in participants who have switched treatment arm for NGS arm in terms of proportion of participants with interpretable NGS results
time frame: an average of 7 weeks
description: Proportion of participants with interpretable NGS results
measure: To assess the feasibility of NGS in participants who have switched treatment arm for NGS arm in terms of delays
time frame: an average of 7 weeks
description: Delay from the date of treatment failure (progression, investigator decision, end of last treatment line) to the date of the molecular tumor board
measure: To assess the feasibility of NGS in participants who have switched treatment arm for NGS arm in terms of proportion of participants with interpretable NGS results
time frame: an average of 7 weeks
description: Proportion of participants presenting at least one targetable genomic alteration
arm group label: Arm No NGS
arm group type: No Intervention
description: Patients will be treated by standard first-line systemic treatment and tumor assessment will be performed every 2 cycles during treatment. Thereafter, disease will be managed as per standard care depending on tumor response observed at the end of the first-line treatment.
Note that for these participants and under specific conditions, subsequent NGS analyses may be allowed within the scope of the trial
arm group label: Arm NGS
arm group type: Experimental
description: Patients will be treated by standard first-line systemic treatment and tumor assessment will be performed every 2 cycles during treatment. After tumor assessment at the end of first-line systemic treatment and regardless of tumor response as per RECIST v1.1, participants will be discussed within a multidisciplinary tumor board (molecular tumor board-MTB) which aims at discussing the genomic profiles and at providing a therapeutic decision for each participant.
Patients for whom a targetable genomic alteration has been highlighted will be proposed to enter in a subsequent single-arm phase II sub-trials. Otherwise, thereafter, disease will be managed as per standard care depending on tumor response observed at the end of the first-line treatment
arm group label: Arm NGS - Targeted therapy
arm group type: Experimental
description: Targeted therapy from a list of 10 targeted treatment strategies, guided by the genomic analyses: Nilotinib capsule per os 400 mg bd, continuous dosing ; Ceritinib capsule per os 450 mg od, continuous dosing; Capmatinib tablet per os 400 mg bd, continuous dosing; Lapatinib tablet per os 1500 mg od, continuous dosing; Trametinib tablet per os 2 mg od, continuous dosing; association of Trametinib tablet per os 2 mg od and Dabrafenib capsule per os 150 mg bd, continuous dosing; association of Olaparib tablet per os 300 mg bd, continuous dosing and Durvalumab intra-veinous 1500 mg on day 1, Q4W; Palbociclib capsule 125 mg od, 3 weeks on/1 week off; Glasdegib tablet per os 300 mg od, continuous dosing; TAS-120 tablet per os 20 mg od, continuous dosing.
intervention type: Drug
intervention name: Nilotinib
description: Target: KIT, PDGFRA, CSF1R Nilotinib will be administered orally, 400 mg twice daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.
arm group label: Arm NGS - Targeted therapy
other name: TASIGNA
intervention type: Drug
intervention name: Ceritinib
description: Target: ALK, ROS. Ceritinib will be administered orally, 450mg once daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.
arm group label: Arm NGS - Targeted therapy
other name: ZYKADIA
intervention type: Drug
intervention name: Capmatinib
description: Target: MET. Capmatinib will be administered orally, 400mg twice daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.
arm group label: Arm NGS - Targeted therapy
intervention type: Drug
intervention name: Lapatinib
description: Target: ERBB2, EGFR. Lapatinib will be administered orally, 1500mg once daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.
arm group label: Arm NGS - Targeted therapy
other name: TYVERB
intervention type: Drug
intervention name: Trametinib
description: Target: KRAS, NRAS, HRAS, PTPN11, NF1, MAP2K. Trametinib will be administered orally, 2 mg once daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.
arm group label: Arm NGS - Targeted therapy
other name: MEKINIST
intervention type: Combination Product
intervention name: Trametinib and Dabrafenib
description: Target: KRAS, NRAS, HRAS, PTPN11, NF1, MAP2K, BRAF. Trametinib will be administered orally, 2mg once daily on a continuous basis. Dabrafenib will be administered orally, 150mg twice daily, on a continuous basis.
A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.
arm group label: Arm NGS - Targeted therapy
other name: MEKINIST and TAFINLAR
intervention type: Combination Product
intervention name: Olaparib and Durvalumab
description: Target: PDL1, PARP. Olaparib will be administered orally, 300mg twice daily on a continuous basis. Dabrafenib will be administered intraveinously, 1500mg on day 1 every 4 weeks. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.
arm group label: Arm NGS - Targeted therapy
other name: LYNPARZA
other name: MEDI4736
intervention type: Drug
intervention name: Palbociclib
description: Target: CDK4, CDK6. Palbociclib will be administered orally, 125mg once daily, 3 weeks on/1 week off.
A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.
arm group label: Arm NGS - Targeted therapy
other name: IBRANCE
other name: PD-0332991
intervention type: Drug
intervention name: Glasdegib
description: Target: SMO. Glasdegib will be administered orally, 300 mg once daily on a continuous basis. A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation.
arm group label: Arm NGS - Targeted therapy
other name: PF-04449913
intervention type: Drug
intervention name: TAS-120
description: Target: FGFR. TAS-120 will be administered orally, 20 mg once daily on a continuous basis. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation.
arm group label: Arm NGS - Targeted therapy
intervention type: Other
intervention name: Next Generation sequencing exome
description: Both frozentumor material (archived or newly obtained) and blood sample collection will be used for genetic profiling
arm group label: Arm NGS
other name: RNA Seq
other name: NGS
other name: High throughput sequencing
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Antoine Italiano
role: Principal Investigator
affiliation: Institut Bergonié
last name: Helene Esperou
phone: +33 1 44 23 67 00
email: C16-40@inserm.fr
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status: Recruiting
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country: France
responsible party type: Sponsor
mesh term: Sarcoma
mesh term: Durvalumab
mesh term: Olaparib
mesh term: Palbociclib
mesh term: Lapatinib
mesh term: Trametinib
mesh term: Dabrafenib
mesh term: Ceritinib
mesh term: Futibatinib