Detection of High Grade Prostate Cancer With Subharmonic Ultrasound Imaging, A Pilot Study

March 7, 2024 updated by: Flemming Forsberg, Thomas Jefferson University

This is a phase II single center study using contrast-enhanced ultrasound to identify aggressive forms of prostate cancer with subharmonic imaging.

The following are the study objectives:

  1. To implement subharmonic imaging technology on a transrectal probe suitable for prostate imaging and biopsy
  2. To demonstrate visualization of prostatic vascularity using subharmonic contrast-enhanced imaging.
  3. To provide a preliminary estimate of the diagnostic accuracy of contrast-enhanced subharmonic imaging for detection of clinically significant PCa.

The study will include 50 subjects who are scheduled for prostate biopsy. Each subject will receive an intravenous infusion of microbubble contrast material immediately prior to a prostate biopsy procedure. The study will demonstrate whether subharmonic imaging with a microbubble contrast agent allows for detection of clinically significant prostate cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background: Prostate cancer (PCa) is the most frequently diagnosed cancer among American males, accounting for 27 % of new cancer diagnoses, but it is directly responsible for only 9.5 % of cancer related deaths. Two recently published clinical trials suggest that overdiagnosis and overtreatment of potentially insignificant cancer is a major drawback of prostate cancer screening, and point to the need for a more specific screening tool that can identify clinically significant prostate cancer. The US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial failed to show a mortality benefit from screening and treatment of prostate cancer. The European Randomized Study of Screening for Prostate Cancer (ERSPC) suggests that with the current standard of care, 1410 men must be screened and 48 additional cases of prostate cancer treated to prevent one death from prostate cancer. Based upon these trials, the U.S. Preventive Services Task Force (USPSTF) has issued a grade "D" recommendation against PSA-based screening for PCa.

Contrast-Enhanced Ultrasound: Recent studies have demonstrated that contrast-enhanced harmonic imaging (HI) can identify enhancement related to vascular flow in higher grade PCa, and that HI can selectively detect patients with "clinically significant" PCa that are most likely to benefit from therapy. Subharmonic imaging (SHI) is a newer technology for contrast-enhanced ultrasound imaging that provides a 10-fold improvement in the signal to background ratio for visualization of small vascular structures, but has not been previously implemented on a transrectal ultrasound probe. SHI of the prostate is expected to advance the imaging of prostatic neovascularity and to improve selective biopsy of clinically significant PCa.

Objective: To adapt SHI to a transrectal probe appropriate for prostate imaging and biopsy (over the first 6 months of this study). The subsequent 18 month pilot clinical study will enroll 50 participants who have a clinical indication for prostate biopsy to quantify SHI for the detection of clinically significant PCa (defined as: Gleason score ≥ 7, a single core with > 50 % involvement, or > 25 % of biopsy cores positive for PCa).

Approach: Each participant will undergo a transrectal ultrasound evaluation of the prostate with conventional grayscale and color Doppler imaging, as well as contrast-enhanced imaging with color Doppler, HI and SHI approaches. Imaging results from each of these techniques will be recorded, but only the SHI findings will be used to guide a targeted biopsy of the prostate. A maximum of 6 targeted biopsy cores will be obtained from each participant, based upon suspicious areas identified with SHI. Following the targeted biopsy, each participant will also receive a 12-part systematic biopsy consisting of 6 laterally directed biopsy cores and 6 medially directed biopsy cores. The pilot study is designed to estimate the detection of clinically significant cancer that will be obtained with targeted biopsy based upon SHI along with the medially directed systematic sextant biopsy cores (≤ 12 cores total).

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Subject must be scheduled for a clinically indicated needle biopsy of the prostate based upon an elevated PSA, abnormal digital rectal examination, or based upon active surveillance of prostate cancer.
  2. Subject must be able and willing to give written informed consent for a contrast enhanced ultrasound study of the prostate.
  3. Subject must be a male at least 18 years of age when informed consent is obtained.
  4. Subject must have a life expectancy that exceeds the duration of the clinical trial.

Exclusion Criteria:

  1. Participant in a clinical trial involving an investigational drug within the past 30 days.
  2. Prior allergic reaction to the ultrasound contrast agent Definity™
  3. Previous treatment for PCa.
  4. Clinically unstable, severely ill, or moribund.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Prostate Biopsy Patients
Fifty patients who are scheduled for a clinically indicated prostate biopsy, and who are able to undergo contrast enhanced transrectal ultrasound will be included in this single arm study. Each of the study subjects will receive in intravenous infusion of a microbubble contrast agent known as Definity™, (Perflutren Lipid Microsphere, Lantheus Medical Imaging, Inc; N. Billerica, MA). Based upon our previous experience, two vials of Perflutren Lipid Microsphere will be mixed and diluted in 50 ml of normal saline, yielding a concentration of 49.4 μl/ml. For the purpose of contrast-enhanced imaging, Perflutren Lipid Microsphere will be infused over approximately 10-12 minutes, during which time ultrasound imaging and biopsy will be performed.
Drug: Perflutren Lipid Microsphere Intravenous Suspension
The intravenous administration of Perflutren Lipid Microsphere will provide enhancement of vascular tissue when performing subharmonic prostate ultrasound imaging. This enhancement will be used to guide targeted biopsy of the prostate to vascular areas which are more likely to contain aggressive prostate cancer.
Other Names:
  • Definity™ (Lantheus Medical Imaging, Inc; N. Billerica, MA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Subjects Whose Prostate Cancer Was Detected With Subharmonic Imaging
Time Frame: One week from baseline
The initial phase of the trial will develop and test subharmonic imaging to demonstrate enhanced visualization of prostate vascularity in all study participants. We will report the percentage of study subjects in whom visualization of prostate vascularity is increased with subharmonic imaging.
One week from baseline
Percentage of Biopsy Cores in Which Prostate Cancer Was Detected Using Subharmonic Imaging
Time Frame: One week from baseline
Study subjects will be scanned with subharmonic imaging during infusion of the microbubble contrast agent. Imaging results will be compared to pathology on prostate biopsy.
One week from baseline
Percentage of Subjects With Previously Unidentified Prostate Cancer Using Magnetic Resonance Imaging
Time Frame: One week from baseline
Study subjects will be scanned with subharmonic imaging during infusion of the microbubble contrast agent. Imaging results will be compared to pathology on prostate biopsy.
One week from baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Thomas Jefferson University

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Ethan J Halpern, MD, Thomas Jefferson University
  • Principal Investigator: Flemming Forsberg, PhD, Thomas Jefferson University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2017

Primary Completion (Actual)

February 1, 2018

Study Completion (Actual)

September 20, 2018

Study Registration Dates

First Submitted

November 16, 2016

First Submitted That Met QC Criteria

November 16, 2016

First Posted (Estimated)

November 18, 2016

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 7, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15F.607
  • R21CA202214 (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

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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