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

• Status: Not yet recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: InSightec
• Treatments: Doxorubicin

Criteria

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