<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/NCT04440358</url>
  </required_header>
  <id_info>
    <org_study_id>BT009 [OUS]</org_study_id>
    <nct_id>NCT04440358</nct_id>
  </id_info>
  <brief_title>Exablate Blood-Brain Barrier Disruption With Carboplatin for the Treatment of rGBM</brief_title>
  <official_title>Assessment of Safety and Feasibility of Exablate Blood-Brain Barrier Disruption (BBBD) With Microbubbles for the Treatment of Recurrent Glioblastoma (rGBM) in Subjects Undergoing Carboplatin Monotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>InSightec</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>InSightec</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 purpose of this study is to evaluate the safety and feasibility of the Exablate Model&#xD;
      4000 Type 2 system when used as a tool to open the blood-brain-barrier (BBB) in subjects with&#xD;
      recurrent glioblastoma (rGBM) undergoing carboplatin monotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1/2, open-label, prospective, multi-center, single-arm study to establish the&#xD;
      safety and feasibility of blood-brain-barrier disruption (BBBD) combined with intravenous&#xD;
      carboplatin for the treatment of rGBM using the Exablate Neuro Model 4000 Type 2 system.&#xD;
      Adult glioblastoma subjects that are planned for carboplatin chemotherapy will be considered&#xD;
      for study enrollment. Eligible subjects will undergo up to 6 cycles of Exablate BBBD&#xD;
      procedures in conjunction with carboplatin chemotherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 13, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">July 2023</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>Occurrence of Adverse Events</measure>
    <time_frame>Through study completion, an average of 12 months</time_frame>
    <description>All adverse events and/or Serious Adverse Events will be documented and reported according to CTCAE criteria</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Contrast intensity on MR imaging</measure>
    <time_frame>Immediately after Exablate BBBD procedure</time_frame>
    <description>BBBD will be determined by contrast intensity in sonicated areas on T1 weighted gadolinium-based MR imaging</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Recurrent Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Exablate BBBD with carboplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Carboplatin will be administered via IV infusion about every 4 weeks for up to 6 cycles. The dosage will be calculated based on subject's creatinine level. On the day of planned carboplatin therapy, subjects will undergo Exablate procedure to open the blood-brain-barrier in the targeted cancerous brain areas prior to carboplatin administration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Exablate BBBD</intervention_name>
    <description>BBB opening via Exablate Neuro Type 2 system to deliver carboplatin</description>
    <arm_group_label>Exablate BBBD with carboplatin</arm_group_label>
    <other_name>Exablate Neuro</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin infusion on the day of Exablate BBBD procedure to treat cancerous cells in the brain</description>
    <arm_group_label>Exablate BBBD with carboplatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must be between 18-80 years old&#xD;
&#xD;
          -  Histologically confirmed glioblastoma&#xD;
&#xD;
          -  Planned for Carboplatin monotherapy&#xD;
&#xD;
          -  Be willing and able to provided written informed consent/assent&#xD;
&#xD;
          -  Tumor progression after first line therapy&#xD;
&#xD;
          -  Recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic&#xD;
             effects of prior therapy&#xD;
&#xD;
          -  Women of childbearing potential is confirmed not pregnant. Male and Female subjects&#xD;
             utilize highly effective contraception&#xD;
&#xD;
          -  Able to communicate verbally&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute intracranial hemorrhage&#xD;
&#xD;
          -  Ferrous metallic implanted objects in the skull or brain&#xD;
&#xD;
          -  Prior toxicity with carboplatin chemotherapy&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding&#xD;
&#xD;
          -  Cerebellar spinal cord or brain stem tumor&#xD;
&#xD;
          -  Known active Hepatitis B or Hepatitis C or HIV&#xD;
&#xD;
          -  Significant depression not adequately controlled&#xD;
&#xD;
          -  Cardiac disease or unstable hemodynamics&#xD;
&#xD;
          -  Severe hypertension&#xD;
&#xD;
          -  History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor&#xD;
             hemorrhage&#xD;
&#xD;
          -  Active drug or alcohol use disorder&#xD;
&#xD;
          -  Known sensitivity to gadolinium-based contrast agents&#xD;
&#xD;
          -  Known sensitivity or contraindications to ultrasound contrast agent or perflutren&#xD;
&#xD;
          -  Unable to undergo MRI or contraindications to MRI such as non-MRI compatible implanted&#xD;
             devices&#xD;
&#xD;
          -  Difficulty lying supine and still or severe claustrophobia which cannot be managed&#xD;
             with medication&#xD;
&#xD;
          -  Severely impaired renal function&#xD;
&#xD;
          -  Right to left or bi-directional cardiac shunt&#xD;
&#xD;
          -  Cranial or systemic infection requiring antibiotics&#xD;
&#xD;
          -  Known additional malignancy that is progression or require active treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Neurologico Carlo Besta</name>
      <address>
        <city>Milano</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yonsei University Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
  </location_countries>
  <removed_countries>
    <country>Israel</country>
  </removed_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 17, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>January 3, 2023</last_update_submitted>
  <last_update_submitted_qc>January 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Exablate</keyword>
  <keyword>Focused Ultrasound</keyword>
  <keyword>Carboplatin</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/NCT04440358
org study id: BT009 [OUS]
nct id: NCT04440358
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the safety and feasibility of the Exablate Model
      4000 Type 2 system when used as a tool to open the blood-brain-barrier (BBB) in subjects with
      recurrent glioblastoma (rGBM) undergoing carboplatin monotherapy.
This is a Phase 1/2, open-label, prospective, multi-center, single-arm study to establish the
      safety and feasibility of blood-brain-barrier disruption (BBBD) combined with intravenous
      carboplatin for the treatment of rGBM using the Exablate Neuro Model 4000 Type 2 system.
      Adult glioblastoma subjects that are planned for carboplatin chemotherapy will be considered
      for study enrollment. Eligible subjects will undergo up to 6 cycles of Exablate BBBD
      procedures in conjunction with carboplatin chemotherapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of Adverse Events
time frame: Through study completion, an average of 12 months
description: All adverse events and/or Serious Adverse Events will be documented and reported according to CTCAE criteria
measure: Contrast intensity on MR imaging
time frame: Immediately after Exablate BBBD procedure
description: BBBD will be determined by contrast intensity in sonicated areas on T1 weighted gadolinium-based MR imaging
arm group label: Exablate BBBD with carboplatin
arm group type: Experimental
description: Carboplatin will be administered via IV infusion about every 4 weeks for up to 6 cycles. The dosage will be calculated based on subject's creatinine level. On the day of planned carboplatin therapy, subjects will undergo Exablate procedure to open the blood-brain-barrier in the targeted cancerous brain areas prior to carboplatin administration.
intervention type: Device
intervention name: Exablate BBBD
description: BBB opening via Exablate Neuro Type 2 system to deliver carboplatin
arm group label: Exablate BBBD with carboplatin
other name: Exablate Neuro
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin infusion on the day of Exablate BBBD procedure to treat cancerous cells in the brain
arm group label: Exablate BBBD with carboplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
facility: 
facility: 
country: Canada
country: Italy
country: Korea, Republic of
country: Israel
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Carboplatin