Children's National Research Institute
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.
Inclusion Criteria: * 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. * Lansky/Karnofsky rating ≥ 60. * Patients must have received at least one line of prior therapy upfront for their disease. * At least four weeks from radiation therapy, prior immunotherapy, or monoclonal antibody therapy. * At least 2 weeks from prior myelosuppressive chemotherapy and post nadir meeting organ function criteria. *…
NeuroNavigation-Guided Focused Ultrasound, every 2 or 4 weeks for 3 cycles of 28 days
Lumason is a sulfur hexafluoride microsphere ultrasound contrast agent which will be used as a mechanical resonator. Lumason will be given in combination with NgFUS every 2 or 4 weeks for 3 cycles of 28 days.
Nivolumab is a monoclonal antibody targeting the immune checkpoint axis PD-1/PD-L1. Nivolumab will be given prior to NgFUS with microbubbles (Lumason) every 2 or 4 weeks for 3 cycles of 28 days.