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

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

NCT ID: NCT05615623

Condition: Brain Tumor

Conditions: Official terms:
Brain Neoplasms
Doxorubicin

Conditions: Keywords:
DIPG
Focused Utrasound
Chemotherapy
Phase I trial
Pediatrics

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Device Feasibility

Masking: None (Open Label)

Intervention:

Intervention type: Device
Intervention name: Exablate
Description: Blood Brain Barrier Disruption (BBBD) via Exablate Type 2 system with microbubble resonators on the day of Doxorubicin infusion to treat DIPG brain tumors
Arm group label: Blood Brain Barrier Disruption (BBBD)

Other name: Exablate BBBD

Intervention type: Drug
Intervention name: Doxorubicin
Description: Doxorubicin infusion
Arm group label: Blood Brain Barrier Disruption (BBBD)

Other name: Adriamycin

Other name: Rubex

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

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.

Criteria for eligibility:
Criteria:
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

Gender: All

Minimum age: 5 Years

Maximum age: 18 Years

Healthy volunteers: No

Locations:

Facility:
Name: Sunnybrook Research Institute

Address:
City: Toronto
Zip: M4N 3M5
Country: Canada

Status: Recruiting

Contact:
Last name: James Rutka, MD

Phone: 416-813-6425
Email: james.rutka@sickkids.ca

Contact backup:
Last name: Maheleth Llinas

Phone: 416-480-6100

Phone ext: 2476
Email: maheleth.llinas@sunnybrook.ca

Investigator:
Last name: Nir Lipsman, MD
Email: Principal Investigator

Investigator:
Last name: James Rutka, MD
Email: Principal Investigator

Start date: January 4, 2023

Completion date: July 4, 2025

Lead sponsor:
Agency: InSightec
Agency class: Industry

Source: InSightec

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05615623