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

Brain Tumor Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05630209
• Other study ID #: BT016
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 4, 2023
• Est. completion date: January 2026

Study information

• Verified date: November 2023
• Source: InSightec
• Contact: Nadir Alikacem
• Phone: +12146302000
• Email: nadira[@]insightec.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: January 2026
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 21 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumor

Intervention

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

Drug:
• Doxorubicin
Doxorubicin infusion

Locations

Country	Name	City	State
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
InSightec

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progression Free Survival (PFS)	PFS will be assessed based on the Response Assessment in Pediatric Neuro-Oncology (RAPNO) scale.	2 years
Primary	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	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