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

NCT ID: NCT02967458

Last Updated: 2025-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-01
• Study Completion Date: 2018-09-20

Brief Summary

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.

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).

Conditions

Prostatic Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Perflutren Lipid Microsphere Intravenous Suspension

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Definity™ (Lantheus Medical Imaging, Inc; N. Billerica, MA)

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Thomas Jefferson University

OTHER

Sponsor Role: lead

Responsible Party

Flemming Forsberg

Professor - Radiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ethan J Halpern, MD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Flemming Forsberg, PhD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Locations

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Countries

United States

References

Halpern EJ, Gomella LG, Forsberg F, McCue PA, Trabulsi EJ. Contrast enhanced transrectal ultrasound for the detection of prostate cancer: a randomized, double-blind trial of dutasteride pretreatment. J Urol. 2012 Nov;188(5):1739-45. doi: 10.1016/j.juro.2012.07.021. Epub 2012 Sep 19.

Reference Type: BACKGROUND

PMID: 22998915 (View on PubMed)

Aigner F, Schafer G, Steiner E, Jaschke W, Horninger W, Herrmann TR, Nagele U, Halpern EJ, Frauscher F. Value of enhanced transrectal ultrasound targeted biopsy for prostate cancer diagnosis: a retrospective data analysis. World J Urol. 2012 Jun;30(3):341-6. doi: 10.1007/s00345-011-0809-6. Epub 2011 Dec 18.

Reference Type: BACKGROUND

PMID: 22179312 (View on PubMed)

Trabulsi EJ, Sackett D, Gomella LG, Halpern EJ. Enhanced transrectal ultrasound modalities in the diagnosis of prostate cancer. Urology. 2010 Nov;76(5):1025-33. doi: 10.1016/j.urology.2010.05.022. Epub 2010 Aug 16.

Reference Type: BACKGROUND

PMID: 20719368 (View on PubMed)

Nelson ED, Slotoroff CB, Gomella LG, Halpern EJ. Targeted biopsy of the prostate: the impact of color Doppler imaging and elastography on prostate cancer detection and Gleason score. Urology. 2007 Dec;70(6):1136-40. doi: 10.1016/j.urology.2007.07.067.

Reference Type: BACKGROUND

PMID: 18158034 (View on PubMed)

Linden RA, Trabulsi EJ, Forsberg F, Gittens PR, Gomella LG, Halpern EJ. Contrast enhanced ultrasound flash replenishment method for directed prostate biopsies. J Urol. 2007 Dec;178(6):2354-8. doi: 10.1016/j.juro.2007.08.022. Epub 2007 Oct 22.

Reference Type: BACKGROUND

PMID: 17936814 (View on PubMed)

Halpern EJ, Ramey JR, Strup SE, Frauscher F, McCue P, Gomella LG. Detection of prostate carcinoma with contrast-enhanced sonography using intermittent harmonic imaging. Cancer. 2005 Dec 1;104(11):2373-83. doi: 10.1002/cncr.21440.

Reference Type: BACKGROUND

PMID: 16240450 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R21CA202214

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JT 8299

Identifier Type: OTHER

Identifier Source: secondary_id

15F.607

Identifier Type: -

Identifier Source: org_study_id