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

A Safety and Feasibility Study to Evaluate Blood Brain Barrier Disruption Using Exablate MR Guided Focused Ultrasound in Combination With Doxorubicin in Treating Pediatric Patients With Diffuse Intrinsic Pontine Gliomas (DIPG)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Brain Tumor
• Intervention / Treatment: Device: Exablate; Drug: Doxorubicin

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Health Care System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blood Brain Barrier Disruption (BBBD); Exablate MR Guided Focused Ultrasound for Blood Brain Barrier Disruption with Doxorubicin for treating pediatric patients with DIPG	Device: 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; Other Names: Exablate BBBD; Drug: Doxorubicin; Doxorubicin infusion; Other Names: Adriamycin; Rubex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	All adverse events from first treatment to end of study will be documented and reported according to the CTCAE terminology and severity scale	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Brain Barrier Disruption (BBBD)	BBBD will be assessed as a comparative ratio measured in pre and post-sonication contrast-enhanced MR images	immediately post BBBD sonication

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS will be assessed based on the Response Assessment in Pediatric Neuro-Oncology (RAPNO) scale.	2 years

Collaborators and Investigators

• Sponsor: InSightec

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: November 18, 2022
• First Submitted That Met QC Criteria: November 18, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pediatrics; Chemotherapy; DIPG; Focused Ultrasound; Phase I trial
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Doxorubicin
• Other Study ID Numbers: BT016

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No