Multi-Center Trial of High-resolution Transrectal Ultrasound Versus Standard Low-resolution Transrectal Ultrasound for the Identification of Clinically Significant Prostate Cancer

• Sponsor: Exact Imaging (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02079025
• Collaborator: (none)
• Enrollment: 1,676
• Locations: 5
• Arms: 2
• Duration (Months): 50
• Patients Per Site: 335.2
• Patients Per Site Per Month: 6.7

Study Details

Study Description

Brief Summary

This trial uses a ultra high-resolution ultrasound system and specialized transducer, intended for use in prostate imaging. The system's image resolution is significantly better than the standard of care, due to its higher frequency. This allows the system to visualize suspicious areas and structures, and for greater accuracy for guided biopsy.

The primary objective of this study is to demonstrate that ultra high-resolution transrectal ultrasound (UHR-TRUS) is superior to conventional low-resolution transrectal ultrasound (LR-TRUS) in detecting clinically significant cancer among men without known prostate cancer and with an indication for prostate biopsy.

The secondary objective of this study is to compare the difference in the rate of detection of clinically significant cancer between LR-TRUS and UHR-TRUS, from before investigator training to after investigator training.

The tertiary objective for the investigation is to compare the combined sensitivity and specificity in determining cancer detection overall for image-guided biopsy in UHR-TRUS vs. LR-TRUS.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms; Prostate Cancer; Cancer of the Prostate	Device: High-resolution ultrasound guided prostate biopsy; Device: Standard ultrasound guided prostate biopsy	N/A

Detailed Description

This is a two-arm multi-centre randomized trial of LR-TRUS versus UHR-TRUS for guided prostate biopsies in men with no known history of prostate cancer. This trial will enroll a minimum of 800 and a maximum of 2000 patients with regular interim analyses to determine the trial's final sample size. These numbers are based on predictive probabilities of trial success.

The investigation is designed as a comparative non-blinded analysis of LR-TRUS vs. UHR-TRUS. Participants will be randomized to either high-resolution or low resolution ultrasound with an equal chance of being in either group. The randomization scheme will be stratified by centre.

When a subject arrives at the institution for his biopsy, the Study Coordinator opens a sealed envelope that indicates to the study participant and physician whether the procedure will be performed using LR-TRUS or UHR-TRUS.

All subjects have an indication for prostate biopsy, and thus, inclusion of a non-treatment group would necessitate a group of men not to receive standard of care. As such, there is no control group in the subject population.

Procedures in the study are:

• obtaining informed consent for the subject

• collecting pre-biopsy information and recording it on the case report form (CRF)

• perform biopsy procedure

• record biopsy details in CRF

• prepare biopsy specimens for pathology

Data from CRFs will be stored in a proprietary database that is accessed by a web-based interface, where access is limited to those with login and password. No subject-identifiable information will be entered in the database.

The primary endpoint is the detection of clinically significant prostate cancer, i.e., the number of men with clinically significant prostate cancer determined by pathology review among all men randomized and biopsied. Pathological analysis on 12-core biopsy samples will be the only mechanism used to determine if study subjects have prostate cancer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1676 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Multi-Center Trial of High-resolution Transrectal Ultrasound Versus Standard Low-resolution Transrectal Ultrasound for the Identification of Clinically Significant Prostate Cancer
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: LR-TRUS Low-resolution transrectal ultrasound guided prostate biopsy (standard of care)	Device: Standard ultrasound guided prostate biopsy; Ultrasound guided prostate biopsy using standard of care ultrasound system
Experimental: UHR-TRUS Ultra-high resolution transrectal ultrasound guided prostate biopsy	Device: High-resolution ultrasound guided prostate biopsy; Ultrasound guided prostate biopsy using ultra-high resolution ultrasound system; Other Names: ImagistxProstate Urology Ultrasound System

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Clinically Significant Prostate Cancer [First visit (a patient's involvement in the trial is complete following his biopsy).]

   Pathology analysis of prostate biopsy is reviewed for indication of clinically significant prostate cancer. Interim analyses are planned beginning when 800 patients have been enrolled and after every additional 200 patients are enrolled up to the maximum sample size of 2000 patients.

Secondary Outcome Measures

1. Improvement of an Investigator's Ability to Detect Clinically Significant Cancer Using UHR-TRUS Post-training When Compared to Pre-training [Pre-training refers to all biopsy procedures occurring between initial training and mid-trial PRI-MUS training. Post-training refers to all biopsy procedures performed after mid-trial PRI-MUS training.]

   Comparison of pre- and post-training percentage of participants found to harbor clinically significant prostate cancer within the UHR-TRUS arm of the trial

2. Combined Sensitivity and Specificity in Determining Cancer Detection Overall for Image-guided Biopsy [First visit (a patient's involvement in the trial is complete following his biopsy).]

   Pathology analysis of prostate biopsy is reviewed. Sensitivity of targeted biopsy for each arm will be calculated as the number of targeted biopsy that also found cancer among all targeted biopsies. Specificity of targeted biopsy for each arm will be calculated as the number of non-targeted biopsies that find no cancer among all non-targeted biopsies. Interim analyses are planned beginning when 800 patients have been enrolled and after every additional 200 patients are enrolled up to the maximum sample size of 2000 patients.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 79 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All men > 40 years age and <80 years of age with an indication for a prostate biopsy will be offered inclusion in the study. Typical indications for biopsy include abnormal PSA (prostate specific antigen) and/or abnormal DRE (digital rectal exam).

• PSA<50

• Clinical stage < cT3

Exclusion Criteria:

• Men with a history of prostate cancer

• Men undergoing TRUS-guided prostate biopsy in the OR under anesthesia

• Men with known prostate volume (from prior imaging) of > 60cc

• Men with anorectal abnormalities preventing TRUS-guided prostate biopsy

• Men who are unable to provide their own informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Brady Urological Institution	Baltimore	Maryland	United States	21224
2	Urology of Virgina	Virginia Beach	Virginia	United States	23452
3	Prostate Cancer Centre	Calgary	Alberta	Canada	T2V 1P9
4	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
5	Centre de Recherche sur le Cancer ("CRCEO")	Quebec City	Quebec	Canada	G1R 2J6

Sponsors and Collaborators

• Exact Imaging

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Exact Imaging
• ClinicalTrials.gov Identifier: NCT02079025
• Other Study ID Numbers: 2013-UHR-002
• First Posted: Mar 5, 2014
• Last Update Posted: Feb 26, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Exact Imaging: Prostate Biopsy; Ultrasound guided biopsy of the prostate; High-resolution ultrasound
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	LR-TRUS	UHR-TRUS
Arm/Group Description	Low-resolution transrectal ultrasound guided prostate biopsy (standard of care) Standard ultrasound guided prostate biopsy: Ultrasound guided prostate biopsy using standard of care ultrasound system	Ultra-high resolution transrectal ultrasound guided prostate biopsy High-resolution ultrasound guided prostate biopsy: Ultrasound guided prostate biopsy using ultra-high resolution ultrasound system
Period Title: Overall Study
STARTED	839	837
COMPLETED	839	837
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	LR-TRUS	UHR-TRUS	Total
Arm/Group Description	Low-resolution transrectal ultrasound guided prostate biopsy (standard of care) Standard ultrasound guided prostate biopsy: Ultrasound guided prostate biopsy using standard of care ultrasound system	Ultra-high resolution transrectal ultrasound guided prostate biopsy High-resolution ultrasound guided prostate biopsy: Ultrasound guided prostate biopsy using ultra-high resolution ultrasound system	Total of all reporting groups
Overall Participants	839	837	1676
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.6 (8.67)	62.7 (8.66)	62.7 (8.66)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	839 100%	837 100%	1676 100%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Canada	279 33.3%	272 32.5%	551 32.9%
United States	560 66.7%	565 67.5%	1125 67.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Clinically Significant Prostate Cancer
Description	Pathology analysis of prostate biopsy is reviewed for indication of clinically significant prostate cancer. Interim analyses are planned beginning when 800 patients have been enrolled and after every additional 200 patients are enrolled up to the maximum sample size of 2000 patients.
Time Frame	First visit (a patient's involvement in the trial is complete following his biopsy).

Outcome Measure Data

Analysis Population Description

Intent To Treat includes all subjects, Per Protocol includes only subjects without protocol deviations.

Arm/Group Title	LR-TRUS	UHR-TRUS
Arm/Group Description	Low-resolution transrectal ultrasound guided prostate biopsy (standard of care) Standard ultrasound guided prostate biopsy: Ultrasound guided prostate biopsy using standard of care ultrasound system	Ultra-high resolution transrectal ultrasound guided prostate biopsy High-resolution ultrasound guided prostate biopsy: Ultrasound guided prostate biopsy using ultra-high resolution ultrasound system
Measure Participants	839	837
Intent to Treat	36.6 4.4%	34.6 4.1%
Per Protocol	36.6 4.4%	43.7 5.2%

2. Secondary Outcome

Title	Improvement of an Investigator's Ability to Detect Clinically Significant Cancer Using UHR-TRUS Post-training When Compared to Pre-training
Description	Comparison of pre- and post-training percentage of participants found to harbor clinically significant prostate cancer within the UHR-TRUS arm of the trial
Time Frame	Pre-training refers to all biopsy procedures occurring between initial training and mid-trial PRI-MUS training. Post-training refers to all biopsy procedures performed after mid-trial PRI-MUS training.

Outcome Measure Data

Analysis Population Description

Pre and post-training detection rate for csPCa for the UHR-TRUS arm only (as investigators received additional training on this imaging modality)

Arm/Group Title	UHR-TRUS
Arm/Group Description	Ultra-high resolution transrectal ultrasound guided prostate biopsy High-resolution ultrasound guided prostate biopsy: Ultrasound guided prostate biopsy using ultra-high resolution ultrasound system
Measure Participants	837
Pre-Training	32.4
Post-Training	39.0

3. Secondary Outcome

Title	Combined Sensitivity and Specificity in Determining Cancer Detection Overall for Image-guided Biopsy
Description	Pathology analysis of prostate biopsy is reviewed. Sensitivity of targeted biopsy for each arm will be calculated as the number of targeted biopsy that also found cancer among all targeted biopsies. Specificity of targeted biopsy for each arm will be calculated as the number of non-targeted biopsies that find no cancer among all non-targeted biopsies. Interim analyses are planned beginning when 800 patients have been enrolled and after every additional 200 patients are enrolled up to the maximum sample size of 2000 patients.
Time Frame	First visit (a patient's involvement in the trial is complete following his biopsy).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LR-TRUS	UHR-TRUS
Arm/Group Description	Low-resolution transrectal ultrasound guided prostate biopsy (standard of care) Standard ultrasound guided prostate biopsy: Ultrasound guided prostate biopsy using standard of care ultrasound system	Ultra-high resolution transrectal ultrasound guided prostate biopsy High-resolution ultrasound guided prostate biopsy: Ultrasound guided prostate biopsy using ultra-high resolution ultrasound system
Measure Participants	839	837
Measure Post-training biopsy samples	3372	3384
Sensitivity	38.0	60.8
Specificity	89.5	63.2

Adverse Events

Arm/Group Title	LR-TRUS		UHR-TRUS
Arm/Group Description	Low-resolution transrectal ultrasound guided prostate biopsy (standard of care) Standard ultrasound guided prostate biopsy: Ultrasound guided prostate biopsy using standard of care ultrasound system		Ultra-high resolution transrectal ultrasound guided prostate biopsy High-resolution ultrasound guided prostate biopsy: Ultrasound guided prostate biopsy using ultra-high resolution ultrasound system
All Cause Mortality
	LR-TRUS		UHR-TRUS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	LR-TRUS		UHR-TRUS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/839 (0.4%)		3/837 (0.4%)
Infections and infestations
post-biopsy bacteremia	3/839 (0.4%)	3	3/837 (0.4%)	3
Other (Not Including Serious) Adverse Events
	LR-TRUS		UHR-TRUS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/839 (0%)		0/837 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.