NgFUS NIVO: NeuroNavigation-Guided Focused Ultrasound With Nivolumab in Relapsed and Progressive DMG and Other High Grade Brain Tumors

NCT07664176 | Not Yet Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: STUDY00001735
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Diffuse Midline Glioma or Diffuse Intrinsic Pontine Glioma; High Grade Gliomas; Medulloblastoma Recurrent; Ependymoma Recurrent; Atypical Teratoid/Rhabdoid Tumor (ATRT) of the CNS; Brain Tumor Recurrent

Keywords

Focused Ultrasound; Pediatrics; Diffuse Midline Glioma; DMG; Diffuse Intrinsic Pontine Glioma; DIPG; High Grade Glioma; HGG; Nivolumab

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities (DLT) as assessed by CTCAE v6.0.

  Safety will be evaluated by the incidence of DLTs. DLT is defined as toxicities which are at least possibly related to treatment and meeting protocol-specified criteria for grade, duration, severity, and/or delay of subsequent treatment cycles. If the overall toxicity rate exceeds protocol-specified criteria, enrollment will be halted and the study will be amended to modify the treatment plan.

  First treatment through 28 days post-first treatment.

• Percentage of patients completing at least two cycles of planned therapy

  Treatment will be determined feasible if at least 80% of enrolled patients complete at least 2 cycles of planned therapy. Feasibility will be assessed separately for each cohort.

  Enrollment through end of Cycle 2 (each cycle is 28 days).

Secondary Outcomes (3)

• Overall response assessment per RAPNO.

  From screening through 1 year post-final treatment.

• Progression-free survival (PFS)

  From enrollment through up to 2 years post-final treatment.

• Overall survival (OS)

  From enrollment through up to 2 years post-final treatment.

Other Outcomes (6)

• Tissue expression of PD-1 and PD-L1

  From enrollment through immediately after surgery.

• Lymphocyte counts according to FUS area treated

  From enrollment through 3 months post-final treatment.

• Immunologic correlates

  Pre- and post-procedure starting from enrollment through immediately after the final treatment (Cycle 3 Day 0 for Q4Week Group A and Group B, or Cycle 3 Day 14 for Q2Week Group A).

Study Arms (2)

Group A: Patients with relapsed or progressive diffuse midline glioma in the brainstem

EXPERIMENTAL

Patients with relapsed or progressive diffuse midline glioma in the brainstem, receiving nivolumab with NgFUS either every 2 weeks or every 4 weeks.

Device: NeuroNavigation-Guided Focused Ultrasound (NgFUS); Drug: Lumason; Drug: Nivolumab

Group B: Patients with relapsed or progressive high grade brain tumors requiring surgical resection

EXPERIMENTAL

Patients with relapsed or progressive high grade brain tumors that clinically require surgical resection, receiving one dose of NgFUS prior to surgery, and nivolumab with NgFUS every 4 weeks following recovery from surgery.

Device: NeuroNavigation-Guided Focused Ultrasound (NgFUS); Drug: Lumason; Drug: Nivolumab

Interventions

Lumason DRUG

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.

Group A: Patients with relapsed or progressive diffuse midline glioma in the brainstem; Group B: Patients with relapsed or progressive high grade brain tumors requiring surgical resection

Nivolumab DRUG

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.

Group A: Patients with relapsed or progressive diffuse midline glioma in the brainstem; Group B: Patients with relapsed or progressive high grade brain tumors requiring surgical resection

NeuroNavigation-Guided Focused Ultrasound (NgFUS) DEVICE

NeuroNavigation-Guided Focused Ultrasound, every 2 or 4 weeks for 3 cycles of 28 days

Group A: Patients with relapsed or progressive diffuse midline glioma in the brainstem; Group B: Patients with relapsed or progressive high grade brain tumors requiring surgical resection

Eligibility Criteria

• Age: 3 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• At least 1 week or 5 half-lives (whichever is longer) from last targeted therapy.
• If on steroids, stable or decreasing dose for at least 7 days prior to study entry and ≤ 0.4 mg/m2/day of dexamethasone or equivalent.
• Stable or improving neurological status for 7 days prior to study entry.
• Organ function:
• Absolute Neutrophil Count (ANC) ≥750/μL.
• Absolute Lymphocyte Count (ALC) \>500/μL.
• Platelets ≥75K, unsupported.

You may not qualify if:

• 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.
• Tumor presenting with the following imaging characteristics:
• Evidence of uncal herniation.
• Edema and/or mass effect that causes hydrocephalus.
• Significant areas of necrosis within the tumor that the neurosurgeon feels cannot be avoided during the ultrasound sonication.
• Evidence of a significant new hemorrhage. Area of microhemorrhage (defined as less than 5 mm in diameter) in the treatment area can be acceptable but requires the review of the neurosurgeon.
• Containing calcifications in the focused ultrasound sonication beam path and system tools cannot tailor the treatment around these calcification spots.
• Patients who are deemed to have overly bulky tumor by the PI of the study.
• The sonication pathway to the tumor involves:
• More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp.
• Clips, or other non-MRI compatible metallic implanted objects in the skull or the brain, except for shunts.
• Patients receiving anti-coagulant therapy, or medications known to increase risk of hemorrhage, (e.g., ASA, non-steroidal anti-inflammatory drugs \[NSAIDs\], statins). There is no required washout for eligibility assessment, but patients should be off agents for at least 3 days at the time of procedure or until 5 half-lives of the agent, whichever is longer.
• History of a bleeding disorder, coagulopathy or with a history of clinically significant spontaneous tumor hemorrhage.
• Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitis.

Sponsors & Collaborators

• Children's National Research Institute: lead

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Rhabdoid Tumor; Brain Neoplasms; Glioma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Complex and Mixed

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Elizabeth Paronett

CONTACT

202-476-8907; eparonett@childrensnational.org

Julia Batarseh

CONTACT

202-476-5578; jamore@childrensnational.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: June 24, 2026
• Study Start (Estimated): August 24, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share