Focused Ultrasound BBBD for Glioblastoma
Recruiting in Palo Alto (17 mi)
+16 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: InSightec
No Placebo Group
Approved in 5 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial aims to test the safety and effectiveness of using the Exablate device to temporarily open the blood-brain barrier in patients with suspected Glioblastoma. By doing this, doctors can collect fluid from the brain to check for cancer cells. The study will take place at up to 25 centers in the US.
Do I need to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop all current medications. However, if you are on anti-coagulant or anti-platelet therapy, you must stop these medications within a specific washout period before treatment: antiplatelet or vitamin K inhibitor anticoagulants within 7 days, non-vitamin K inhibitor anticoagulants within 72 hours, or heparin-derived compounds within 48 hours.
What data supports the idea that Focused Ultrasound BBBD for Glioblastoma is an effective treatment?
The available research does not provide specific data on the effectiveness of Focused Ultrasound BBBD for Glioblastoma. However, it does highlight the potential of this treatment in other brain-related conditions. For example, the ExAblate Neuro 4000 system has been used effectively for essential tremor, a condition that causes uncontrollable shaking. This suggests that the technology can precisely target areas in the brain, which could be beneficial for treating glioblastoma. Additionally, the treatment has been shown to help deliver drugs more effectively into brain tumors by temporarily opening the blood-brain barrier, which is a protective shield around the brain. This could potentially make chemotherapy more effective for glioblastoma patients.
12345What safety data exists for focused ultrasound BBBD treatment for glioblastoma?
The ExAblate Neuro 4000 system, used for MR-guided focused ultrasound (MRgFUS), has been evaluated for safety in various studies. It has been used successfully for essential tremor and brain tumor ablation, including glioblastoma, without causing neurological deficits or adverse effects. Preclinical models using the ExAblate 4000 system demonstrated high safety margins with minimal hemorrhage and necrosis. A study specifically on glioblastoma patients undergoing standard chemotherapy found that repeated blood-brain barrier disruptions with MRgFUS were safe and feasible.
13678Is the Exablate Model 4000 treatment promising for glioblastoma?
Yes, the Exablate Model 4000 treatment is promising for glioblastoma. It uses focused ultrasound to temporarily open the blood-brain barrier, allowing chemotherapy drugs to reach the tumor more effectively. This approach has shown potential in increasing the effectiveness of cancer treatments and is considered safe and feasible.
138910Eligibility Criteria
Adults aged 18-80 with suspected glioblastoma brain tumors that can be targeted for surgery or biopsy are eligible. They must have a good performance status (Karnofsky Score >70) and be able to communicate during the procedure. Excluded are those with deep midline or multifocal tumors, certain heart conditions, uncontrolled hypertension, bleeding disorders, severe allergies, active infections including HIV, substance abuse issues, unstable mental health conditions at risk of suicide, and pregnant or breastfeeding women.Inclusion Criteria
I am mostly able to care for myself but may not be able to do active work.
I am between 18 and 80 years old and can consent to treatment.
My brain scans show a tumor that can be targeted with precise radiation.
+2 more
Exclusion Criteria
Abnormal coagulation profile (Platelets < 80,000), PT (>14) or PTT (>36), and INR > 1.3
MR non-compatible metallic implants in the skull or the brain or the presence of unknown MR unsafe devices
Currently in a clinical trial involving an investigational product or non-approved use of a drug or device
+29 more
Participant Groups
The trial is testing the safety and effectiveness of using Focused Ultrasound (Exablate Model 4000) to temporarily disrupt the blood-brain barrier in patients with suspected glioblastoma. This disruption aims to facilitate liquid biopsy—a less invasive method for analyzing tumor tissue.
1Treatment groups
Experimental Treatment
Group I: Exablate BBBDExperimental Treatment1 Intervention
Using Exablate Model 4000 Type 2 for liquid biopsy in subjects with Glioblastoma
Exablate Model 4000 is already approved in United States, European Union, Canada, Japan, China for the following indications:
🇺🇸 Approved in United States as Exablate Model 4000 Type 1.0 System for:
- Essential tremors
- Pain palliation of metastatic bone cancer
- Uterine fibroids
🇪🇺 Approved in European Union as Exablate Neuro for:
- Essential tremors
- Uterine fibroids
🇨🇦 Approved in Canada as Exablate Model 4000 Type 1.0 System for:
- Essential tremors
- Uterine fibroids
🇯🇵 Approved in Japan as Exablate Neuro for:
- Uterine fibroids
🇨🇳 Approved in China as Exablate Model 4000 Type 1.0 System for:
- Uterine fibroids
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
University of North CarolinaChapel Hill, NC
Duke UniversityDurham, NC
Hoag Memorial Hospital PresbyterianNewport Beach, CA
More Trial Locations
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Who Is Running the Clinical Trial?
InSightecLead Sponsor
References
Device profile of exAblate Neuro 4000, the leading system for brain magnetic resonance guided focused ultrasound technology: an overview of its safety and efficacy in the treatment of medically refractory essential tremor. [2021]Introduction: Magnetic Resonance guided Focused UltraSound (MRgFUS) is an emerging technique that utilizes multiple high-energy low-frequency ultrasound beams generated from a multi-element transducer focused onto a single site to cause thermal ablation of the target tissue. The ExAblate Neuro 4000 system is the leading MRgFUS brain system, performing targeted thermal ablation on specific nuclei in the brain. Its precision targeting opens up new and exciting possibilities for future treatments of a wide range of neurological diseases.  Areas covered: This article aims to introduce the non-expert reader (clinician and non-clinicians) to the role of the ExAblate Neuro 4000 System in brain MRgFUS. The current clinical uses of the ExAblate system in the brain are explored with a particular focus on Essential Tremor, where internationally there is most experience, this includes reference to current literature. The safety and efficacy of MRgFUS treatments are explored and the challenges the ExAblate system must overcome to balance these juxtaposed outcomes.Expert opinion: We describe the hopes for future clinical uses of the ExAblate Neuro 4000 system to treat neurological disease and consider further advancements in MRgFUS transducer technology that may open up new exciting frontiers within the brain.
Head phantoms for transcranial focused ultrasound. [2019]In the ongoing endeavor of fine-tuning, the clinical application of transcranial MR-guided focused ultrasound (tcMRgFUS), ex-vivo studies wlkiith whole human skulls are of great use in improving the underlying technology guiding the accurate and precise thermal ablation of clinically relevant targets in the human skull. Described here are the designs, methods for fabrication, and notes on utility of three different ultrasound phantoms to be used for brain focused ultrasound research.
Innovative use of magnetic resonance imaging-guided focused ultrasound surgery for non-invasive breast cancer: a report of two cases. [2020]This report describes the first clinical experience with magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) using the ExAblate 2100 system for non-invasive breast cancer.
Intracranial applications of magnetic resonance-guided focused ultrasound. [2021]The ability to focus acoustic energy through the intact skull on to targets millimeters in size represents an important milestone in the development of neurotherapeutics. Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel, noninvasive method, which--under real-time imaging and thermographic guidance--can be used to generate focal intracranial thermal ablative lesions and disrupt the blood-brain barrier. An established treatment for bone metastases, uterine fibroids, and breast lesions, MRgFUS has now been proposed as an alternative to open neurosurgical procedures for a wide variety of indications. Studies investigating intracranial MRgFUS range from small animal preclinical experiments to large, late-phase randomized trials that span the clinical spectrum from movement disorders, to vascular, oncologic, and psychiatric applications. We review the principles of MRgFUS and its use for brain-based disorders, and outline future directions for this promising technology.
Focused Ultrasound Strategies for Brain Tumor Therapy. [2022]A key challenge in the medical treatment of brain tumors is the limited penetration of most chemotherapeutic agents across the blood-brain barrier (BBB) into the tumor and the infiltrative margin around the tumor. Magnetic resonance-guided focused ultrasound (MRgFUS) is a promising tool to enhance the delivery of chemotherapeutic agents into brain tumors.
First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound. [2020]Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation of target tissues. While this emerging modality is increasingly used for the treatment of various types of extracranial soft tissue tumors, it has only recently been acknowledged as a modality for noninvasive neurosurgery. MRgFUS has been particularly successful for functional neurosurgery, whereas its clinical application for tumor neurosurgery has been delayed for various technical and procedural reasons. Here, we report the case of a 63-year-old patient presenting with a centrally located recurrent glioblastoma who was included in our ongoing clinical phase I study aimed at evaluating the feasibility and safety of transcranial MRgFUS for brain tumor ablation. Applying 25 high-power sonications under MR imaging guidance, partial tumor ablation could be achieved without provoking neurological deficits or other adverse effects in the patient. This proves, for the first time, the feasibility of using transcranial MR-guided focused ultrasound to safely ablate substantial volumes of brain tumor tissue.
Sonoablation and application of MRI guided focused ultrasound in a preclinical model. [2014]Stereotaxic sonoablative surgery by MRI guided high intensity focused ultrasound (FUS) holds great potential in disorders of the central nervous system (CNS). We previously described the ExAblate 2000 system (InSightec, Tirat Carmel, Israel), currently in use for various pathologies including uterine, liver, and, breast tumors, and referred to as the "body" system. Using a porcine model we have previously demonstrated, using the body system, the ablative capacity and thermal transfer in the cortex; developed a reproducible and translational model of craniectomy and post-operative recovery in FUS; and determined a grouping strategy based on thermal ablation and pathologic incremental changes in the cortex. Here we describe a novel ExAblate 4000 system that is designed specifically to treat CNS disorders ("head" system). Twenty-two swine underwent an improved wide craniectomy for positioning of the ExAblate 4000 containing 1024 elements arrayed with MRI guidance. Further neurologic and pathological analysis was performed 1 week post-operatively. Subjects underwent a wide craniectomy followed by high intensity MR guided focused ultrasound (MRgHIFU) sonoablation. Thermal ultrasonic ablative lesions were achieved in all subjects (n=22) ranging from 52-65°C following ∼70 consecutive sonications at 80 watts. These subjects were grouped based on thermal ablative lesions and post-operative staging (MRI, gross and microscopic pathology). Our results indicate the reproducibility of a porcine model for cerebral ablation, achieved across a dynamic temperature range, and well tolerated in this cohort. The ExAblate 4000 system is efficient through a wide craniectomy as well as a closed skull and demonstrates a high safety margin. Incremental hemorrhage and necrosis were minimal and energy dependent, indicating MRgHIFU can be used for the treatment of various cerebral pathologies and movement disorders.
Safety and feasibility of multiple blood-brain barrier disruptions for the treatment of glioblastoma in patients undergoing standard adjuvant chemotherapy. [2023]Glioblastoma (GBM) remains fatal due to the blood-brain barrier (BBB), which interferes with the delivery of chemotherapeutic agents. The purpose of this study was to evaluate the safety and feasibility of repeated disruption of the BBB (BBBD) with MR-guided focused ultrasound (MRgFUS) in patients with GBM during standard adjuvant temozolomide (TMZ) chemotherapy.
Past, present and future of Focused Ultrasound as an adjunct or complement to DIPG/DMG therapy: A consensus of the 2021 FUSF DIPG meeting. [2023]Diffuse Intrinsic Pontine Glioma (DIPG), now known as Diffuse Midline Glioma (DMG) is a devastating pediatric brain tumor with limited treatment options and a very poor prognosis. Despite more than 250 clinical trials aimed to treat children diagnosed with DMG, no curative therapies currently exist for this patient population. A major obstacle has been the intact blood brain barrier (BBB) which prevents most therapeutics from crossing into the tumor bed. Focused Ultrasound (FUS) is an emerging, noninvasive medical technology which has been shown in both preclinical and clinical research to disrupt the blood brain barrier safely and temporarily. FUS blood brain barrier opening has been studied in combination with chemotherapies in preclinical DMG models, and this technology is now being investigated in clinical trials for the treatment of pediatric brain tumors. Focused ultrasound has additional mechanisms of action, including sonodynamic therapy and radiation sensitization, that hold promise as future DMG therapies as well. This paper, largely based off the proceedings from a workshop held by the Focused Ultrasound Foundation in October of 2021, summarizes the current state of the field of focused ultrasound for DIPG/DMG, including preclinical, technical, and clinical summaries in addition to recommended next steps for continued advancement of the game changing technology of Focused Ultrasound.
Ultrasound-Induced Blood-Brain-Barrier Opening Enhances Anticancer Efficacy in the Treatment of Glioblastoma: Current Status and Future Prospects. [2020]Glioblastoma multiforme (GBM) diffusely infiltrates normal brain tissue. The presence of the blood-brain barrier (BBB) poses difficulties for targeted delivery of currently available antitumor drugs. Novel brain drug delivery strategies are far from satisfactory for glioma treatment. Recently, focused ultrasound (FUS) combined with microbubbles presents a transient, reversible, and noninvasive approach for local induction of BBB opening. This strategy demonstrated its potential to increase local concentrations of both diagnostic and therapeutic agents in glioma therapy. Current status and related physic mechanisms of this drug delivery technique are discussed in this review. Delivery efficiency enhancement in many preclinical glioma models was obtained by FUS-BBB opening combined with various nanoparticles. And, the clinical translational status of FUS-BBB will be discussed.