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

Prostatic Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02967458
• Other study ID #: 15F.607
• Secondary ID: R21CA202214
• Status: Completed
• Phase: Phase 2
• Start date: February 1, 2017
• Est. completion date: September 20, 2018

Study information

• Verified date: March 2024
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: September 20, 2018
• Est. primary completion date: February 1, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Prostatic Neoplasm
• Prostatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Thomas Jefferson University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects Whose Prostate Cancer Was Detected With Subharmonic Imaging	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
Primary	Percentage of Biopsy Cores in Which Prostate Cancer Was Detected Using Subharmonic Imaging	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
Primary	Percentage of Subjects With Previously Unidentified Prostate Cancer Using Magnetic Resonance Imaging	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