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

NCT ID: NCT05630209

Last Updated: 2025-10-02

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: 2026-06-30

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier disruption with Exablate Model 4000 Type2.0/2.1 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 up to three sites in the United States. 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 21 years, inclusive. Subjects younger than 5 years old may be eligible after discussion with the Sponsor Medical Monitor/designee (i.e. DSMB).
• 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
• If brain surgery occurred, at least 14 days passed since last brain surgery and the patient is fully recovered and neurologically stable
• If on steroids, stable or decreasing dose for at least 7 days prior to study entry
• Stable or improving neurologic status for 7 days prior to study entry
• Able and willing to give consent and/or assent or have a legal guardian who is able and willing to do so
• Able to attend all study visits and with life expectancy of at least 6 months

Exclusion Criteria

• Tumor not visible on any pre-therapy or post-radiation imaging
• Previous participation in other chemotherapy, molecularly targeted therapy, or immunotherapy treatment-related phase 1 or 2 trials
• Symptoms and signs of increased intracranial pressure
• Subject with metastatic disease
• Subject with ventricular peritoneal shunt
• Subject receiving bevacizumab (Avastin) therapy or increasing doses of steroids
• 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
• History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage.
• Hypertension per age
• Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitis
• Immunosuppression (corticosteroids to prevent/treat brain edema are permitted).
• Patients with positive HIV status
• 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
• Known sensitivity to gadolinium-based contrast agents
• Known sensitivity to DEFINITY® ultrasound contrast agent or known hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol
• Contraindication to Doxorubicin
• Previous treatment with complete cumulative doses of Doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones
• Severely impaired renal function with estimated glomerular filtration rate <2 standard deviations for age
• Patients that may require trastuzumab during the study
• Patients that may require inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp during the study

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

InSightec

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status: RECRUITING

Nicklaus Children's Hospital

Miami, Florida, United States

Site Status: RECRUITING

Cook Children's Health Care System

Fort Worth, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Nadir Alikacem

Role: CONTACT

nadira@insightec.com

+12146302000

Facility Contacts

Elizabeth Paronett

Role: primary

eparonett@childrensnational.org

202-476-5551

Toba Niazi, MD

Role: primary

Toba.niazi@nicklaushealth.org

3056628386

Ana Diaz, ARNP

Role: backup

DIPG.ClinicalTrial@nicklaushealth.org

Rachel Collins, MSN, RN, CPN, CCRC

Role: primary

FocusedUltrasound@cookchildrens.org

682-885-1904

Other Identifiers

BT016

Identifier Type: -

Identifier Source: org_study_id