Blood Brain Barrier (BBB) Disruption Using Exablate Focused Ultrasound With Doxorubicin for Treatment of Pediatric DIPG

NCT ID: NCT05615623

Last Updated: 2025-04-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-04
• Study Completion Date: 2026-07-31

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier disruption with Exablate Model 4000 Type 2.0/2.1 in combination with Doxorubicin therapy for the treatment of DIPG in pediatric patients

Detailed Description

This is a prospective, single arm, non-randomized feasibility study to evaluate the safety, feasibility and preliminary efficacy of Blood Brain Barrier Disruption (BBBD) using the Exablate Type 2 system in pediatric patients with Diffuse Intrinsic Pontine Gliomas (DIPG) undergoing Doxorubicin chemotherapy. The study will be conducted at a single center in Canada. Patients will undergo 3 treatment cycles, approximately 4 -6 weeks apart. The study aims to establish feasibility and safety of Exablate BBBD in conjunction with Doxorubicin in the treatment of pediatric DIPG and assess preliminary efficacy in this patient population.

Conditions

Brain Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DEVICE_FEASIBILITY
• Blinding Strategy: NONE

Study Groups

Blood Brain Barrier Disruption (BBBD)

Exablate MR Guided Focused Ultrasound for Blood Brain Barrier Disruption with Doxorubicin for treating pediatric patients with DIPG

Group Type: EXPERIMENTAL

Exablate

Intervention Type: DEVICE

Blood Brain Barrier Disruption (BBBD) via Exablate Type 2 system with microbubble resonators on the day of Doxorubicin infusion to treat DIPG brain tumors

Doxorubicin

Intervention Type: DRUG

Doxorubicin infusion

Interventions

Exablate

Blood Brain Barrier Disruption (BBBD) via Exablate Type 2 system with microbubble resonators on the day of Doxorubicin infusion to treat DIPG brain tumors

Intervention Type: DEVICE

Doxorubicin

Doxorubicin infusion

Intervention Type: DRUG

Other Intervention Names

Exablate BBBD; Adriamycin; Rubex

Eligibility Criteria

Inclusion Criteria

• Age between 5 and 18 years, inclusive
• Patient diagnosed with DIPG
• At least 4-week and not greater than 12 weeks from completion of radiation therapy
• Post-radiation imaging does not show evidence of necrosis/ hemorrhage or other features that contraindicate MRgFUS
• Able to attend all study visits and with life expectancy of at least 6 months
• Able and willing to give consent and/or assent or have a legal guardian who is able and willing to do so
• If on steroids, stable or decreasing dose for at least 7 days prior to study entry
• If brain surgery occurred, at least 14 days passed since last brain surgery and the patient is fully recovered and neurologically stable

Exclusion Criteria

• Evidence of cranial or systemic infection
• Known life-threatening systemic disease
• Previous treatment with complete cumulative doses of Doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones
• Contraindication to Doxorubicin. - Known sensitivity to DEFINITY® ultrasound contrast agent or known hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol. - Known sensitivity to gadolinium-based contrast agents
• Active seizure disorder or epilepsy (seizures despite medical treatment) for a minimum of 4 weeks prior to first cycle/Exablate BBBD procedure captured by history
• Patients with positive HIV status. - Immunosuppression (corticosteroids to prevent/treat brain edema are permitted)
• Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitis
• Hypertension per age
• History of a bleeding disorder, coagulopathy or with a history of spontaneous tumour hemorrhage
• Anti-coagulant therapy, or medications known to increase risk of hemorrhage, (e.g., ASA, non-steroidal anti-inflammatory drugs [NSAIDs], statins) within washout period prior to treatment
• Patient receiving bevacizumab (Avastin) therapy or increasing doses of steroids
• Symptoms and signs of increased intracranial pressure
• Previous participation in other chemotherapy, molecularly targeted therapy or immunotherapy treatment-related phase 1 or 2 trials
• Tumor not visible on any pre-therapy or post-radiation imaging

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

InSightec

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Sunnybrook Research Institute

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Nadir Alikacem

Role: CONTACT

nadira@insightec.com

+12146302000

Facility Contacts

James Rutka, MD

Role: primary

james.rutka@sickkids.ca

416-813-6425

Maheleth Llinas

Role: backup

maheleth.llinas@sunnybrook.ca

416-480-6100 ext. 2476

Other Identifiers

BT016C

Identifier Type: -

Identifier Source: org_study_id