Sonobiopsy for Glioblastoma

Overseen By Albert Kim, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Disqualifiers: Previous cancer, Coagulopathy, Skull defect, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical study to evaluate sonobiopsy is significant because sonobiopsy will fundamentally enhance the clinician's insight into the molecular features of an intracranial lesion to tailor treatment approaches and optimize outcomes. In addition to the standard diagnostics of anatomic imaging and surgical histology, sonobiopsy has the potential to become the third pillar for brain tumor management by radically advancing the ability to easily and regularly acquire tumor genetic and molecular signatures. This enhanced capability will have a dramatic impact on patient survival and quality of life.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Sonobiopsy for Glioblastoma?

Research shows that Sonobiopsy, which uses focused ultrasound and microbubbles, can safely increase the levels of tumor markers in the blood, helping in the noninvasive diagnosis of brain diseases. Additionally, similar techniques have been shown to temporarily open the blood-brain barrier, allowing better delivery of treatments to brain tumors. ^{1 2 3 4 5}

Is sonobiopsy safe for humans?

Research shows that sonobiopsy, which uses focused ultrasound and microbubbles, has been tested in humans with glioblastoma and high-grade glioma. The studies found it to be safe, with no significant harmful effects observed during the trials. ^{1 2 4 6 7}

How is the sonobiopsy treatment for glioblastoma different from other treatments?

Sonobiopsy is unique because it uses focused ultrasound and microbubbles to noninvasively collect tumor biomarkers from the blood, helping diagnose brain diseases without surgery. This approach is different from traditional methods as it enhances the detection of tumor-specific DNA in the bloodstream, providing a safer and less invasive diagnostic option. ^{1 2 3 5 8}

Research Team

Albert Kim, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults with a new diagnosis of glioblastoma, where the tumor is larger than 3 cm and close to the brain's surface. Candidates must be planning surgery to remove the tumor and have not had previous cancer treatments or cranial surgeries. People with MRI contraindications, skin diseases affecting ultrasound use, coagulopathy, metal in their head, or unstable heart/lung conditions cannot join.

Inclusion Criteria

I am 18 years old or older.

I am scheduled for surgery to remove my tumor.

I have a recurring brain tumor confirmed by a recent MRI and am planning surgery.

Exclusion Criteria

Ferrous material in the scalp or skull

Known hypersensitivity to polyethylene glycol

I do not have any recent serious heart or lung problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Sonobiopsy Procedure

Participants undergo the sonobiopsy procedure, which involves using a customized ultrasound probe and standard ultrasound contrast agent, followed by planned tumor removal surgery.

1 day

1 visit (in-person)

Post-Procedure Monitoring

Blood and possibly skin samples are collected for genetic analysis to compare against tumor mutations. An additional MRI scan is performed to assess imaging changes.

1-2 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the sonobiopsy procedure.

4 weeks

Treatment Details

Interventions

• Sonobiopsy

Trial Overview The study tests sonobiopsy—a noninvasive method that could help doctors understand brain tumors better by regularly collecting genetic and molecular information without surgery. This could lead to personalized treatment plans aimed at improving survival and life quality.

Participant Groups

Group I: Sonobiopsy Experimental Treatment 4 Interventions

* Once enrolled, participants would be prepared for standard of care surgery. * The sonobiopsy involves the standard procedure for a biopsy, but the biopsy needle is replaced with a customized ultrasound probe, a standard ultrasound contrast agent (microbubbles) is injected intravenously, and the probe is turned on for 3 minutes for the sonobiopsy. Then the planned surgery to remove the tumor will occur. * An additional brief MRI scan will be obtained using the intraoperative MRI to define imaging changes (if any) that occur as a result of the sonobiopsy procedure. The imaging protocols will include a 3D T2-weighted (T2w) scan, and 3D contrast T1-weighted (T1w) with dynamic contrast enhancement and if time allows T2\* sequence. * Blood will be collected at several time points. * A small skin biopsy or another blood draw will be drawn for comparison against the genetic mutations shown in the tumor. * The blood, tumor, and skin (if applicable) will undergo genetic analysis.

Sonobiopsy is already approved in United States for the following indications:

Approved in United States as Sonobiopsy for:

• Glioblastoma
• Brain Tumors

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The first-in-human trial of sonobiopsy in glioblastoma patients demonstrated its feasibility and safety, successfully enhancing circulating tumor biomarker levels in blood samples after focused ultrasound treatment.

Histological analysis confirmed the procedure's safety, showing minimal inflammatory response and modulation of specific genes related to cell structure, supporting further research into sonobiopsy for noninvasive brain disease diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human prospective trial of sonobiopsy in glioblastoma patients using neuronavigation-guided focused ultrasound. Yuan, J., Xu, L., Chien, CY., et al.[2023]

The first-in-human trial of sonobiopsy in high-grade glioma patients demonstrated its feasibility and safety, successfully enriching plasma circulating tumor DNA (ctDNA) after focused ultrasound treatment.

Sonobiopsy significantly increased levels of specific tumor biomarkers in the blood, including a 5.6-fold increase in TERT mutation ctDNA, indicating its potential for noninvasive molecular diagnosis of brain diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human prospective trial of sonobiopsy in high-grade glioma patients using neuronavigation-guided focused ultrasound. Yuan, J., Xu, L., Chien, CY., et al.[2023]

Ultrastable lipid-coated microbubbles serve as an effective ultrasonic contrast agent for brain imaging, enhancing the visibility of gliomas for up to 1 hour after intravenous administration.

These microbubbles allow for earlier detection of brain tumors, visualizing lesions 40% sooner than traditional methods, and improve the signal-to-noise ratio during ultrasound scans, indicating their potential for better diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative assessment of tumor enhancement by ultrastable lipid-coated microbubbles as a sonographic contrast agent. Simon, RH., Ho, SY., Perkins, CR., et al.[2019]

In a phase I study involving 5 patients with high-grade glioma, MR-guided focused ultrasound (MRgFUS) was successfully used to temporarily open the blood-brain barrier (BBB) without surgery, allowing for enhanced delivery of chemotherapy.

The procedure was safe and well-tolerated, showing no adverse effects, and resulted in a significant increase in chemotherapy delivery to the targeted brain tissue, indicating its potential for improving treatment efficacy in brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility Study. Mainprize, T., Lipsman, N., Huang, Y., et al.[2020]

Using MRI-guided focused ultrasound (FUS) combined with microbubbles can effectively open the blood-brain barrier (BBB) and blood-tumor barrier (BTB), enhancing the delivery of brain-penetrating nanoparticle (BPN) gene therapies to brain tumors.

After FUS treatment, the flow of therapeutic agents through tumor tissue increased significantly, with interstitial flow velocity doubling and dispersion of BPNs improving by over 100%, indicating a promising method for improving gene therapy efficacy in brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection. Curley, CT., Mead, BP., Negron, K., et al.[2023]

Transcranial microbubble-enhanced focused ultrasound (MB-FUS) safely and effectively opens the blood-brain barrier (BBB) in patients with infiltrating gliomas, as demonstrated in a Phase 0 clinical trial with MRI and histopathology confirming reproducible results.

The study found a significant increase in drug accumulation in treated tumor tissues, with a 2.2-fold increase in fluorescein compared to untreated areas, suggesting that MB-FUS could enhance the delivery of therapeutics for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Localized blood-brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions-controlled focused ultrasound. Anastasiadis, P., Gandhi, D., Guo, Y., et al.[2022]

Focused ultrasonography can effectively disrupt the blood-brain barrier, which is a major challenge in delivering chemotherapy to glioblastoma tumors, potentially enhancing the efficacy of treatment.

The review discusses both preclinical and clinical studies that support the use of focused ultrasonography to improve the delivery of oncotherapeutic agents, suggesting a promising future for this technique in glioblastoma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasonography-Mediated Blood-Brain Barrier Disruption in the Enhancement of Delivery of Brain Tumor Therapies. Zaki Ghali, MG., Srinivasan, VM., Kan, P.[2020]

Low-frequency plane-wave ultrasound contrast imaging (1.5-4 MHz) significantly enhances the detection of microbubbles, yielding a contrast signal that is four times stronger at 1.8 MHz compared to 3.1 MHz, and nine times stronger than higher-frequency probes.

This imaging technique allows for the identification of sub-millimeter blood vessels in tumor models and provides better resilience to motion, suggesting its potential for super-resolution imaging and image-guided therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fast, Low-Frequency Plane-Wave Imaging for Ultrasound Contrast Imaging. Kusunose, J., Caskey, CF.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

First-in-human prospective trial of sonobiopsy in glioblastoma patients using neuronavigation-guided focused ultrasound. [2023]

2. England pubmed.ncbi.nlm.nih.gov

First-in-human prospective trial of sonobiopsy in high-grade glioma patients using neuronavigation-guided focused ultrasound. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Quantitative assessment of tumor enhancement by ultrastable lipid-coated microbubbles as a sonographic contrast agent. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Blood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility Study. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Localized blood-brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions-controlled focused ultrasound. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Focused Ultrasonography-Mediated Blood-Brain Barrier Disruption in the Enhancement of Delivery of Brain Tumor Therapies. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Fast, Low-Frequency Plane-Wave Imaging for Ultrasound Contrast Imaging. [2023]