Blood-brain Barrier (BBB) Opening Using Exablate Focused Ultrasound With Standard of Care Treatment of NSCLC Brain Mets

NCT ID: NCT05317858

Last Updated: 2025-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-12

Study Completion Date

2027-12-01

Brief Summary

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The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier opening with Exablate Model 4000 Type 2.0/2.1 for the treatment of NSCLC brain metastases in patients who are undergoing planned FDA approved, on-label systemic therapy utilizing immune checkpoint inhibitors.

Detailed Description

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This is a prospective, multi-center, randomized, two-arm, controlled, pivotal clinical trial to evaluate the safety and efficacy of targeted blood brain barrier opening using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned FDA approved, on-label systemic therapy utilizing immune checkpoint inhibitors for their primary disease. The study will be conducted at up to 30 centers in the US. The immunotherapy regimen (every 3 weeks for 6 cycles) of prescribed ICI therapy is per the FDA approved labeling and the subjects prescribed standard of care therapy for their primary NSCLC. The study aims to demonstrate superiority of Exablate BBBO targeted to their brain metastases over the standard of care without Exablate BBBO with respect to the percentage of subjects achieving Objective Response Rate (ORR) by 6 months follow-up.

Conditions

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Brain Tumor Non Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Imaging Core Lab is Blinded

Study Groups

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ICI Systemic Therapy with Exablate BBBO

Using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned ICI Systemic Therapy.

Group Type EXPERIMENTAL

Blood Brain Barrier Opening - Oncology

Intervention Type DEVICE

BBB opening via Exablate Type 2 system with microbubble resonators on the day of ICI infusion to treat brain metastases.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab infusion

Atezolizumab

Intervention Type DRUG

Atezolizumab infusion

Cemiplimab

Intervention Type DRUG

Cemiplimab infusion

Nivolumab

Intervention Type DRUG

Nivolumab infusion

Iptilimumab

Intervention Type DRUG

Iptilimumab infusion

Control Arm (ICI Systemic Therapy on-label use only)

subjects will undergo planned on-label ICI Systemic Therapy.

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type DRUG

Pembrolizumab infusion

Atezolizumab

Intervention Type DRUG

Atezolizumab infusion

Cemiplimab

Intervention Type DRUG

Cemiplimab infusion

Nivolumab

Intervention Type DRUG

Nivolumab infusion

Iptilimumab

Intervention Type DRUG

Iptilimumab infusion

Interventions

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Blood Brain Barrier Opening - Oncology

BBB opening via Exablate Type 2 system with microbubble resonators on the day of ICI infusion to treat brain metastases.

Intervention Type DEVICE

Pembrolizumab

Pembrolizumab infusion

Intervention Type DRUG

Atezolizumab

Atezolizumab infusion

Intervention Type DRUG

Cemiplimab

Cemiplimab infusion

Intervention Type DRUG

Nivolumab

Nivolumab infusion

Intervention Type DRUG

Iptilimumab

Iptilimumab infusion

Intervention Type DRUG

Other Intervention Names

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Exablate BBBO KEYTRUDA Tecentriq LIBTAYO

Eligibility Criteria

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Inclusion Criteria

* Participant is ≥ 18 years of age
* The participant provides written informed consent for the trial
* Participant is willing to comply with all study procedures for the duration of the study
* Participant has a Karnofsky Performance Status ≥ 70% and/or ECOG 0-2
* Participant is a NSCLC subject prescribed immune checkpoint inhibitor systemic therapy according to on-label use with the target brain lesion(s) measuring ≥ 0.5 cm in longest diameter. Target mets may include: De novo mets for which surgery and radiation can be deferred, Mets with or without history of prior radiation, Mets with history of radiation after at least 8 weeks since last radiation treatment, and In the event a previously treated met has progressed according to institutional practice within 4 weeks post radiation treatment, the met may be study eligible, and/or if in the opinion of the Investigator, the subject may benefit from the study procedure.
* Female subject is not planning pregnancy during the study duration and confirmed NOT PREGNANT each procedure day.
* Screening/Baseline laboratory values Screening/Baseline should adhere to local standard of care lab values for ICI therapy

Exclusion Criteria

* Participant has evidence of acute intracranial hemorrhage
* Participant at risk for spontaneous intracranial hemorrhage (e.g., history of metastatic melanoma or other tissue histology).
* Participant has signs and symptoms of increased intracranial pressure or symptomatic mass effect, midline shift or evidence of subfalcine, uncal or tonsillar herniation.
* Participant receiving Bevacizumab (Avastin) therapy, or other drugs with a proclivity for causing bleeding.
* History of bleeding disorders or tissue pathologies which increase the subject's risk of hemorrhage for anticoagulation medications, implement pre-surgical standard procedure to avoid increased risk of a bleeding event.
* Participant has an infectious viral infection such as active Hepatitis B, Hepatitis C or detectable HIV viral load or participants with active bacterial infection such as TB (Bacillus tuberculosis) that may, in the opinion of the investigator, interfere with the subject receiving the study therapy or procedures or otherwise impact their participation in the trial.
* Subjects with evidence of cranial or systemic infection.
* Participant has received a solid organ or hematopoietic stem cell transplant.
* Participant has received a live vaccine within 28 days prior to the first on-study ICI infusion with or without Exablate.
* Known sensitivity to DEFINITY® ultrasound contrast agent or hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol, as found in MiraLAX and bowel prep products.
* Contraindications to MRI and gadolinium-DTPA including non-MRI-compatible implanted devices, severe claustrophobia, unable to lie supine in MRI.
* Subjects with significant liver dysfunction, (cirrhosis, hemochromatosis, severe alcohol abuse, or active hepatitis (autoimmune or infectious))
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first on-study ICI infusion with or without Exablate. Note: prophylactic steroid use for ICI and chemotherapy infusion per institutional practice is allowed per protocol.
* Has a known additional malignancy that requires active treatment that would interfere with study procedures.
* Known presence of leptomeningeal disease.
* Has a diagnosis of active autoimmune disease (e.g., autoimmune Hepatitis, Guillain-Barre Syndrome, etc.) requiring systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. History of (non-infectious) pneumonitis that requires steroids or has current pneumonitis
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
* Subject is currently enrolled in another intervention based clinical trial
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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InSightec

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Manmeet Ahluwalia, MD, MBA

Role: PRINCIPAL_INVESTIGATOR

Miami Cancer Institute, Baptist Health South Florida

Locations

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St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Site Status NOT_YET_RECRUITING

Miami Cancer Institute at Baptist Health

Miami, Florida, United States

Site Status RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

University of Maryland

Baltimore, Maryland, United States

Site Status RECRUITING

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status RECRUITING

Johnston Willis Hospital

Richmond, Virginia, United States

Site Status RECRUITING

Sunnybrook Research Institute

Toronto, Ontario, Canada

Site Status COMPLETED

Samsung Medical Center

Seoul, Seoul, South Korea

Site Status COMPLETED

Countries

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United States Canada South Korea

Central Contacts

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Alyssa Voelker-Christy

Role: CONTACT

817-948-5219

Facility Contacts

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Jamie Sanders

Role: primary

602-406-8605

Daylan L Santana, RN

Role: primary

7865278528

Juliana Montoya

Role: backup

786-527-8864

Sebastian Matzza

Role: primary

813-745-1158

Carie Bliss

Role: backup

(813) 745-2131

Kaitlyn Henry

Role: primary

410-328-0939

Rayne Noyes

Role: backup

410-328-5332

Maria Duffy

Role: primary

(401) 444-2243

Owen Leary

Role: backup

(401) 606-8388

Kanwalcharan S Sahni, MD

Role: primary

804-330-4990

Other Identifiers

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BT012

Identifier Type: -

Identifier Source: org_study_id

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