Clinical trial NCT02967458: Detection of High Grade Prostate Cancer With Subharmonic Ultrasound Imaging, A Pilot Study
Official title: Detection of High Grade Prostate Cancer With Subharmonic Ultrasound Imaging, A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostatic Neoplasm
Keywords: prostate cancer
prostate ultrasound
subharmonic imaging
prostate biopsy
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-11-18
Enrollment: 55
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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).

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.

Primary outcomes:
measure: Percentage of Subjects Whose Prostate Cancer Was Detected With Subharmonic Imaging
timeFrame: One week from baseline
measure: Percentage of Biopsy Cores in Which Prostate Cancer Was Detected Using Subharmonic Imaging
timeFrame: One week from baseline
measure: Percentage of Subjects With Previously Unidentified Prostate Cancer Using Magnetic Resonance Imaging
timeFrame: One week from baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
Study officials:
affiliation: Thomas Jefferson University
name: Ethan J Halpern, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Thomas Jefferson University
name: Flemming Forsberg, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.
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.
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.