Sonobiopsy for Noninvasive and Sensitive Detection of Glioblastoma

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.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma; Glioblastoma Multiforme
• Intervention / Treatment: Device: Sonobiopsy; Procedure: Research blood; Genetic: Cancer Personalized Profiling; Device: Definity®

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Albert Kim, M.D.; Phone Number: 314-747-6561; Email: alberthkim@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Eric Leuthardt, M.D.
      • Sub-Investigator: Hong Chen, Ph.D.
      • Contact: Albert Kim, M.D.; Phone Number: 314-747-6561; Email: alberthkim@wustl.edu
      • Principal Investigator: Albert Kim, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must be newly diagnosed with a lesion in the brain with imaging characteristics consistent with glioblastoma multiforme. Scan must have occurred no more than 28 days prior to enrollment.
• Lesion must be > 3 cm in maximal dimension on MRI.
• Lesion must be in the supratentorial space within 5 cm of the cortical surface.
• Lesion must be gadolinium enhancing.
• Low grade tumors and metastatic tumors
• Recurrent brain tumors and/or radiation necrosis
• Must be planning to undergo surgical resection of the tumor.
• Must be at least 18 years old.
• Patients with recurrent GBM who are planning to undergo surgical resection or laser ablation of the recurrent tumor. Recurrence must be confirmed on MRI performed no more than 28 days prior to enrollment.

Exclusion Criteria:

• Contraindication to MRI.
• Previous cranial surgery.
• Previous history of cancer and/or cancer treatments.
• Coagulopathy within 14 days of enrollment defined as PT/PTT outside of normal parameters and platelets < 100,000/mcL.
• Physical skull defect of any kind.
• Ferrous material in the scalp or skull.
• Scalp or skin disease that limits contact with the ultrasound probe.
• Enrolled in another clinical trial where intervention is administered prior to surgery.
• Known hypersensitivity to polyethylene glycol.
• Known unstable cardiopulmonary condition (e.g. acute myocardial infarction, acute coronary artery syndromes, worsening or unstable congestive heart failure, serious ventricular arrhythmias).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sonobiopsy; 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.

Device: Sonobiopsy; Ultrasound combined with microbubbles to facilitate sampling of biomarkers from brain tumors via blood-based liquid biopsy; Procedure: Research blood; No more than 10 minutes prior to ultrasound sonication, 10 minutes after ultrasound sonication, 30 minutes after ultrasound sonication (optional at the discretion of the PI), and 60 minutes after ultrasound sonication (optional at the discretion of the PI); Genetic: Cancer Personalized Profiling; Cancer Personalized Profiling by deep Sequencing will be used to compare the frequency of tumor-specific variants in the blood before and after sonobiopsy.; Device: Definity®; Being used off-label in this trial; Other Names: Definity® microbubbles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of sonobiopsy as measured by change in ctDNA level	The feasibility of sonobiopsy will be demonstrated by an increase in the amount of ctDNA in the blood samples acquired post than prior sonobiopsy in at least 50% of the patients.	Day 1
Number of matched mutations between the post-sonobiopsy sample and the tumor tissue sample	The agreement of the post-sonobiopsy sample mutation detected in the blood with a variant identified in the tumor tissue will be compared using a kappa statistic.	Day 1

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Albert Kim, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2022
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: February 11, 2022
• First Submitted That Met QC Criteria: March 4, 2022
• First Posted (Actual): March 16, 2022

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: 202202025; R01CA276174 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No