Opening the blood-brain barrier for treating brain metastases from lung cancer

A Randomized Pivotal Study Assessing the Safety and Efficacy of Targeted Blood-brain Barrier (BBB) Opening Using Exablate Focused Ultrasound During the Standard of Care Treatment of Brain Metastases of Non-small Cell Lung Cancer (NSCLC) Origin

This study is testing if using focused ultrasound to open the blood-brain barrier can improve treatment for patients with brain metastases from lung cancer who are already receiving standard therapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: InSightec (Industry-sponsored)
• Drugs / interventions: Bevacizumab, chemotherapy, radiation, prednisone, immunotherapy
• Locations: 10 sites (Phoenix, Arizona and 9 other locations)
• Trial ID: NCT05317858 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of using Exablate focused ultrasound to open the blood-brain barrier in patients with brain metastases from non-small cell lung cancer (NSCLC) who are receiving standard immune checkpoint inhibitor therapy. It is a multi-center, randomized, controlled trial that aims to compare the effectiveness of this targeted approach against standard care without the ultrasound intervention. Participants will be monitored for their response to treatment over a six-month period to determine the objective response rate. The study is designed to provide insights into whether this innovative technique can enhance treatment outcomes for patients with brain metastases.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with NSCLC brain metastases who are receiving FDA-approved immune checkpoint inhibitors.

Not a fit: Patients with brain metastases that do not meet the size criteria or those not receiving immune checkpoint inhibitors may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment responses for patients with brain metastases from NSCLC.

How similar studies have performed: Other studies have shown promise in using focused ultrasound techniques for similar applications, indicating potential for success in this novel approach.

Eligibility criteria

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

Where this trial is running

Phoenix, Arizona and 9 other locations

• St. Joseph's Hospital and Medical Center — Phoenix, Arizona, United States (Not_yet_recruiting)
• Miami Cancer Institute at Baptist Health — Miami, Florida, United States (Recruiting)
• Moffitt Cancer Center — Tampa, Florida, United States (Recruiting)
• University of Maryland — Baltimore, Maryland, United States (Recruiting)
• Atrium Health Wake Forest Baptist — Winston-Salem, North Carolina, United States (Recruiting)
• Oregon Health & Science University — Portland, Oregon, United States (Recruiting)
• Rhode Island Hospital — Providence, Rhode Island, United States (Recruiting)
• Johnston Willis Hospital — Richmond, Virginia, United States (Recruiting)
• Sunnybrook Research Institute — Toronto, Ontario, Canada (Completed)
• Samsung Medical Center — Seoul, Seoul, South Korea (Not_yet_recruiting)

Study contacts

• Principal investigator: Manmeet Ahluwalia, MD, MBA — Miami Cancer Institute, Baptist Health South Florida
• Study coordinator: Alyssa Voelker-Christy

Conditions Brain Tumor; Non Small Cell Lung Cancer