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

InSightec

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Brain Tumor

Treatments

Device: Exablate

Drug: Doxorubicin

Study type

Interventional

Funder types

Industry

Identifiers

NCT05615623

BT016C

Details and patient eligibility

About

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

Full 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.

Enrollment

3 estimated patients

Sex

All

Ages

5 to 18 years old

Volunteers

No 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