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

NCT03712293 | Completed DMC

• 1 other identifier: BT008K
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (1)

• Adverse Events Safety Profile

  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.

  7 months

Secondary Outcomes (1)

• Blood Brain Barrier Opening

  7 months

Study Arms (1)

BBB Disruption with Chemotherapy Arm

EXPERIMENTAL

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).

Device: BBB Disruption with Chemotherapy Arm

Interventions

BBB Disruption with Chemotherapy Arm DEVICE

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.

BBB Disruption with Chemotherapy Arm

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• The subject presents with symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, and papilledema).
• Patients with cerebellar or brainstem tumors.
• Patient receiving bevacizumab (Avastin) therapy.
• Patients receiving treatment with corticosteroid doses greater than dexamethasone 16mg daily (or equivalent).
• 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 \[35\] \[36\], \[37-39\].
• 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.
• Severe hypertension (diastolic BP \> 100 on medication).
• 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).
• History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage.
• Cerebral or systemic vasculopathy.
• 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.

Sponsors & Collaborators

• InSightec: lead

Study Sites (1)

Severance Hospital, Yonsei University Health System

Seoul, Seodaemun-gu, 03722, South Korea

Location

Related Publications (2)

• Park SH, Kim MJ, Jung HH, Chang WS, Choi HS, Rachmilevitch I, Zadicario E, Chang JW. One-Year Outcome of Multiple Blood-Brain Barrier Disruptions With Temozolomide for the Treatment of Glioblastoma. Front Oncol. 2020 Sep 10;10:1663. doi: 10.3389/fonc.2020.01663. eCollection 2020.

  PMID: 33014832 DERIVED

• 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;134(2):475-483. doi: 10.3171/2019.10.JNS192206. Print 2021 Feb 1.

  PMID: 31899873 DERIVED

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Martin Bernstein

  InSightec

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: October 16, 2018
• First Posted: October 19, 2018
• Study Start: August 28, 2018
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: March 5, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)