<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/NCT02253212</url>
  </required_header>
  <id_info>
    <org_study_id>P120905</org_study_id>
    <secondary_id>2014-000393-19</secondary_id>
    <nct_id>NCT02253212</nct_id>
  </id_info>
  <brief_title>Safety of BBB Opening With the SonoCloud</brief_title>
  <acronym>SONOCLOUD</acronym>
  <official_title>A Study to Evaluate the Safety of Transient Opening of the Blood-Brain Barrier by Low Intensity Pulsed Ultrasound With the SonoCloud Implantable Device in Patients With Recurrent Glioblastoma Before Chemotherapy Administration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      PURPOSE: The purpose of this study is to determine whether transient opening of the&#xD;
      blood-brain barrier by pulsed ultrasound using the SonoCloud implantable ultrasound device is&#xD;
      safely tolerated in patients with recurrent glioblastoma immediately before systemic delivery&#xD;
      of carboplatin-based chemotherapy.&#xD;
&#xD;
      STUDY HYPOTHESIS: The blood-brain barrier can be safely opened using pulsed ultrasound prior&#xD;
      to chemotherapy administration in patients with recurrent glioblastoma. Transient opening of&#xD;
      the blood-brain barrier by pulsed ultrasound will increase the glioblastoma exposure to&#xD;
      carboplatin-based chemotherapy and increase progression-free and overall survival in patients&#xD;
      with recurrent glioblastoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For patients with recurrent malignant gliomas, who have already been treated by a combination&#xD;
      of surgery, radiation therapy and/or chemotherapy, few treatment options currently exist.&#xD;
      Salvage therapies typically consist of systemic administration of chemotherapy agents, which&#xD;
      have been shown to have limited effectiveness as median survival in this patient group is&#xD;
      currently only 6 months.&#xD;
&#xD;
      One limitation to the efficacy of systemic chemotherapy in the treatment of brain tumors is&#xD;
      the blood-brain barrier (BBB). To enhance the delivery of systemically administered&#xD;
      chemotherapy agents to brain tumors, an implantable ultrasound device was developed that can&#xD;
      be used to temporarily disrupt the BBB. Delivery of pulsed ultrasound, in combination with an&#xD;
      ultrasound contrast agent, has been shown to temporarily disrupt the BBB for a duration of&#xD;
      more than 6 hours and allow for a significantly increased penetration of systemically&#xD;
      administered chemotherapy drugs in pre-clinical studies.&#xD;
&#xD;
      This study will evaluate the safety of temporary disruption of the BBB during carboplatin&#xD;
      chemotherapy delivery in patients with recurrent glioblastoma. This study will also evaluate&#xD;
      the maximum tolerated dose of ultrasound that can be used to disrupt the BBB.&#xD;
&#xD;
      The use of dynamic contrast-enhanced MRI will be evaluated for determining the extent and&#xD;
      magnitude of BBB opening. Clinical efficacy (Survival) and radiological efficacy (Progression&#xD;
      Free Survival) will also be evaluated as secondary endpoints.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Actual">July 2018</completion_date>
  <primary_completion_date type="Actual">July 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety of transient disruption of the blood-brain barrier using the SonoCloud system in patients with recurrent glioblastoma.</measure>
    <time_frame>12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum tolerated dose of ultrasound with the SonoCloud system for transient disruption of the BBB.</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of the disruption of the BBB by the SonoCloud system using dynamic T1 contrast-enhanced MRI.</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival in patients treated with the SonoCloud system in combination with carboplatin chemotherapy.</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival in patients treated with the SonoCloud system in combination with carboplatin chemotherapy.</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Glioblastoma</condition>
  <condition>Glioma</condition>
  <condition>Brain Tumor</condition>
  <arm_group>
    <arm_group_label>SonoCloud + carboplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SonoCloud : dose escalation Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>SonoCloud</intervention_name>
    <description>SonoCloud : dose escalation</description>
    <arm_group_label>SonoCloud + carboplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC</description>
    <arm_group_label>SonoCloud + carboplatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Age greater than 18 years.&#xD;
&#xD;
          -  Subjects with recurrent glioma who have failed standard therapy with surgery and/or&#xD;
             treatment with radiation and temozolomide.&#xD;
&#xD;
          -  Patient eligible for Carboplatin-based chemotherapy&#xD;
&#xD;
          -  Contrast-enhanced tumor less than 35 mm in diameter&#xD;
&#xD;
          -  No risk of cerebral herniation&#xD;
&#xD;
          -  Able to tolerate pre/post procedure steroid treatment&#xD;
&#xD;
          -  Social security affiliated (in France)&#xD;
&#xD;
          -  Able and willing to give signed and informed consent&#xD;
&#xD;
          -  Normal biological status&#xD;
&#xD;
          -  Hemoglobin ≥ 10 g/dl&#xD;
&#xD;
          -  Platelets ≥ 100000/mm3&#xD;
&#xD;
          -  Neutrophils ≥ 1500/mm3&#xD;
&#xD;
          -  Normal creatine clearance ≥ 60ml/mn&#xD;
&#xD;
          -  ASAT &lt; 3 N&#xD;
&#xD;
          -  ALAT &lt; 3 N&#xD;
&#xD;
          -  Normal Bilirubin Level &lt; 1.5 N&#xD;
&#xD;
          -  Alkaline Phosphatase &lt; 3 N&#xD;
&#xD;
          -  INR &lt; 1.5&#xD;
&#xD;
          -  Prothrombin Level ≥ 70%&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Allergic to Iodine, Gadolinium, Xylocain&#xD;
&#xD;
          -  Contra-indications to echographic contrast agent (microbubbles)&#xD;
&#xD;
          -  Severe Renal insufficiency&#xD;
&#xD;
          -  Hepatic insufficiency&#xD;
&#xD;
          -  Possible toxic treatment for CNS&#xD;
&#xD;
          -  Previously infected surgical field&#xD;
&#xD;
          -  Uncontrolled epilepsy&#xD;
&#xD;
          -  MRI contra-indications&#xD;
&#xD;
          -  Hemostasis troubles thrombopenia &lt;75.000, TP &lt;60%, INR &gt;1.5, anti-platelet or&#xD;
             anticoagulant therapy on-going)&#xD;
&#xD;
          -  Active phlebitis or active pulmonary embolism&#xD;
&#xD;
          -  Pregnant or currently breast-feeding&#xD;
&#xD;
          -  Patients under judicial protection&#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>Ahmed Idbaih, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Groupe Hospitalier Pitié Salpetriere - Neurosurgery Department</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <last_update_submitted>October 10, 2018</last_update_submitted>
  <last_update_submitted_qc>October 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Blood brain barrier (BBB)</keyword>
  <keyword>Disruption</keyword>
  <keyword>Low intensity pulsed ultrasound (LIPU)</keyword>
  <keyword>Sonocloud device</keyword>
  <keyword>Glioblastoma (GBM)</keyword>
  <keyword>Brain Cancer</keyword>
  <keyword>Carboplatin</keyword>
  <keyword>Therapeutic Ultrasound</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</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/NCT02253212
org study id: P120905
secondary id: 2014-000393-19
nct id: NCT02253212
lead sponsor: 
has dmc: Yes
PURPOSE: The purpose of this study is to determine whether transient opening of the
      blood-brain barrier by pulsed ultrasound using the SonoCloud implantable ultrasound device is
      safely tolerated in patients with recurrent glioblastoma immediately before systemic delivery
      of carboplatin-based chemotherapy.

      STUDY HYPOTHESIS: The blood-brain barrier can be safely opened using pulsed ultrasound prior
      to chemotherapy administration in patients with recurrent glioblastoma. Transient opening of
      the blood-brain barrier by pulsed ultrasound will increase the glioblastoma exposure to
      carboplatin-based chemotherapy and increase progression-free and overall survival in patients
      with recurrent glioblastoma.
For patients with recurrent malignant gliomas, who have already been treated by a combination
      of surgery, radiation therapy and/or chemotherapy, few treatment options currently exist.
      Salvage therapies typically consist of systemic administration of chemotherapy agents, which
      have been shown to have limited effectiveness as median survival in this patient group is
      currently only 6 months.

      One limitation to the efficacy of systemic chemotherapy in the treatment of brain tumors is
      the blood-brain barrier (BBB). To enhance the delivery of systemically administered
      chemotherapy agents to brain tumors, an implantable ultrasound device was developed that can
      be used to temporarily disrupt the BBB. Delivery of pulsed ultrasound, in combination with an
      ultrasound contrast agent, has been shown to temporarily disrupt the BBB for a duration of
      more than 6 hours and allow for a significantly increased penetration of systemically
      administered chemotherapy drugs in pre-clinical studies.

      This study will evaluate the safety of temporary disruption of the BBB during carboplatin
      chemotherapy delivery in patients with recurrent glioblastoma. This study will also evaluate
      the maximum tolerated dose of ultrasound that can be used to disrupt the BBB.

      The use of dynamic contrast-enhanced MRI will be evaluated for determining the extent and
      magnitude of BBB opening. Clinical efficacy (Survival) and radiological efficacy (Progression
      Free Survival) will also be evaluated as secondary endpoints.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of transient disruption of the blood-brain barrier using the SonoCloud system in patients with recurrent glioblastoma.
time frame: 12 months
measure: Maximum tolerated dose of ultrasound with the SonoCloud system for transient disruption of the BBB.
time frame: 12 months
measure: Quantification of the disruption of the BBB by the SonoCloud system using dynamic T1 contrast-enhanced MRI.
time frame: 12 months
measure: Progression-free survival in patients treated with the SonoCloud system in combination with carboplatin chemotherapy.
time frame: 12 months
measure: Overall survival in patients treated with the SonoCloud system in combination with carboplatin chemotherapy.
time frame: 12 months
arm group label: SonoCloud + carboplatin
arm group type: Experimental
description: SonoCloud : dose escalation Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC
intervention type: Device
intervention name: SonoCloud
description: SonoCloud : dose escalation
arm group label: SonoCloud + carboplatin
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC
arm group label: SonoCloud + carboplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ahmed Idbaih, MD, PhD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
facility: 
country: France
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Carboplatin