<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/NCT03818386</url>
  </required_header>
  <id_info>
    <org_study_id>38RC18.085</org_study_id>
    <nct_id>NCT03818386</nct_id>
  </id_info>
  <brief_title>Radiotherapy of Multiple Brain Metastases Using AGuIX®</brief_title>
  <acronym>NANORAD2</acronym>
  <official_title>Radiotherapy of Multiple Brain Metastases Using AGuIX® Gadolinium-chelated Polysiloxane Based Nanoparticles: a Prospective Randomized Phase II Clinical Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Grenoble</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NH TherAguix SAS</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Grenoble</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>
      This is a Prospective Randomized Open Blinded Endpoint phase II clinical trial. The study&#xD;
      will be adaptive: an interim analysis is planned after enrolment of 20 patients in each arm&#xD;
      of treatment (WBRT and AGuIX® + WBRT), to select and continue the study with group(s) that&#xD;
      present the best response rate to the experimental treatment (AGuIX® + WBRT).&#xD;
&#xD;
      The main endpoint will be evaluated by a blinded endpoint committee.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The occurrence of brain metastases is a common event in the history of cancer and negatively&#xD;
      affects the life expectancy of patients. Their incidence varies between 15 and 50% according&#xD;
      to the histologic types. Surgery, stereotactic radiosurgery, radiotherapy and chemotherapy&#xD;
      are the main treatments currently proposed.&#xD;
&#xD;
      For patients with multiple brain metastases, whole brain radiation therapy (WBRT) remains the&#xD;
      standard of care. However, the median overall survival is less than 6 months and new&#xD;
      approaches need to be developed to improve treatment of these patients.&#xD;
&#xD;
      In this context, the weak control of the disease comes from three main factors: the&#xD;
      multiplicity of the brain lesions, the radioresistance of certain histologies and the poor&#xD;
      distribution of cytotoxic agents in brain metastases.&#xD;
&#xD;
      The use of radiosensitizing agents is here of great interest. The radiosensitizing agent&#xD;
      chosen in this study is AGuIX®. It is a Gadolinium-chelated polysiloxane based nanoparticle&#xD;
      developed by NH TherAguix company for its theranostic properties (radiosensitization and&#xD;
      diagnosis by multimodal imaging). Preclinical studies have demonstrated the radiosensitizing&#xD;
      effect of AGuIX® in vivo in 8 tumor models xenografted in rodents, and particularly in brain&#xD;
      tumors.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 26, 2019</start_date>
  <completion_date type="Anticipated">March 26, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 26, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Prospective Randomized Open Blinded Endpoint phase II clinical trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The main endpoint will be evaluated by a blinded endpoint committee.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Best objective intracranial response rate - intent-to-treat</measure>
    <time_frame>at 6 weeks</time_frame>
    <description>Evaluation of brain metastases response, according to RECIST v1.1 criteria (or modified RECIST) by MRI, with MRI centralized reading</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Best objective intracranial response rate - intent-to-treat</measure>
    <time_frame>at 3 months</time_frame>
    <description>Evaluation of brain metastases response, according to RECIST v1.1 criteria (or modified RECIST) by MRI, with MRI centralized reading</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the quality of life</measure>
    <time_frame>at D0, 6 weeks, 3, 6, 9, 12 months</time_frame>
    <description>Quality of life test score EORTC QLQ C30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the quality of life</measure>
    <time_frame>at day 0, 6 weeks, 3, 6, 9, 12 months</time_frame>
    <description>Quality of life test score EORTC QLQ BN20</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurocognitive evaluation</measure>
    <time_frame>at Day 0, 6 weeks, 3, 6, 9, 12 months</time_frame>
    <description>Neurocognitive test (MoCA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best objective intracranial response rate - per-protocol</measure>
    <time_frame>at 6 weeks and 3 months</time_frame>
    <description>Evaluation of brain metastases response on per-protocol population, according to RECIST v1.1 criteria (or modified RECIST), by MRI with centralized reading</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the intracranial response rate</measure>
    <time_frame>for 12 months</time_frame>
    <description>Evaluation of brain metastases response, according to RANO, to RECIST v1.1 criteria, and as the evolution of the sum of longest diameters (for all metastases with a sum of diameters &gt; 1cm), by MRI, at 6 weeks and 3, 6, 9 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of individual metastasis response</measure>
    <time_frame>at 6 weeks and 3, 6, 9 and 12 months</time_frame>
    <description>Evaluation of individual brain metastasis response, for all metastases with the sum of diameters &gt; 1cm, by MRI rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intracranial progression-free survival</measure>
    <time_frame>at 12 months</time_frame>
    <description>Evaluation of the time between the start of the treatment and the occurence of intracranial progression or neuriologic death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intracranial progression-free survival, brain survival</measure>
    <time_frame>at 12 months</time_frame>
    <description>Death related to brain metastases progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>at 12 months</time_frame>
    <description>Death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in steroid dependence</measure>
    <time_frame>at 6 weeks and 3, 6, 9 and 12 months</time_frame>
    <description>Reporting of daily steroid dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>at 6 weeks and 3, 6, 9 and 12 months</time_frame>
    <description>Reporting of adverse events by type, frequency and severity for both treatments (WBRT and AGuIX® + WBRT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRI study of the distribution of the product in brain metastases</measure>
    <time_frame>Day 0</time_frame>
    <description>MRI evaluation of contrast enhancement at D0 after AGuIX® injection</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Brain Metastases, Adult</condition>
  <condition>Radiotherapy</condition>
  <arm_group>
    <arm_group_label>AGuIX® + Whole Brain Radiation Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention: Drug: AGuIX® + WBRT&#xD;
Other Names:&#xD;
Gadolinium-chelated polysiloxane based nanoparticles&#xD;
3 intravenous injections at 100mg/kg&#xD;
D0: AGuIX® injection followed by MRI (within 7 days before commencement of WBRT)&#xD;
Fr1: AGuIX® injection before the first radiation session&#xD;
Fr6: AGuIX® injection before the sixth radiation session&#xD;
30 Gy in 10 fractions of 3 Gy over 2-3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Whole Brain Radiation Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intervention: Radiation: Whole Brain Radiation Therapy ( WBRT) 30 Gy in 10 fractions of 3 Gy over 2-3 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AGuIX®</intervention_name>
    <description>3 intravenous injection at 100mg/kg&#xD;
D0: AGuIX® injection followed by MRI (within 7 days before commencement of WBRT)&#xD;
Fr1: AGuIX® injection before the first radiation session&#xD;
Fr6: AGuIX® injection before the sixth radiation session</description>
    <arm_group_label>AGuIX® + Whole Brain Radiation Therapy</arm_group_label>
    <other_name>Gadolinium-chelated polysiloxane based nanoparticles</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Whole Brain Radiation Therapy</intervention_name>
    <description>30 Gy in 10 fractions of 3 Gy over 2-3 weeks</description>
    <arm_group_label>AGuIX® + Whole Brain Radiation Therapy</arm_group_label>
    <arm_group_label>Whole Brain Radiation Therapy</arm_group_label>
    <other_name>WBRT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with brain metastases, from a histologically confirmed solid tumor, eligible&#xD;
             for WBRT&#xD;
&#xD;
          -  At least 18 years old&#xD;
&#xD;
          -  Signed informed consent after informing the patient&#xD;
&#xD;
          -  ECOG (Eastern Cooperative Oncology Group) performance status 0-2&#xD;
&#xD;
          -  Extracranial disease:&#xD;
&#xD;
               -  Complete or partial response or stability under systemic treatment&#xD;
&#xD;
               -  No extracranial disease&#xD;
&#xD;
               -  Or first line of treatment&#xD;
&#xD;
          -  Life expectancy greater than 6 weeks&#xD;
&#xD;
          -  Effective contraceptive method for all patient of childbearing potential&#xD;
&#xD;
          -  Affiliated to a social security regimen&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Leptomeningeal metastasis&#xD;
&#xD;
          -  Evidence of metastasis with recent large hemorrhage&#xD;
&#xD;
          -  Progressive and threatening extracranial disease under systemic treatment&#xD;
&#xD;
          -  Previous cranial irradiation (except stereotactic irradiation)&#xD;
&#xD;
          -  Known contra-indication, sensitivity or allergy to gadolinium&#xD;
&#xD;
          -  Known contra-indication for Magnetic Resonance Imaging&#xD;
&#xD;
          -  Renal insufficiency (glomerular filtration rate ≤ 50 mL/min/1.73m²)&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Subject under administrative or judicial control&#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>Camille VERRY, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Grenoble</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Camille VERRY, MD</last_name>
    <phone>+33 (0)4 76 76 54 35</phone>
    <email>cverry@chu-grenoble.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tinaïg LE COSTAOUEC</last_name>
    <phone>+33 (0)4 76 76 68 13</phone>
    <email>TLecostaouec@chu-grenoble.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Institut Régional du Cancer</name>
      <address>
        <city>Montpellier</city>
        <state>Occitanie</state>
        <zip>34298</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olivier RIOU, Dr</last_name>
      <phone>+33 (0)4 67 61 24 43</phone>
      <email>Olivier.Riou@icm.unicancer.fr</email>
    </contact>
    <contact_backup>
      <last_name>Justine ROCHER, Study Co</last_name>
      <phone>+33 4 67 61 23 71</phone>
      <email>justine.rochet@icm.unicancer.fr</email>
    </contact_backup>
    <investigator>
      <last_name>OLIVIER RIOU, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Claudius Regaud Institut Universitaire du Cancer Toulouse Oncopole Radiothérapie</name>
      <address>
        <city>Toulouse</city>
        <state>Occitanie</state>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ciprian CHIRA</last_name>
      <phone>+33 (0)5 31 15 60 50</phone>
      <email>chira.ciprian@iuct-oncopole.fr</email>
    </contact>
    <contact_backup>
      <last_name>Stella MANTA, Study Co</last_name>
      <phone>05 31 15 58 01</phone>
      <email>manta.stella@iuct-oncopole.fs</email>
    </contact_backup>
    <investigator>
      <last_name>CIPRIAN CHIRA</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Leon Berard Lyon</name>
      <address>
        <city>Lyon</city>
        <state>Rhones Alpes</state>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ronan TANGUY</last_name>
      <phone>+33(0)4 78 78 28 28</phone>
      <email>Ronan.TANGUY@lyon.unicancer.fr</email>
    </contact>
    <contact_backup>
      <last_name>Cécile BACHELIER, Study Co</last_name>
      <phone>+33(0)4 78 78 28 85</phone>
      <email>Cecile.BACHELIER@lyon.unicancer.fr</email>
    </contact_backup>
    <investigator>
      <last_name>RONAN TANGUY</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Annecy Genevois</name>
      <address>
        <city>Annecy</city>
        <state>Rhones-Alpes</state>
        <zip>74374</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexandre TESSIER, MD</last_name>
      <phone>04 50 63 63 63</phone>
      <phone_ext>585380</phone_ext>
      <email>atessier@ch-annecygenevois.fr</email>
    </contact>
    <contact_backup>
      <last_name>Fanny BOCHE, Study Co</last_name>
      <phone>+33 4 56 49 74 69</phone>
      <email>fboche@ch-annecygenevois.fr</email>
    </contact_backup>
    <investigator>
      <last_name>ALEXANDRE TESSIER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>JOHAN KRISTIANSEN, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire Grenoble-Alpes</name>
      <address>
        <city>Grenoble</city>
        <state>Rhones-Alpes</state>
        <zip>38700</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Camille VERRY, MD, PHD</last_name>
      <phone>+33476765435</phone>
      <email>cverry@chu-grenoble.fr</email>
    </contact>
    <contact_backup>
      <last_name>Mélanie GATALETA, Study Co</last_name>
      <phone>+33476768339</phone>
      <email>MGataleta1@chu-grenoble.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Camille VERRY, MD, PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Julie VILLA</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Andréa DESAGNEAUX</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CRLCC - Institut Bergonié</name>
      <address>
        <city>Bordeaux</city>
        <zip>33000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nicolas MILHADE, MD PHD</last_name>
      <email>n.milhade@bordeaux.unicancer.fr</email>
    </contact>
    <contact_backup>
      <last_name>Laurence VIRMOUX, Study Co</last_name>
      <phone>05 56 33 33 33</phone>
      <phone_ext>3531</phone_ext>
      <email>l.virmoux@bordeaux.unicancer.fr</email>
    </contact_backup>
    <investigator>
      <last_name>NICOLAS MILHADE, MD PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Crlcc Francois Baclesse</name>
      <address>
        <city>Caen</city>
        <zip>14000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paul LESUEUR, PHD</last_name>
      <email>p.lesueur@baclesse.unicancer.fr</email>
    </contact>
    <contact_backup>
      <last_name>Bérénice LEGRAND, Study Co</last_name>
      <phone>02 31 45 50 50</phone>
      <email>b.legrand@baclesse.unicancer.fr</email>
    </contact_backup>
    <investigator>
      <last_name>PAUL LESUEUR, MD</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>Gilles TRUC, PUPH</last_name>
      <phone>03 80 73 75 18</phone>
      <email>gtruc@cgfl.fr</email>
    </contact>
    <contact_backup>
      <last_name>Philippe BATAILLARD, Study Co</last_name>
      <email>PBataillard@cgfl.fr</email>
    </contact_backup>
    <investigator>
      <last_name>GILLES TRUC, PUPH</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospices Civils de Lyon-Hôpital Lyon Sud</name>
      <address>
        <city>Lyon</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anne D'HOMBRES</last_name>
      <email>anne.dhombres@chu-lyon.fr</email>
    </contact>
    <contact_backup>
      <last_name>Célia PREVOST, Study Co</last_name>
      <phone>04 78 86 42 99</phone>
      <email>celia.prevost@chu-lyon.fr</email>
    </contact_backup>
    <investigator>
      <last_name>ANNE D'HOMBRES</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Européen Georges Pompidou</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Philippe GIRAUD, MD, PHD</last_name>
      <phone>01 56 09 54 65</phone>
      <email>philippe.giraud@aphp.fr</email>
    </contact>
    <contact_backup>
      <last_name>Virginie RIEB, Study Co</last_name>
      <phone>01 56 09 50 09</phone>
      <email>virginie.rieb@aphp.fr</email>
    </contact_backup>
    <investigator>
      <last_name>PHILIPPE GIRAUD, MD, PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>La Pitié Salpêtrière - Charles Foix</name>
      <address>
        <city>Paris</city>
        <zip>75651</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Julian JACOB, MD, PHD</last_name>
      <phone>+33 (0) 1 42 17 81 71</phone>
      <email>julian.jacob@aphp.fr</email>
    </contact>
    <contact_backup>
      <last_name>Audie BAVOUIDIBIO, Study Co</last_name>
      <phone>+33 (0) 1 42 16 00 25</phone>
      <email>audie.bavouidibio2@aphp.fr</email>
    </contact_backup>
    <investigator>
      <last_name>JULIAN JACOB, MD, PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Curie Saint Cloud</name>
      <address>
        <city>Saint-Cloud</city>
        <zip>92210</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maxime LOO</last_name>
      <email>maxime.loo@curie.fr</email>
    </contact>
    <contact_backup>
      <last_name>Agnès BABARIT, Study Co</last_name>
      <phone>+33(0) 1 47 11 18 55</phone>
      <email>agnes.babarit@curie.fr</email>
    </contact_backup>
    <investigator>
      <last_name>MAXIME LOO</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Crlcc Paul Strauss</name>
      <address>
        <city>Strasbourg</city>
        <zip>67085</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>George NOEL, MD PHD</last_name>
      <email>gnoel@strasbourg.unicancer.fr</email>
    </contact>
    <contact_backup>
      <last_name>Laurence KLEIDER, Study Co</last_name>
      <phone>03 68 76 73 60</phone>
      <email>l.kleider@icans.eu</email>
    </contact_backup>
    <investigator>
      <last_name>GEORGE NOEL, MD PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de Lorraine ALEXIS VAUTRIN</name>
      <address>
        <city>Vandœuvre-lès-Nancy</city>
        <zip>54519</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anaïs STEFANI, MD</last_name>
      <phone>03 83 59 84 27</phone>
      <email>a.stefani@nancy.unicancer.fr</email>
    </contact>
    <contact_backup>
      <last_name>Fabienne BONNICHON, Study Co</last_name>
      <phone>03 83 59 84 27</phone>
      <phone_ext>87 23</phone_ext>
      <email>f.polet@nancy.unicancer.fr</email>
    </contact_backup>
    <investigator>
      <last_name>ANAIS STEFANI, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Le Duc G, Miladi I, Alric C, Mowat P, Brauer-Krisch E, Bouchet A, Khalil E, Billotey C, Janier M, Lux F, Epicier T, Perriat P, Roux S, Tillement O. Toward an image-guided microbeam radiation therapy using gadolinium-based nanoparticles. ACS Nano. 2011 Dec 27;5(12):9566-74. doi: 10.1021/nn202797h. Epub 2011 Nov 9.</citation>
    <PMID>22040385</PMID>
  </reference>
  <reference>
    <citation>Lux F, Tran VL, Thomas E, Dufort S, Rossetti F, Martini M, Truillet C, Doussineau T, Bort G, Denat F, Boschetti F, Angelovski G, Detappe A, Cremillieux Y, Mignet N, Doan BT, Larrat B, Meriaux S, Barbier E, Roux S, Fries P, Muller A, Abadjian MC, Anderson C, Canet-Soulas E, Bouziotis P, Barberi-Heyob M, Frochot C, Verry C, Balosso J, Evans M, Sidi-Boumedine J, Janier M, Butterworth K, McMahon S, Prise K, Aloy MT, Ardail D, Rodriguez-Lafrasse C, Porcel E, Lacombe S, Berbeco R, Allouch A, Perfettini JL, Chargari C, Deutsch E, Le Duc G, Tillement O. AGuIX(R) from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine. Br J Radiol. 2019 Jan;92(1093):20180365. doi: 10.1259/bjr.20180365. Epub 2018 Sep 18.</citation>
    <PMID>30226413</PMID>
  </reference>
  <reference>
    <citation>Verry C, Dufort S, Barbier EL, Montigon O, Peoc'h M, Chartier P, Lux F, Balosso J, Tillement O, Sancey L, Le Duc G. MRI-guided clinical 6-MV radiosensitization of glioma using a unique gadolinium-based nanoparticles injection. Nanomedicine (Lond). 2016 Sep;11(18):2405-17. doi: 10.2217/nnm-2016-0203. Epub 2016 Aug 16.</citation>
    <PMID>27529506</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>August 16, 2023</last_update_submitted>
  <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>gadolinium nanoparticles</keyword>
  <keyword>AGuIX</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
  </condition_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/NCT03818386
org study id: 38RC18.085
nct id: NCT03818386
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a Prospective Randomized Open Blinded Endpoint phase II clinical trial. The study
      will be adaptive: an interim analysis is planned after enrolment of 20 patients in each arm
      of treatment (WBRT and AGuIX® + WBRT), to select and continue the study with group(s) that
      present the best response rate to the experimental treatment (AGuIX® + WBRT).

      The main endpoint will be evaluated by a blinded endpoint committee.
The occurrence of brain metastases is a common event in the history of cancer and negatively
      affects the life expectancy of patients. Their incidence varies between 15 and 50% according
      to the histologic types. Surgery, stereotactic radiosurgery, radiotherapy and chemotherapy
      are the main treatments currently proposed.

      For patients with multiple brain metastases, whole brain radiation therapy (WBRT) remains the
      standard of care. However, the median overall survival is less than 6 months and new
      approaches need to be developed to improve treatment of these patients.

      In this context, the weak control of the disease comes from three main factors: the
      multiplicity of the brain lesions, the radioresistance of certain histologies and the poor
      distribution of cytotoxic agents in brain metastases.

      The use of radiosensitizing agents is here of great interest. The radiosensitizing agent
      chosen in this study is AGuIX®. It is a Gadolinium-chelated polysiloxane based nanoparticle
      developed by NH TherAguix company for its theranostic properties (radiosensitization and
      diagnosis by multimodal imaging). Preclinical studies have demonstrated the radiosensitizing
      effect of AGuIX® in vivo in 8 tumor models xenografted in rodents, and particularly in brain
      tumors.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective Randomized Open Blinded Endpoint phase II clinical trial.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The main endpoint will be evaluated by a blinded endpoint committee.
measure: Best objective intracranial response rate - intent-to-treat
time frame: at 6 weeks
description: Evaluation of brain metastases response, according to RECIST v1.1 criteria (or modified RECIST) by MRI, with MRI centralized reading
measure: Best objective intracranial response rate - intent-to-treat
time frame: at 3 months
description: Evaluation of brain metastases response, according to RECIST v1.1 criteria (or modified RECIST) by MRI, with MRI centralized reading
measure: Evaluation of the quality of life
time frame: at D0, 6 weeks, 3, 6, 9, 12 months
description: Quality of life test score EORTC QLQ C30
measure: Evaluation of the quality of life
time frame: at day 0, 6 weeks, 3, 6, 9, 12 months
description: Quality of life test score EORTC QLQ BN20
measure: Neurocognitive evaluation
time frame: at Day 0, 6 weeks, 3, 6, 9, 12 months
description: Neurocognitive test (MoCA)
measure: Best objective intracranial response rate - per-protocol
time frame: at 6 weeks and 3 months
description: Evaluation of brain metastases response on per-protocol population, according to RECIST v1.1 criteria (or modified RECIST), by MRI with centralized reading
measure: Evaluation of the intracranial response rate
time frame: for 12 months
description: Evaluation of brain metastases response, according to RANO, to RECIST v1.1 criteria, and as the evolution of the sum of longest diameters (for all metastases with a sum of diameters > 1cm), by MRI, at 6 weeks and 3, 6, 9 and 12 months
measure: Evaluation of individual metastasis response
time frame: at 6 weeks and 3, 6, 9 and 12 months
description: Evaluation of individual brain metastasis response, for all metastases with the sum of diameters > 1cm, by MRI rate
measure: Intracranial progression-free survival
time frame: at 12 months
description: Evaluation of the time between the start of the treatment and the occurence of intracranial progression or neuriologic death
measure: Intracranial progression-free survival, brain survival
time frame: at 12 months
description: Death related to brain metastases progression
measure: Overall survival
time frame: at 12 months
description: Death
measure: Change in steroid dependence
time frame: at 6 weeks and 3, 6, 9 and 12 months
description: Reporting of daily steroid dose
measure: Incidence of adverse events
time frame: at 6 weeks and 3, 6, 9 and 12 months
description: Reporting of adverse events by type, frequency and severity for both treatments (WBRT and AGuIX® + WBRT)
measure: MRI study of the distribution of the product in brain metastases
time frame: Day 0
description: MRI evaluation of contrast enhancement at D0 after AGuIX® injection
arm group label: AGuIX® + Whole Brain Radiation Therapy
arm group type: Experimental
description: Intervention: Drug: AGuIX® + WBRT
Other Names:
Gadolinium-chelated polysiloxane based nanoparticles
3 intravenous injections at 100mg/kg
D0: AGuIX® injection followed by MRI (within 7 days before commencement of WBRT)
Fr1: AGuIX® injection before the first radiation session
Fr6: AGuIX® injection before the sixth radiation session
30 Gy in 10 fractions of 3 Gy over 2-3 weeks
arm group label: Whole Brain Radiation Therapy
arm group type: Active Comparator
description: Intervention: Radiation: Whole Brain Radiation Therapy ( WBRT) 30 Gy in 10 fractions of 3 Gy over 2-3 weeks
intervention type: Drug
intervention name: AGuIX®
description: 3 intravenous injection at 100mg/kg
D0: AGuIX® injection followed by MRI (within 7 days before commencement of WBRT)
Fr1: AGuIX® injection before the first radiation session
Fr6: AGuIX® injection before the sixth radiation session
arm group label: AGuIX® + Whole Brain Radiation Therapy
other name: Gadolinium-chelated polysiloxane based nanoparticles
intervention type: Radiation
intervention name: Whole Brain Radiation Therapy
description: 30 Gy in 10 fractions of 3 Gy over 2-3 weeks
arm group label: AGuIX® + Whole Brain Radiation Therapy
arm group label: Whole Brain Radiation Therapy
other name: WBRT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Camille VERRY, MD
role: Principal Investigator
affiliation: University Hospital, Grenoble
last name: Camille VERRY, MD
phone: +33 (0)4 76 76 54 35
email: cverry@chu-grenoble.fr
last name: Tinaïg LE COSTAOUEC
phone: +33 (0)4 76 76 68 13
email: TLecostaouec@chu-grenoble.fr
facility: 
status: Recruiting
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country: France
citation: Le Duc G, Miladi I, Alric C, Mowat P, Brauer-Krisch E, Bouchet A, Khalil E, Billotey C, Janier M, Lux F, Epicier T, Perriat P, Roux S, Tillement O. Toward an image-guided microbeam radiation therapy using gadolinium-based nanoparticles. ACS Nano. 2011 Dec 27;5(12):9566-74. doi: 10.1021/nn202797h. Epub 2011 Nov 9.
PMID: 22040385
citation: Lux F, Tran VL, Thomas E, Dufort S, Rossetti F, Martini M, Truillet C, Doussineau T, Bort G, Denat F, Boschetti F, Angelovski G, Detappe A, Cremillieux Y, Mignet N, Doan BT, Larrat B, Meriaux S, Barbier E, Roux S, Fries P, Muller A, Abadjian MC, Anderson C, Canet-Soulas E, Bouziotis P, Barberi-Heyob M, Frochot C, Verry C, Balosso J, Evans M, Sidi-Boumedine J, Janier M, Butterworth K, McMahon S, Prise K, Aloy MT, Ardail D, Rodriguez-Lafrasse C, Porcel E, Lacombe S, Berbeco R, Allouch A, Perfettini JL, Chargari C, Deutsch E, Le Duc G, Tillement O. AGuIX(R) from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine. Br J Radiol. 2019 Jan;92(1093):20180365. doi: 10.1259/bjr.20180365. Epub 2018 Sep 18.
PMID: 30226413
citation: Verry C, Dufort S, Barbier EL, Montigon O, Peoc'h M, Chartier P, Lux F, Balosso J, Tillement O, Sancey L, Le Duc G. MRI-guided clinical 6-MV radiosensitization of glioma using a unique gadolinium-based nanoparticles injection. Nanomedicine (Lond). 2016 Sep;11(18):2405-17. doi: 10.2217/nnm-2016-0203. Epub 2016 Aug 16.
PMID: 27529506
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
sharing ipd: No