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ExAblate Blood-Brain Barrier Disruption for Glioblastoma in Patients Undergoing Standard Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03712293
Recruitment Status : Recruiting
First Posted : October 19, 2018
Last Update Posted : January 9, 2020
Information provided by (Responsible Party):

Tracking Information
First Submitted Date  ICMJE October 16, 2018
First Posted Date  ICMJE October 19, 2018
Last Update Posted Date January 9, 2020
Actual Study Start Date  ICMJE August 28, 2018
Estimated Primary Completion Date October 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2018)
Adverse Events Safety Profile [ Time Frame: 7 months ]
The type and severity of adverse events post-procedure will be assessed for overall safety. Safety of the BBBD procedure will be evaluated through patient examination and MRI assessments during the treatment and by their standard of care follow-up MRI scans and clinical visits. The standard of care follow-up MRI scans will be used to continue safety monitoring post-BBBD procedures and after adjuvant TMZ chemotherapy is completed.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03712293 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2018)
Blood Brain Barrier Opening [ Time Frame: 7 months ]
The ability to open the Blood Brain Barrier with ExAblate Focused Ultrasound will be evaluated by contrast MR imaging. If the procedure was successful, the area treated with show contrast enhancement on MRI.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE ExAblate Blood-Brain Barrier Disruption for Glioblastoma in Patients Undergoing Standard Chemotherapy
Official Title  ICMJE Assessment of Safety and Feasibility of ExAblate Blood-Brain Barrier Disruption for the Treatment of Glioblastoma in Patients Undergoing Standard Chemotherapy
Brief Summary The purpose of this study is to evaluate the safety of the ExAblate Model 4000 Type 2.0 used as a tool to disrupt the BBB in patients with Glioblastoma undergoing standard of care therapy.
Detailed Description This is a prospective, multisingle-center, single-arm study to establish the safety and feasibility of BBB disruption along the periphery of tumor resection cavity using the ExAblate Neuro Model 4000 Type 2.0 (220 kHz) system. For this study, patients will be eligible to enroll in the study prior to beginning the planned adjuvant TMZ chemotherapy phase of treatment. Of note, only patients who are deemed eligible for adjuvant TMZ will be eligible for enrollment. This study will enroll up to 20 subjects.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
This study will enroll up to 10 patients who are eligible and recommended for the standard adjuvant phase of TMZ chemotherapy. The goal is for all subjects to undergo ExAblate Type 2.0 BBB disruption procedures on one of the first three days of each TMZ dosing cycle throughout the adjuvant phase (up to 6 cycles).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma Multiforme
Intervention  ICMJE Device: BBB Disruption with Chemotherapy Arm
The ExAblate BBB disruption of targets associated with enhancing post-resection MRI imaging procedure will be performed with ExAblate 4000 type 2.0 system and will coincide with on one of three first days of each planned TMZ adjuvant therapy cycle as one procedure per cycle.
Study Arms  ICMJE Experimental: BBB Disruption with Chemotherapy Arm
All subjects in this arm will undergo ExAblate Type 2.0 BBBD procedures on one of the first three days of each TMZ dosing cycle throughout the adjuvant phase (up to 6 cycles).
Intervention: Device: BBB Disruption with Chemotherapy Arm
Publications * Park SH, Kim MJ, Jung HH, Chang WS, Choi HS, Rachmilevitch I, Zadicario E, Chang JW. Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy. J Neurosurg. 2020 Jan 3:1-9. doi: 10.3171/2019.10.JNS192206. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 17, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2021
Estimated Primary Completion Date October 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient is eligible for adjuvant TMZ treatment based on the current standard of care.
  2. Men or women.
  3. Age between 19 and 80 years, inclusive.
  4. Able and willing to give informed consent.
  5. Grade IV glioma (GBM) confirmed through assessment of surgical specimens by a board-certified neuropathologist.
  6. Combined radiation/TMZ treatment is completed based on the prescribed standard of care regimen.
  7. Karnofsky rating 70-100 (See Appendix B).
  8. Able to communicate during the ExAblate BBBD procedure.
  9. Able to attend all study visits (i.e., life expectancy of at least 3 months).

Exclusion Criteria:

  1. The sonication pathway to the tumor involves:

    i. More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp.

    ii. Clips or other metallic implanted objects in the skull or the brain, except shunts.

  2. The subject presents with symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, and papilledema).
  3. Patients with cerebellar or brainstem tumors.
  4. Patient receiving bevacizumab (Avastin) therapy.
  5. Patients receiving treatment with corticosteroid doses greater than dexamethasone 16mg daily (or equivalent).
  6. Patients undergoing other concurrent therapies such as chemotherapy wafers, immunotoxins delivered by convection-enhanced delivery, regionally administered gene and viral therapies, immunotherapies, focal irradiation with brachytherapy, stereotactic radiosurgery, laser interstitial thermotherapy, and tumor treatment fields therapy. These regimens have been shown to cause contrast enhancement in the resection cavity boundary, which can be difficult to differentiate from true tumor recurrence [35] [36], [37-39].
  7. Cardiac disease or unstable hemodynamics including:

    i. Documented myocardial infarction within six months of enrollment. ii. Unstable angina on medication. iii. Congestive heart failure. iv. Left ventricular ejection fraction <50%. v. History of a hemodynamically unstable cardiac arrhythmia. vi. Cardiac pacemaker.

  8. Severe hypertension (diastolic BP > 100 on medication).
  9. Anti-coagulant therapy, or medications known to increase risk of hemorrhage within washout period prior to treatment (i.e., antiplatelet or vitamin K inhibitor anticoagulants within 7 days, non-vitamin K inhibitor anticoagulants within 72 hours, or heparin-derived compounds within 48 hours of treatment).
  10. History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage.
  11. Cerebral or systemic vasculopathy.
  12. Evidence of new focal neurological deficits including, but not limited to, motor weakness or speech impairment within 7-14 days prior to the first BBBD procedure.
  13. History of drug or alcohol use disorder.
  14. Active seizure disorder or epilepsy (seizures despite medical treatment).
  15. Known sensitivity to gadolinium-based contrast agents.
  16. Known sensitivity to DEFINITY® ultrasound contrast agent or perflutren.
  17. Contraindications to MRI such as non-MRI-compatible implanted devices.
  18. Large subjects not fitting comfortably into the MRI scanner.
  19. Difficulty lying supine and still for up to 4 hours in the MRI unit or claustrophobia.
  20. Positive pregnancy test (women of childbearing potential).
  21. Severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2 and/or on dialysis.
  22. Right to left or bi-directional cardiac shunt.
  23. Subjects with evidence of cranial or systemic infection.
  24. Subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation, or QT prolongation observed on screening ECG (QTc > 450 for men and >470 for women).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Martin Bernstein +97248131313 ext 628
Contact: Kathy L McDermott +12146302000
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03712293
Other Study ID Numbers  ICMJE BT008K
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party InSightec
Study Sponsor  ICMJE InSightec
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Martin Bernstein InSightec
PRS Account InSightec
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP