This is an open-label phase 1 safety and feasibility study evaluating a novel combination therapy for progressive and relapsed diffuse midline glioma (DMG) and other progressive and relapsed high-grade brain tumors. This study combines intravenous nivolumab therapy infused following transient blood-brain barrier opening (BBBO) using low-intensity focused ultrasound with microbubble (LIFU-MB) treatment using NeuroNavigation-Guided Focused Ultrasound (NgFUS).
There are two groups in this study:
* Group A: Patients with relapsed or progressive diffuse midline glioma in the brainstem * Group B: Patients with relapsed or progressive high grade brain tumor that clinically require surgical resection
The primary outcome is to evaluate the safety and feasibility of 3 cycles of nivolumab with BBB disruption using NgFUS with microbubbles in pediatric patients with progressive or relapsed brainstem DMG or with high grade brain tumors after surgery. Secondary outcomes include preliminary efficacy and immunological effects.
Age ≥ 3 and ≤ 25 years.
Diagnosis of brainstem DMG/DIPG or any high-grade brain tumor.
Group A: Relapsed or progressive brainstem DMG.
Group B: Relapsed or progressive high-grade intracranial brain tumor requiring surgical resection.
Symptoms and signs of increased intracranial pressure.
Patients with metallic ventricular peritoneal shunts. Subjects with nonmetallic VP shunts or similar will have a technical evaluation of the screening non-contrast CT scan of the head. During the mapping of the target area, if the technical NaviFUS specialist determines that the patient cannot be treated within the safety limits of the system, the patient will not be eligible and will be considered a screen failure.
Evidence of uncal herniation.
Edema and/or mass effect that causes hydrocephalus.