Blood-Brain Barrier Disruption Using Transcranial MRI-Guided Focused Ultrasound

• ClinicalTrials.gov Identifier: NCT02343991
• Recruitment Status: Active, not recruiting
• First Posted: January 22, 2015
• Last Update Posted: January 27, 2020
• Sponsor: InSightec
• Information provided by (Responsible Party): InSightec

Study Description

Brief Summary:

The purpose of this study is to evaluate the safety of BBB disruption using transcranial MRI-guided focused ultrasound in conjunction with an intravenous ultrasound contrast agent to increase the accumulation of doxorubicin in brain tumours and the adjacent brain using the ExAblate Transcranial system (220 kHz). Data will be collected to establish the basic safety of this type of treatment as the basis for later studies to evaluate its clinical efficacy.

Condition or disease	Intervention/treatment	Phase
Brain Tumor	Device: Transcranial ExABlate	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study to Evaluate the Safety and Feasibility of Blood-Brain Barrier Disruption Using Transcranial MRI-Guided Focused Ultrasound With Intravenous Ultrasound Contrast Agents in the Treatment of Brain Tumours With Doxorubicin
• Study Start Date: October 2014
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: July 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Transcranial ExAblate; MR Guided Focused Ultrasound	Device: Transcranial ExABlate; MR Guided Focused Ultrasound; Other Names: ExAblate; TcMRgFUS

Outcome Measures

Primary Outcome Measures :

1. Number of Device and Procedure related adverse events [ Time Frame: At the time of ExAblate transcranial procedure ]
   To evaluate the incidence and severity of adverse events (AEs) associated with the ExAblate transcranial treatment

Secondary Outcome Measures :

1. Severity of Device and Procedure related adverse events [ Time Frame: At the time of ExAblate transcranial procedure ]
   To evaluate the incidence and severity of adverse events (AEs) associated with the ExAblate transcranial treatment

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Men or women.
• Age between 18 and 70 years, inclusive.
• Able and willing to give informed consent.
• Size of the targeted portion of the tumour (i.e. prescribed ROT) is less than 2.5 cm in diameter (16 cm3). The non-targeted tumour tissue may exceed the targeted volume.
• Karnofsky rating 70-100
• ASA score 1-3.
• Able to communicate sensations during the ExAblate MRgFUS procedure.
• Able to attend all study visits (i.e., life expectancy of at least 3 months).
• At least 14 days passed since last brain surgery.

Exclusion Criteria:

• The sonication pathway to the tumour 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)

• Cardiac disease or unstable hemodynamics including:

  i. Documented myocardial infarction within six months of enrolment ii. Unstable angina on medication iii. Congestive heart failure iv. Left ventricular ejection fraction below the lower limit of normal v. History of a hemodynamically unstable cardiac arrythmia vi. Cardiac pacemaker

• Severe hypertension (diastolic BP > 100 on medication)
• Anti-coagulant therapy, or medications known to increase risk of hemorrhage, (e.g.:ASA, non-steroidal anti-inflammatory drugs (NSAIDs), statins)
• History of a bleeding disorder, coagulopathy or with a history of spontaneous tumour hemorrhage
• Abnormal level of platelets (< 100000), PT (>14) or PTT (>36), and INR > 1.3
• Documented cerebral infarction within the past 12 months
• TIA in the last 1 month
• Cerebral or systemic vasculopathy
• Insulin-dependent diabetes mellitus
• Immunosuppression (corticosteroids to prevent/treat brain edema are permitted)
• Known sensitivity to gadolinium-DTPA
• Contraindications to MRI such as non-MRI-compatible implanted devices
• Large subjects not fitting comfortably into the MRI scanner (generally >250 lbs)
• Difficulty lying supine and still for up to 4 hours in the MRI unit or claustrophobia
• Untreated, uncontrolled sleep apnea
• Positive pregnancy test (for pre-menopausal women)
• Known life-threatening systemic disease
• Severely impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2 and/or on dialysis
• Right to left or bi-directional cardiac shunt
• Previous full course of doxorubicin chemotherapy
• Allergy to eggs or egg products

Contacts and Locations

Locations

Canada, Ontario

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada, M4N 3M5

Sponsors and Collaborators

InSightec

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: InSightec
• ClinicalTrials.gov Identifier: NCT02343991
• Other Study ID Numbers: BBB001; 215600 ( Other Identifier: Health Canada )
• First Posted: January 22, 2015
• Last Update Posted: January 27, 2020
• Last Verified: January 2020

Additional relevant MeSH terms:

Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases