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

Sponsor

InSightec (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05615623

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Brain Tumor	Device: Exablate Drug: Doxorubicin	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

3 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Device Feasibility

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)

Actual Study Start Date :

Jan 4, 2023

Anticipated Primary Completion Date :

Jan 4, 2025

Anticipated Study Completion Date :

Jul 4, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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

Other Outcome Measures

Tumor Volume [Immediately post BBBD sonication]
Average volume of contrast-enhancement on post sonicated MRI scans will be compared with pre-sonicated scans
Progression Free Survival (PFS) and Overall Survival (OS) [2 years]
PFS will be assessed based on the Response Assessment in Pediatric Neuro-Oncology (RAPNO) scale. Tumor related biomarkers will be compared before and after the BBBD procedure

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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