<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/NCT04446416</url>
  </required_header>
  <id_info>
    <org_study_id>NF-2019-01</org_study_id>
    <nct_id>NCT04446416</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of NaviFUS System add-on Bevacizumab (BEV) in Recurrent GBM Patients</brief_title>
  <official_title>An Open Label, Prospective, Pilot Study to Evaluate the Efficacy and Safety of Best Physician's Choice of Standard of Care Combined With NaviFUS System in Patients With Recurrent Glioblastoma Multiforme</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NaviFUS Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>NaviFUS Corporation</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, single-arm, two stages, open-label, pilot study to investigate the&#xD;
      efficacy and safety of FUS add-on bevacizumab (BEV) in rGBM patients. The BEV is the best&#xD;
      physician's choice of standard of care for rGBM after prior radiotherapy and temozolomide&#xD;
      chemotherapy in the LinKou Chang Gung Memorial Hospital. Eligible patients will be enrolled&#xD;
      through the process of informed consent.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This trial will be divided into two stages. The study design and procedures will be as&#xD;
      follows:&#xD;
&#xD;
      Stage 1:&#xD;
&#xD;
      Eligible patients will first be administered with BEV 10 mg/kg intravenous (IV) infusion.&#xD;
      After 30-60 minutes, patients will receive microbubbles (MB) (SonoVue®) 0.1 mL/kg and optimal&#xD;
      ultrasound exposure doses (based on the acoustic emission feedback FUS power control&#xD;
      algorithm) generated from the NaviFUS System single exposure unit for up to two minutes every&#xD;
      2 weeks to transiently open the BBB.&#xD;
&#xD;
      After 4 weeks of treatment with BEV and single unit FUS-MB treatment, if the patient&#xD;
      experienced BBB opening using FUS treatment and BEV IV infusion without any serious adverse&#xD;
      effects (such as brain significant bleeding), then the patient may proceed to stage 2.&#xD;
&#xD;
      Stage 2:&#xD;
&#xD;
      Patients who complete stage 1 will enter stage 2 to receive the BEV with MB-mediated multiple&#xD;
      units of FUS treatment for up to five minutes (but the maximum exposure time per single unit&#xD;
      is two minutes) every 2 weeks for up to 30 weeks or until evidence of progressive disease,&#xD;
      unacceptable toxicity, non-compliance with study follow-up, or withdrawal of consent.&#xD;
&#xD;
      After completion of study treatment, patients will be followed up for 28 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 21, 2020</start_date>
  <completion_date type="Actual">August 4, 2023</completion_date>
  <primary_completion_date type="Actual">September 30, 2022</primary_completion_date>
  <phase>N/A</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>Adverse Event</measure>
    <time_frame>38 weeks</time_frame>
    <description>Number and severity of adverse event</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free survival at 6 months (PFS-6)</measure>
    <time_frame>6 months</time_frame>
    <description>Estimated rate of patients treated during 6 months without experiencing disease</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor shrinkage</measure>
    <time_frame>38 weeks</time_frame>
    <description>The tumor shrinkage rate (TSR) by measuring the longest diameter and perpendicular diameter of the main mass on MRI scans</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>38 weeks</time_frame>
    <description>Proportion of subjects in the analysis population who have complete response (CR) or partial response (PR) using Radiologic Assessment in Neuro-Oncology criteria (RANO) criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PET uptake</measure>
    <time_frame>38 weeks</time_frame>
    <description>The uptake of PET (as standard uptake value - SUV and tumor-to-background ratio - TBR) in tumor and in normal contralateral gray matter before start of BEV+FUS treatment will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>38 weeks</time_frame>
    <description>OS is defined as the time in months from study treatment to death or last follow-up if alive from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of the BBB opening</measure>
    <time_frame>38 weeks</time_frame>
    <description>The FUS with microbubbles can temporally open the BBB. The spatial permeability of the BBB-opened region will be assessed using dynamic contrast-enhanced MRI (DCE-MRI).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Corticosteroid consumption</measure>
    <time_frame>38 weeks</time_frame>
    <description>Increase or decrease in corticosteroid use compared to baseline. The mean corticosteroid dosage prior to study treatment will be considered as the patient's baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (QoL) assessment with the EORTC QLQ-C30</measure>
    <time_frame>38 weeks</time_frame>
    <description>The validated European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30) will be used. The EORTC QLQ-C30 is a 30-item questionnaire. All of the response scale to questions are rated on a 4-point Likert scale from 1 = not at all, 2 = a little, 3 = quite a bit, to 4 = very much, and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (QoL) assessment with the EORTC QLQ-BN20</measure>
    <time_frame>38 weeks</time_frame>
    <description>The EORTC QLQ-BN20 is a QoL assessment specific to brain neoplasms. The questionnaire includes 20 items. All of the response scale to questions are rated on a 4-point Likert scale from 1 = not at all, 2 = a little, 3 = quite a bit, to 4 = very much, and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Glioblastoma Multiforme</condition>
  <condition>Glioblastoma</condition>
  <condition>Glioma</condition>
  <condition>Brain Tumor</condition>
  <condition>Neoplasms</condition>
  <condition>Neoplasms, Nerve Tissue</condition>
  <arm_group>
    <arm_group_label>Bevacizumab plus NaviFUS System</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Device: NaviFUS System BBB Disruption by FUS in recurrent GBM Microbubbles (MB) (SonoVue®) 0.1 mL/kg and optimal ultrasound exposure doses (based on the acoustic emission feedback FUS power control algorithm) generated from the NaviFUS System every 2 weeks to transiently open the BBB.&#xD;
Drug: Bevacizumab 10 mg/kg every 2 weeks for up to 36 weeks or until evidence of progressive disease, unacceptable toxicity, non-compliance with study follow-up, or withdrawal of consent.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>NaviFUS System</intervention_name>
    <description>Open the BBB using focused ultrasound and contrast agent SonoVue®</description>
    <arm_group_label>Bevacizumab plus NaviFUS System</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>An anti-angiogenic agent to block tumor growth</description>
    <arm_group_label>Bevacizumab plus NaviFUS System</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult male/female patients ≥ 20 years of age&#xD;
&#xD;
          2. Patients with histologically confirmed glioblastoma, recurrent after prior&#xD;
             radiotherapy and temozolomide chemotherapy.&#xD;
&#xD;
          3. Patient may have been operated for recurrence. If operated: with measurable residual&#xD;
             tumor&#xD;
&#xD;
          4. Minimum interval since completion of radiation treatment is 12 weeks&#xD;
&#xD;
          5. Patients if already on the steroids then should be on a stable dose of steroids for at&#xD;
             least 7 days prior to study treatment&#xD;
&#xD;
          6. Body mass index (BMI) ≥17 kg / m2&#xD;
&#xD;
          7. Minimum interval since last drug therapy:&#xD;
&#xD;
               -  1 week for non-cytotoxic agents (e.g., interferon, tamoxifen), daily chemotherapy&#xD;
                  (e.g., metronomic temozolomide, cytoxan) or targeted therapies administered daily&#xD;
                  (e.g., gleevec, tarceva)&#xD;
&#xD;
               -  4 weeks since last cytotoxic therapy&#xD;
&#xD;
               -  6 weeks since the completion of a nitrosourea-containing chemotherapy regimen&#xD;
                  (e.g., carmustine (BCNU))&#xD;
&#xD;
          8. Patients with life expectancy ≥ 3 months&#xD;
&#xD;
          9. The Karnofsky performance status (KPS) in the patient must be &gt; 60&#xD;
&#xD;
         10. Eastern Cooperative Oncology Group (ECOG) Score ≤ 2&#xD;
&#xD;
         11. Adequate hepatic, renal, coagulation, and hematopoietic function&#xD;
&#xD;
               -  Hemoglobin ≥ 8 g/dL&#xD;
&#xD;
               -  Platelets ≥ 100,000/mm3&#xD;
&#xD;
               -  Neutrophils ≥ 1,500/mm3&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
               -  Urine protein creatinine (UPC) ratio &lt; 1 or urine dipstick for proteinuria ≤ 2+&#xD;
&#xD;
               -  Alanine transaminase (ALT) &lt; 3 ULN&#xD;
&#xD;
               -  Aspartate transaminase (AST) &lt; 3 x ULN&#xD;
&#xD;
               -  Prothrombin time ≤ 1.2 x ULN&#xD;
&#xD;
               -  International Normalized Ratio (INR) &lt; 1.5&#xD;
&#xD;
               -  Bilirubin &lt; 2 x ULN&#xD;
&#xD;
         12. Patients with the region of interest (ROI) for FUS exposure are located close to the&#xD;
             cortex with at least 20 mm distance beneath the skull bone and the ROI is not in the&#xD;
             deep center brain with crucial brain functions, such as in the region of brain stem,&#xD;
             or motor or speech regions&#xD;
&#xD;
         13. Patients with the potential for pregnancy and their partner must agree to use adequate&#xD;
             contraception or be surgically sterile, or abstain from heterosexual activity starting&#xD;
             with the first dose of treatment through at least 6 months after the last dose of BEV&#xD;
             to avoid conception. Female patients of child-bearing potential must have a negative&#xD;
             pregnancy test. Male patients must agree to use an adequate method of contraception&#xD;
             starting with the first dose of treatment through 6 months after the last dose of BEV.&#xD;
&#xD;
         14. Able to give informed consent for the participation in the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who have had previous treatment with an inhibitor of vascular endothelial&#xD;
             growth factor (VEGF) or VEGFR (including bevacizumab)&#xD;
&#xD;
          2. New York Heart Association (NYHA) Grade II or greater congestive heart failure&#xD;
             requiring hospitalization within 12 months prior to screening&#xD;
&#xD;
          3. Severe hypertension at screening (diastolic blood pressure &gt; 100 mmHg on medication)&#xD;
&#xD;
          4. Uncontrolled intercurrent illness including, but not limited to symptomatic congestive&#xD;
             heart failure, unstable angina pectoris, severe cerebral or myocardial infarction,&#xD;
             cardiac shunt, heart attack within the previous 12 months, stroke (except for&#xD;
             transient ischemic attack; TIA) within the previous 6 months, or psychiatric&#xD;
             illness/social situations that would limit compliance with study requirements&#xD;
&#xD;
          5. Unstable pulmonary disease or Chronic Obstructive Pulmonary Disease exacerbation or&#xD;
             other respiratory illness requiring hospitalization or precluding study therapy at the&#xD;
             time of screening&#xD;
&#xD;
          6. Implanted pacemaker, defibrillator or deep brain stimulator, other implanted&#xD;
             electronic devices in the brain or documented clinically significant arrhythmias&#xD;
&#xD;
          7. Major surgery such as intra-thoracic, intra-abdominal or intra-pelvic (with the&#xD;
             exception of craniotomy), open biopsy or significant traumatic injury ≤ 4 weeks prior&#xD;
             to screening, or patients who have had minor procedures, percutaneous biopsies or&#xD;
             placement of vascular access device ≤ 1 week prior to screening, or who have not&#xD;
             recovered from side effects of such procedure or injury&#xD;
&#xD;
          8. Known HIV positive patients, however, that HIV testing is not required for entry into&#xD;
             this study&#xD;
&#xD;
          9. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of&#xD;
             screening&#xD;
&#xD;
         10. Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within&#xD;
             one week prior to beginning treatment&#xD;
&#xD;
         11. Pregnant or breast-feeding women&#xD;
&#xD;
         12. Known sensitivity/allergy to PET tracers, Magnetic Resonance Imaging (MRI) contrast&#xD;
             agents, Computer Tomography (CT) contrast agents, SonoVue®, bevacizumab, or any of&#xD;
             their components&#xD;
&#xD;
         13. Abnormal baseline findings considered by the investigator to indicate conditions that&#xD;
             might affect study endpoints&#xD;
&#xD;
         14. Patients who have hemorrhage or cyst within the ROI&#xD;
&#xD;
         15. The receipt of an investigational drug within a period of 4 weeks prior to the first&#xD;
             FUS exposure&#xD;
&#xD;
         16. Use of any recreational drugs or history of drug addiction&#xD;
&#xD;
         17. Any other condition that, in the investigator's judgment, might increase the risk to&#xD;
             the patients or decrease the chance of obtaining satisfactory data needed to achieve&#xD;
             the objectives of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kuo-Chen Wei, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chang Gung Memorial Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Linkou Chang Gung Memorial Hospital</name>
      <address>
        <city>Taoyuan City</city>
        <zip>33305</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <reference>
    <citation>Liu HL, Hsu PH, Lin CY, Huang CW, Chai WY, Chu PC, Huang CY, Chen PY, Yang LY, Kuo JS, Wei KC. Focused Ultrasound Enhances Central Nervous System Delivery of Bevacizumab for Malignant Glioma Treatment. Radiology. 2016 Oct;281(1):99-108. doi: 10.1148/radiol.2016152444. Epub 2016 May 18.</citation>
    <PMID>27192459</PMID>
  </reference>
  <reference>
    <citation>Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. doi: 10.1200/JCO.2008.19.8721. Epub 2009 Aug 31.</citation>
    <PMID>19720927</PMID>
  </reference>
  <reference>
    <citation>Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009 Feb 10;27(5):740-5. doi: 10.1200/JCO.2008.16.3055. Epub 2008 Dec 29.</citation>
    <PMID>19114704</PMID>
  </reference>
  <reference>
    <citation>Mainprize T, Lipsman N, Huang Y, Meng Y, Bethune A, Ironside S, Heyn C, Alkins R, Trudeau M, Sahgal A, Perry J, Hynynen K. Blood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility Study. Sci Rep. 2019 Jan 23;9(1):321. doi: 10.1038/s41598-018-36340-0.</citation>
    <PMID>30674905</PMID>
  </reference>
  <reference>
    <citation>Sonabend AM, Stupp R. Overcoming the Blood-Brain Barrier with an Implantable Ultrasound Device. Clin Cancer Res. 2019 Jul 1;25(13):3750-3752. doi: 10.1158/1078-0432.CCR-19-0932. Epub 2019 May 10.</citation>
    <PMID>31076548</PMID>
  </reference>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <last_update_submitted>September 4, 2023</last_update_submitted>
  <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NaviFUS System</keyword>
  <keyword>Blood-Brain Barrier</keyword>
  <keyword>Focused Ultrasound</keyword>
  <keyword>GBM</keyword>
  <keyword>Bevacizumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Glioblastoma</mesh_term>
    <mesh_term>Neoplasms, Nerve Tissue</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
  </intervention_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/NCT04446416
org study id: NF-2019-01
nct id: NCT04446416
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a prospective, single-arm, two stages, open-label, pilot study to investigate the
      efficacy and safety of FUS add-on bevacizumab (BEV) in rGBM patients. The BEV is the best
      physician's choice of standard of care for rGBM after prior radiotherapy and temozolomide
      chemotherapy in the LinKou Chang Gung Memorial Hospital. Eligible patients will be enrolled
      through the process of informed consent.
This trial will be divided into two stages. The study design and procedures will be as
      follows:

      Stage 1:

      Eligible patients will first be administered with BEV 10 mg/kg intravenous (IV) infusion.
      After 30-60 minutes, patients will receive microbubbles (MB) (SonoVue®) 0.1 mL/kg and optimal
      ultrasound exposure doses (based on the acoustic emission feedback FUS power control
      algorithm) generated from the NaviFUS System single exposure unit for up to two minutes every
      2 weeks to transiently open the BBB.

      After 4 weeks of treatment with BEV and single unit FUS-MB treatment, if the patient
      experienced BBB opening using FUS treatment and BEV IV infusion without any serious adverse
      effects (such as brain significant bleeding), then the patient may proceed to stage 2.

      Stage 2:

      Patients who complete stage 1 will enter stage 2 to receive the BEV with MB-mediated multiple
      units of FUS treatment for up to five minutes (but the maximum exposure time per single unit
      is two minutes) every 2 weeks for up to 30 weeks or until evidence of progressive disease,
      unacceptable toxicity, non-compliance with study follow-up, or withdrawal of consent.

      After completion of study treatment, patients will be followed up for 28 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Event
time frame: 38 weeks
description: Number and severity of adverse event
measure: Progression-free survival at 6 months (PFS-6)
time frame: 6 months
description: Estimated rate of patients treated during 6 months without experiencing disease
measure: Tumor shrinkage
time frame: 38 weeks
description: The tumor shrinkage rate (TSR) by measuring the longest diameter and perpendicular diameter of the main mass on MRI scans
measure: Objective response rate (ORR)
time frame: 38 weeks
description: Proportion of subjects in the analysis population who have complete response (CR) or partial response (PR) using Radiologic Assessment in Neuro-Oncology criteria (RANO) criteria
measure: PET uptake
time frame: 38 weeks
description: The uptake of PET (as standard uptake value - SUV and tumor-to-background ratio - TBR) in tumor and in normal contralateral gray matter before start of BEV+FUS treatment will be determined.
measure: Overall survival (OS)
time frame: 38 weeks
description: OS is defined as the time in months from study treatment to death or last follow-up if alive from any cause
measure: Degree of the BBB opening
time frame: 38 weeks
description: The FUS with microbubbles can temporally open the BBB. The spatial permeability of the BBB-opened region will be assessed using dynamic contrast-enhanced MRI (DCE-MRI).
measure: Corticosteroid consumption
time frame: 38 weeks
description: Increase or decrease in corticosteroid use compared to baseline. The mean corticosteroid dosage prior to study treatment will be considered as the patient's baseline.
measure: Quality of life (QoL) assessment with the EORTC QLQ-C30
time frame: 38 weeks
description: The validated European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30) will be used. The EORTC QLQ-C30 is a 30-item questionnaire. All of the response scale to questions are rated on a 4-point Likert scale from 1 = not at all, 2 = a little, 3 = quite a bit, to 4 = very much, and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
measure: Quality of life (QoL) assessment with the EORTC QLQ-BN20
time frame: 38 weeks
description: The EORTC QLQ-BN20 is a QoL assessment specific to brain neoplasms. The questionnaire includes 20 items. All of the response scale to questions are rated on a 4-point Likert scale from 1 = not at all, 2 = a little, 3 = quite a bit, to 4 = very much, and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.
arm group label: Bevacizumab plus NaviFUS System
arm group type: Experimental
description: Device: NaviFUS System BBB Disruption by FUS in recurrent GBM Microbubbles (MB) (SonoVue®) 0.1 mL/kg and optimal ultrasound exposure doses (based on the acoustic emission feedback FUS power control algorithm) generated from the NaviFUS System every 2 weeks to transiently open the BBB.
Drug: Bevacizumab 10 mg/kg every 2 weeks for up to 36 weeks or until evidence of progressive disease, unacceptable toxicity, non-compliance with study follow-up, or withdrawal of consent.
intervention type: Device
intervention name: NaviFUS System
description: Open the BBB using focused ultrasound and contrast agent SonoVue®
arm group label: Bevacizumab plus NaviFUS System
intervention type: Drug
intervention name: Bevacizumab
description: An anti-angiogenic agent to block tumor growth
arm group label: Bevacizumab plus NaviFUS System
other name: Avastin
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Kuo-Chen Wei, M.D.
role: Principal Investigator
affiliation: Chang Gung Memorial Hospital
facility: 
country: Taiwan
citation: Liu HL, Hsu PH, Lin CY, Huang CW, Chai WY, Chu PC, Huang CY, Chen PY, Yang LY, Kuo JS, Wei KC. Focused Ultrasound Enhances Central Nervous System Delivery of Bevacizumab for Malignant Glioma Treatment. Radiology. 2016 Oct;281(1):99-108. doi: 10.1148/radiol.2016152444. Epub 2016 May 18.
PMID: 27192459
citation: Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. doi: 10.1200/JCO.2008.19.8721. Epub 2009 Aug 31.
PMID: 19720927
citation: Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009 Feb 10;27(5):740-5. doi: 10.1200/JCO.2008.16.3055. Epub 2008 Dec 29.
PMID: 19114704
citation: Mainprize T, Lipsman N, Huang Y, Meng Y, Bethune A, Ironside S, Heyn C, Alkins R, Trudeau M, Sahgal A, Perry J, Hynynen K. Blood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility Study. Sci Rep. 2019 Jan 23;9(1):321. doi: 10.1038/s41598-018-36340-0.
PMID: 30674905
citation: Sonabend AM, Stupp R. Overcoming the Blood-Brain Barrier with an Implantable Ultrasound Device. Clin Cancer Res. 2019 Jul 1;25(13):3750-3752. doi: 10.1158/1078-0432.CCR-19-0932. Epub 2019 May 10.
PMID: 31076548
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Glioblastoma
mesh term: Neoplasms, Nerve Tissue
mesh term: Bevacizumab
sharing ipd: No