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

Phase 1

Recruiting

• Conditions: Brain Tumor
• Interventions: Device: Exablate; Drug: Doxorubicin

• Registration Number: NCT05630209
• Lead Sponsor: InSightec

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.

Study Timeline

• Study First Submitted: 2022-11-18
• Study First Submitted QC: 2022-11-18
• Study First Posted: 2022-11-29
• Study Start: 2023-01-04
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-01
• Last Update Posted: 2023-11-03
• Primary Completion: 2025-01
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Age between 5 and 21 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
• 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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Blood Brain Barrier Disruption (BBBD)	Exablate	Exablate MR Guided Focused Ultrasound for Blood Brain Barrier Disruption with Doxorubicin for treating pediatric patients with DIPG
Blood Brain Barrier Disruption (BBBD)	Doxorubicin	Exablate MR Guided Focused Ultrasound for Blood Brain Barrier Disruption with Doxorubicin for treating pediatric patients with DIPG

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Nicklaus Children's Hospital; 🇺🇸 Miami, Florida, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States