Actively Recruiting
Study of Low-Intensity Focused Ultrasound in Combination With Immunotherapy in Newly Diagnosed Unmethylated Glioblastoma
Led by University of Virginia · Updated on 2026-05-06
12
Participants Needed
1
Research Sites
140 weeks
Total Duration
On this page
Sponsors
U
University of Virginia
Lead Sponsor
F
Focused Ultrasound Foundation
Collaborating Sponsor
AI-Summary
What this Trial Is About
This is a phase 1 study for patients with newly diagnosed MGMT unmethylated IDH wild-type glioblastoma utilizing autologous activated T-cells armed with bispecific antibody (EGFR-BATs) that recognize the tumor. The investigators hypothesized that the combination of infusions of EGFR BATs and low-intensity focused ultrasound would induce blood-brain barrier opening and increase the permeability of the adoptive immunotherapy. The investigators will radiolabel the EGFR BATs with 89Zr-oxine for subsequent PET imaging to determine the trafficking and uptake of this approach. There is a concern that several infusions of EGFR BATs before BBB opening could change the immune tumor microenvironment that would not allow a permissive BBB after LIFU. Therefore, Arm A will have two LIFU with BBB opening after the 4th and the 8th infusion, and Arm B will have three LIFU with BBB opening after the 1st, 4th, and 8th infusions. This study will determine the safety and feasibility of the combination of low-intensity focused ultrasound (LIFU) with microbubbles BBB opening and EGFR BATs and the access of the adoptive cell immunotherapy to the tumor microenvironment to inform future studies.
CONDITIONS
Official Title
Study of Low-Intensity Focused Ultrasound in Combination With Immunotherapy in Newly Diagnosed Unmethylated Glioblastoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Newly diagnosed supratentorial glioblastoma or gliosarcoma that is IDH wildtype and MGMT unmethylated, expressing EGFR (score ≥ 1 by IHC) confirmed by pathology
- Age between 18 and 70 years
- Karnofsky Performance Status (KPS) of 70 or higher
- Willing and able to provide written informed consent
- Females of childbearing potential and males must agree to use effective contraception
- Maximal surgical tumor removal with residual tumor volume of 2 cm3 or less on immediate post-operative MRI
- Able to communicate during the LIFU BBB opening procedure
- BBB opening targets located in non-eloquent brain areas
- Brain tumor within the treatment area of the NaviFUS system, at least 30 mm from inner skull table
- Negative serum pregnancy test for females of childbearing potential
- Adequate organ function as defined by screening laboratory tests within 10 days before leukapheresis
You will not qualify if you...
- Diagnosis of another malignancy within 2 years, except certain skin cancers and in situ cancers, and no current treatment for other malignancy
- Only biopsy performed; partial resection or greater required
- Tumors located in the cerebellum or brainstem
- Evidence of leptomeningeal dissemination or subependymal spread on initial MRI
- Presence of extracranial metastases
- Evidence of acute intracranial hemorrhage
- Known allergy or hypersensitivity to cetuximab or other EGFR antibodies
- Known sensitivity to gadolinium-based contrast agents
- Known sensitivity to Lumason® ultrasound contrast agent
- Abnormal alpha 1,3 Galactose IgE test indicating likely hypersensitivity to cetuximab
- Claustrophobia
- Non-MRI compatible metallic implants in skull or brain
- Active bleeding or bleeding disorders
- Unable to stop anticoagulant therapy as required
- Scalp atrophy or scars at expected ultrasound transducer location
- Recent myocardial infarction or stroke within one year
- History of angina or depressed left ventricular function (LVEF < 45%) or pacemaker
- Congestive heart failure requiring medical treatment
- HIV infection or active Hepatitis B or C
- Received live vaccine within 30 days before leukapheresis
- Received any treatment for glioblastoma besides surgery
- Pregnant or breastfeeding females
- Ongoing immunosuppressive therapy except corticosteroids
- Any condition or abnormality that may interfere with study participation or results
- Inability to comply with study requirements as judged by investigator
AI-Screening
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Trial Site Locations
Total: 1 location
1
University of Virginia
Charlottesville, Virginia, United States, 22903
Actively Recruiting
Research Team
B
Bettina Wagner, B.A.
CONTACT
C
CJ Woodburn, B.S.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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