<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/NCT03805022</url>
  </required_header>
  <id_info>
    <org_study_id>IB 2017-04</org_study_id>
    <secondary_id>2018-000186-36</secondary_id>
    <nct_id>NCT03805022</nct_id>
  </id_info>
  <brief_title>Benefit of Intensified Peri-operative Chemotherapy Within High-risk CINSARC Patients With Resectable Soft-tissue Sarcomas</brief_title>
  <acronym>CIRSARC</acronym>
  <official_title>Phase III Trial Investigating the Potential Benefit of Intensified Peri-operative Chemotherapy With in High-risk CINSARC Patients With Resectable Soft-tissue SARComas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut Bergonié</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chugai Pharma France</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Institut Bergonié</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>
      The primary objective of this trial is to investigate whether the addition of 3 additional&#xD;
      neo-adjuvant cycles of chemotherapy (doxorubicin based chemotherapy) to standard management&#xD;
      according to the ISG-STS 10-01 study (3 cycles of neoadjuvant doxorubicin based chemotherapy&#xD;
      + surgery +/- radiotherapy) improves the outcome of high-risk CINSARC patients with&#xD;
      resectable soft-tissue sarcoma (STS). Primary endpoint is metastatic progression-free&#xD;
      survival (M-PFS, after 3 years of follow-up).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For high-risk CINSARC patients, this is a multicenter randomized two-arm phase III trial,&#xD;
      with a ratio 1:1:&#xD;
&#xD;
        -  Arm A: standard management (3 cycles of neoadjuvant doxorubicin based chemotherapy +&#xD;
           surgery +/- radiotherapy)&#xD;
&#xD;
        -  Arm B: experimental arm (6 cycles of neoadjuvant doxorubicin based chemotherapy +&#xD;
           surgery +/- radiotherapy)&#xD;
&#xD;
      For low-risk CINSARC patients, this a multicenter prospective cohort with treatment at the&#xD;
      discretion of the investigator.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 14, 2019</start_date>
  <completion_date type="Anticipated">February 2025</completion_date>
  <primary_completion_date type="Anticipated">February 2025</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>This is a multicenter trial with:&#xD;
An open randomized two-arm phase III trial for high-risk CINSARC patients assessing whether the addition of 3 additional neo-adjuvant cycles of chemotherapy (doxorubicin based chemotherapy) to standard management (3 cycles of neoadjuvant anthracycline based chemotherapy + surgery +/- radiotherapy) improves the outcome of patients&#xD;
a prospective cohort for low-risk CINSARC patients.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Metastasis progression-free survival in High-risk CINSARC patients</measure>
    <time_frame>3 years</time_frame>
    <description>Metastasis progression-free survival (M-PFS) defined as the time interval between the date of randomization and the date of death or distant progression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Loco-regional relapse-free survival in High-risk CINSARC patients</measure>
    <time_frame>3 years</time_frame>
    <description>Loco-regional relapse-free survival (LR-RFS) defined as the time interval between the randomization date and the date of death or loco-regional progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival in High-risk CINSARC patients</measure>
    <time_frame>3 years</time_frame>
    <description>Progression-free survival (PFS) defined as the time interval between the randomization date and the date of death or progression (as per RECIST v1.1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival in High-risk CINSARC patients</measure>
    <time_frame>3 years</time_frame>
    <description>Overall survival (OS) defined as the time interval between the randomization date and the date of death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best overall response in High-risk CINSARC patients</measure>
    <time_frame>Throughout the treatment period, an average of 6 months</time_frame>
    <description>Best overall response under treatment as per RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histological response in High-risk CINSARC patients</measure>
    <time_frame>An average of 6 months</time_frame>
    <description>Histological response defined as the proportion of recognizable cells on the tumor sample.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety profile in High-risk CINSARC patients</measure>
    <time_frame>Throughout the treatment period, an average of 6 months</time_frame>
    <description>Toxicity graded using the common toxicity criteria from the NCI v5.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival in Low-risk CINSARC patients</measure>
    <time_frame>3 years</time_frame>
    <description>Progression-free survival defined as the time interval between the randomization date and the date of death or progression (as per RECIST v1.1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metastasis progression-free survival in Low-risk CINSARC patients</measure>
    <time_frame>3 years</time_frame>
    <description>Metastasis progression-free survival defined as the time interval between the inclusion date and the date of death or distant progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Loco-regional progression-free survival in Low-risk CINSARC patients</measure>
    <time_frame>3 years</time_frame>
    <description>Description of the treatment efficacy in terms of 3-years loco-regional progression-free survival defined as the time interval between the randomization date and the date of death or loco-regional progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival in Low-risk CINSARC patients</measure>
    <time_frame>3 years</time_frame>
    <description>Overall survival defined as the time interval between the inclusion date and the date of death.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">351</enrollment>
  <condition>Non-metastatic Soft-tissue Sarcoma</condition>
  <condition>Resectable</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Control-Arm phase III high-risk CINSARC:&#xD;
Patients will be treated by doxorubicin (60 or 75mg/m² day or 20- or 25 mg/m² per day from day1 to day 3) + ifosfamide (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices of a 21-days cycle for up to 3 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental-Arm phase III high-risk CINSARC:&#xD;
Patients will be treated by doxorubicin (60 or 75mg/m² day or 20 or 25 mg/m² per day from day1 to day 3) + ifosfamide (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices of a 21-days cycle for up to 6 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prospective cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated at the discretion of the investigator</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>A treatment cycle consists of 3 weeks. Doxorubicin will be administered from day 1 to day 3 (60 or 75mg/m² day or 20 or 25 mg/m² per day), repeated every 3 weeks, up to 3 cycles.</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ifosfamide or dacarbazine</intervention_name>
    <description>A treatment cycle consists of 3 weeks. Treatment may continue up to 3 cycles. Ifosfamide will be administered from day 1 to day 3 (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices, repeated every 3 weeks, up to 3 cycles.</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>A treatment cycle consists of 3 weeks. Doxorubicin will be administered from day 1 to day 3 (60 or 75mg/m² day or 20 or 25 mg/m² per day), repeated every 3 weeks, up to 6 cycles.</description>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ifosfamide or dacarbazine</intervention_name>
    <description>A treatment cycle consists of 3 weeks. Ifosfamide will be administered from day 1 to day 3 (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices, repeated every 3 weeks, up to 6 cycles.</description>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>At the discretion of the investigator</intervention_name>
    <description>Drug at the discretion of the investigator.</description>
    <arm_group_label>Prospective cohort</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria :&#xD;
&#xD;
          1. Histologically confirmed soft-tissue sarcoma by the RRePS (Réseau de Référence en&#xD;
             Pathologie des Sarcomes et des Viscères) network, as recommended by the French NCI,&#xD;
&#xD;
          2. Grade 2 or 3 according to the FNCLCC grading system,&#xD;
&#xD;
          3. Available archived tumour sample for research purpose,&#xD;
&#xD;
          4. Non-metastatic and resectable disease,&#xD;
&#xD;
          5. No prior treatment for the disease under study,&#xD;
&#xD;
          6. Age ≥ 18 years,&#xD;
&#xD;
          7. Life expectancy ≥ 3 months,&#xD;
&#xD;
          8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1,&#xD;
&#xD;
          9. Patients must have measurable disease (lesion in previously irradiated field can be&#xD;
             considered as measurable if progressive at inclusion according to RECIST 1.1) defined&#xD;
             as per RECIST v1.1 with at least one lesion that can be measured in at least one&#xD;
             dimension (longest diameter to be recorded) as ≥ 10 mm or ≥ 15mm in case of&#xD;
             adenopathy,&#xD;
&#xD;
         10. Women of childbearing potential must have a negative serum pregnancy test before study&#xD;
             entry. Both women and men must agree to use a medically acceptable method of&#xD;
             contraception throughout the treatment period and for one year after discontinuation&#xD;
             of treatment. Acceptable methods of contraception include intrauterine device (IUD),&#xD;
             oral contraceptive, subdermal implant and double barrier. Subjects of childbearing&#xD;
             potential are those who have not been surgically sterilized (e.g., vasectomy for males&#xD;
             and hysterectomy for females) or have not been free from menses for ≥ 1 year,&#xD;
&#xD;
         11. Voluntarily signed and dated written informed consents prior to any study specific&#xD;
             procedure,&#xD;
&#xD;
         12. Patients with a social security in compliance with the French law.&#xD;
&#xD;
        Exclusion Criteria :&#xD;
&#xD;
          1. Soft-tissue sarcoma with the following histological subtypes: well-differentiated&#xD;
             liposarcoma, alveolar soft-part sarcoma, dermatofibrosarcoma protuberans, clearcell&#xD;
             sarcoma, embryonal and alveolar rhabdomyosarcoma,&#xD;
&#xD;
          2. Prior or concurrent malignant disease diagnosed or treated in the last 2 years except&#xD;
             for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell&#xD;
             carcinoma, or in situ transitional bladder cell carcinoma,&#xD;
&#xD;
          3. Any other contraindication to anthracycline, ifosfamide or dacarbazine chemotherapy,&#xD;
&#xD;
          4. Participation to a study involving a medical or therapeutic intervention in the last&#xD;
             28 days,&#xD;
&#xD;
          5. Known infection with HIV, hepatitis B, or hepatitis C,&#xD;
&#xD;
          6. Females who are pregnant or breast-feeding,&#xD;
&#xD;
          7. Other medical conditions may interfere with the conduct of the study and, in the&#xD;
             judgment of the investigator, would make the patient inappropriate for entry into this&#xD;
             study,&#xD;
&#xD;
          8. Individuals deprived of liberty or placed under legal guardianship,&#xD;
&#xD;
          9. Unwillingness or inability to comply with the study protocol for any reason.&#xD;
&#xD;
        Additional criteria for randomization :&#xD;
&#xD;
          1. High-risk CINSARC signature,&#xD;
&#xD;
          2. No more than two cycle of neo-adjuvant anthracycline-based chemotherapy before&#xD;
             randomization.&#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_contact>
    <last_name>Antoine ITALIANO, MD, PhD</last_name>
    <phone>+33 5.56.33.33.33</phone>
    <email>a.italiano@bordeaux.unicancer.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Simone MATHOULIN-PELISSIER, MD, PhD</last_name>
    <email>m.mathoulin@bordeaux.unicancer.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Institut Bergonie</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antoine ITALIANO, MD, PhD</last_name>
      <email>a.italiano@bordeaux.unicancer.fr</email>
    </contact>
    <investigator>
      <last_name>Antoine ITALIANO</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Georges François Leclerc</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nicolas ISAMBERT</last_name>
    </contact>
    <investigator>
      <last_name>Nicolas ISAMBERT, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Dupuytren</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Valérie LEBRUN-LY, MD</last_name>
    </contact>
    <investigator>
      <last_name>Valérie LEBRUN-LY, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Léon Bérard</name>
      <address>
        <city>Lyon Cedex 08</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Yves BLAY, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Jean-Yves BLAY, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Paoli Calmettes</name>
      <address>
        <city>Marseille</city>
        <zip>13273</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>François BERTUCCI, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>François BERTUCCI, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Insitut du Cancer</name>
      <address>
        <city>Montpellier</city>
        <zip>34298</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nelly FIRMIN, MD</last_name>
      <email>nelly.firmin@icm.unicancer.fr</email>
    </contact>
    <investigator>
      <last_name>Nelly FIRMIN, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de l'Ouest - Site René Gauducheau</name>
      <address>
        <city>Saint-Herblain</city>
        <zip>44805</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emmanuelle BOMPAS, MD</last_name>
    </contact>
    <investigator>
      <last_name>Emmanuelle BOMPAS, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU Strasbourg</name>
      <address>
        <city>Strasbourg</city>
        <zip>67200</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Emmanuel KURTZ, MD, PhD</last_name>
      <email>je.kurtz@icans.eu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Claudius Regaud</name>
      <address>
        <city>Toulouse</city>
        <zip>31052</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christine CHEVREAU</last_name>
      <email>chevreau.christine@iuct-oncopole.fr</email>
    </contact>
    <investigator>
      <last_name>Christine CHEVREAU</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94800</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Axel LE CESNE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Axel LE CESNE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 10, 2019</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <last_update_submitted>February 28, 2023</last_update_submitted>
  <last_update_submitted_qc>February 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Solid tumor</keyword>
  <keyword>Phase III trial</keyword>
  <keyword>Soft-tissue sarcoma</keyword>
  <keyword>Resectable</keyword>
  <keyword>Non-metastatic</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>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
    <mesh_term>Ifosfamide</mesh_term>
    <mesh_term>Isophosphamide mustard</mesh_term>
    <mesh_term>Dacarbazine</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/NCT03805022
org study id: IB 2017-04
secondary id: 2018-000186-36
nct id: NCT03805022
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The primary objective of this trial is to investigate whether the addition of 3 additional
      neo-adjuvant cycles of chemotherapy (doxorubicin based chemotherapy) to standard management
      according to the ISG-STS 10-01 study (3 cycles of neoadjuvant doxorubicin based chemotherapy
      + surgery +/- radiotherapy) improves the outcome of high-risk CINSARC patients with
      resectable soft-tissue sarcoma (STS). Primary endpoint is metastatic progression-free
      survival (M-PFS, after 3 years of follow-up).
For high-risk CINSARC patients, this is a multicenter randomized two-arm phase III trial,
      with a ratio 1:1:

        -  Arm A: standard management (3 cycles of neoadjuvant doxorubicin based chemotherapy +
           surgery +/- radiotherapy)

        -  Arm B: experimental arm (6 cycles of neoadjuvant doxorubicin based chemotherapy +
           surgery +/- radiotherapy)

      For low-risk CINSARC patients, this a multicenter prospective cohort with treatment at the
      discretion of the investigator.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a multicenter trial with:
An open randomized two-arm phase III trial for high-risk CINSARC patients assessing whether the addition of 3 additional neo-adjuvant cycles of chemotherapy (doxorubicin based chemotherapy) to standard management (3 cycles of neoadjuvant anthracycline based chemotherapy + surgery +/- radiotherapy) improves the outcome of patients
a prospective cohort for low-risk CINSARC patients.
primary purpose: Treatment
masking: None (Open Label)
measure: Metastasis progression-free survival in High-risk CINSARC patients
time frame: 3 years
description: Metastasis progression-free survival (M-PFS) defined as the time interval between the date of randomization and the date of death or distant progression.
measure: Loco-regional relapse-free survival in High-risk CINSARC patients
time frame: 3 years
description: Loco-regional relapse-free survival (LR-RFS) defined as the time interval between the randomization date and the date of death or loco-regional progression.
measure: Progression-free survival in High-risk CINSARC patients
time frame: 3 years
description: Progression-free survival (PFS) defined as the time interval between the randomization date and the date of death or progression (as per RECIST v1.1).
measure: Overall survival in High-risk CINSARC patients
time frame: 3 years
description: Overall survival (OS) defined as the time interval between the randomization date and the date of death.
measure: Best overall response in High-risk CINSARC patients
time frame: Throughout the treatment period, an average of 6 months
description: Best overall response under treatment as per RECIST v1.1.
measure: Histological response in High-risk CINSARC patients
time frame: An average of 6 months
description: Histological response defined as the proportion of recognizable cells on the tumor sample.
measure: Safety profile in High-risk CINSARC patients
time frame: Throughout the treatment period, an average of 6 months
description: Toxicity graded using the common toxicity criteria from the NCI v5.
measure: Progression-free survival in Low-risk CINSARC patients
time frame: 3 years
description: Progression-free survival defined as the time interval between the randomization date and the date of death or progression (as per RECIST v1.1).
measure: Metastasis progression-free survival in Low-risk CINSARC patients
time frame: 3 years
description: Metastasis progression-free survival defined as the time interval between the inclusion date and the date of death or distant progression.
measure: Loco-regional progression-free survival in Low-risk CINSARC patients
time frame: 3 years
description: Description of the treatment efficacy in terms of 3-years loco-regional progression-free survival defined as the time interval between the randomization date and the date of death or loco-regional progression.
measure: Overall survival in Low-risk CINSARC patients
time frame: 3 years
description: Overall survival defined as the time interval between the inclusion date and the date of death.
arm group label: Arm A
arm group type: Experimental
description: Control-Arm phase III high-risk CINSARC:
Patients will be treated by doxorubicin (60 or 75mg/m² day or 20- or 25 mg/m² per day from day1 to day 3) + ifosfamide (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices of a 21-days cycle for up to 3 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).
arm group label: Arm B
arm group type: Experimental
description: Experimental-Arm phase III high-risk CINSARC:
Patients will be treated by doxorubicin (60 or 75mg/m² day or 20 or 25 mg/m² per day from day1 to day 3) + ifosfamide (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices of a 21-days cycle for up to 6 cycles in neoadjuvant setting Neoadjuvant chemotherapy will be followed by surgery. If indicated, radiotherapy could be prescribed at the discretion of the investigator (in neoadjuvant or adjuvant setting).
arm group label: Prospective cohort
arm group type: Experimental
description: Patients will be treated at the discretion of the investigator
intervention type: Drug
intervention name: Doxorubicin
description: A treatment cycle consists of 3 weeks. Doxorubicin will be administered from day 1 to day 3 (60 or 75mg/m² day or 20 or 25 mg/m² per day), repeated every 3 weeks, up to 3 cycles.
arm group label: Arm A
intervention type: Drug
intervention name: Ifosfamide or dacarbazine
description: A treatment cycle consists of 3 weeks. Treatment may continue up to 3 cycles. Ifosfamide will be administered from day 1 to day 3 (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices, repeated every 3 weeks, up to 3 cycles.
arm group label: Arm A
intervention type: Drug
intervention name: Doxorubicin
description: A treatment cycle consists of 3 weeks. Doxorubicin will be administered from day 1 to day 3 (60 or 75mg/m² day or 20 or 25 mg/m² per day), repeated every 3 weeks, up to 6 cycles.
arm group label: Arm B
intervention type: Drug
intervention name: Ifosfamide or dacarbazine
description: A treatment cycle consists of 3 weeks. Ifosfamide will be administered from day 1 to day 3 (7,5-9 g/m² over 3 days with mesna and G-CSF) or dacarbazine (100 mg/m² 1 day or 450 mg/m² 2 days) as per local practices, repeated every 3 weeks, up to 6 cycles.
arm group label: Arm B
intervention type: Drug
intervention name: At the discretion of the investigator
description: Drug at the discretion of the investigator.
arm group label: Prospective cohort
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Antoine ITALIANO, MD, PhD
phone: +33 5.56.33.33.33
email: a.italiano@bordeaux.unicancer.fr
last name: Simone MATHOULIN-PELISSIER, MD, PhD
email: m.mathoulin@bordeaux.unicancer.fr
facility: 
status: Recruiting
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status: Not yet recruiting
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country: France
responsible party type: Sponsor
mesh term: Sarcoma
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
mesh term: Ifosfamide
mesh term: Isophosphamide mustard
mesh term: Dacarbazine