Multiparametric Ultrasound for the Diagnosis of Clinically Significant Prostate Cancer in Adult Men With Suspected Prostate Cancer

Study Overview
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Brief Summary
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This phase III trial compares the use of contrast-enhanced multiparametric ultrasound (mp-US) to multiparametric magnetic resonance imaging (mp-MRI) for the diagnosis of clinically significant prostate cancer (PCa). A mp-US is a procedure in which a probe that sends out high-energy sound waves is inserted into the rectum. The sound waves are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissue called a sonogram. Perflutren lipid michrosphere (Definity) is a contrast agent that uses microbubbles to enhance ultrasound images of the prostate. Doctors hope to learn if the Definity-enhanced mp-US imaging technique can accurately direct targeted biopsy for the detection of clinically significant prostate cancer when compared to standard of care mp-MRI.

Detailed Description
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PRIMARY OBJECTIVE: I. To demonstrate non-inferiority between the detection rate of clinically significant PCa with 3-dimensional (3D) mp-US + systematic biopsy compared to the detection rate of mp-MRI + systematic biopsy. SECONDARY OBJECTIVES: I. To demonstrate non-inferiority of a biopsy approach utilizing targeted biopsy cores based on mp-US compared with targeted biopsy based on mp-MRI, for detection of clinically significant PCa. II. To construct an optimal logistic regression model to predict the presence of clinically significant PCa based on the mp-US elements as well as the prostate specific antigen (PSA), PSA velocity and any other biological variables (e.g., age). OUTLINE: Patients undergo mp-MRI, receive Definity intravenously (IV), and undergo transrectal mp-US and prostate biopsies on study.

Official Title
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Prostate Cancer Diagnosis by Multiparametric Ultrasound (Clinical)

Conditions
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Prostate Carcinoma

Intervention / Treatment
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* Procedure: ultiparametric Magnetic Resonance Imaging
* Drug: Perflutren lipid microsphere
* Procedure: Transrectal Ultrasound
* Procedure: Biopsy of Prostate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be scheduled for a prostate biopsy, based on an elevated PSA (> 3.0ng/ml) per most recent National Comprehensive Cancer Network (NCCN) guidelines, elevated PSA velocity (> 0.75ng/ml/year), or abnormal digital rectal examination Subject must be able and willing to give written informed consent for a contrast enhanced ultrasound study of the prostate including the additional study biopsies Subject must be a male at least 18 years of age when informed consent is obtained Exclusion Criteria: Participant in a clinical trial involving an investigational drug within the past 30 days Patients with known or suspected hypersensitivity to perflutren, polyethylene glycol (PEG), or any other component of Definity Previous treatment for prostate cancer, including hormone therapy Clinically unstable, severely ill, or moribund as per treating physician

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (mp-MRI, Definity, mp-US, prostate biopsies)<br>Patients undergo mp-MRI, receive Definity IV, and undergo transrectal mp-US and prostate biopsies on study. | Procedure: ultiparametric Magnetic Resonance Imaging<br>* Undergo mp-MRI<br>* Other names: Multiparametric MRI;Drug: Perflutren lipid microsphere<br>* Given IV<br>* Other names: Definity;Procedure: Transrectal Ultrasound<br>* Undergo transrectal mp-US<br>* Other names: TRUS;Procedure: Biopsy of Prostate<br>* Undergo prostate biopsies<br>* Other names: Prostatic Biopsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate cancer (PCa) detection rate of 3-dimensional (3D) multiparametric ultrasound (mp-US) combined with systematic biopsy | Will compare PCa detection rate of 3D mp-US combined with systematic biopsy to detection rate of multiparametric magnetic resonance imaging (mp-MRI) combined with systematic biopsy. Will evaluate paired biopsy data for non-inferiority and superiority endpoints, comparing the detection rate of clinically significant PCa with mp-US + systematic biopsy to the detection rate of mp-MRI + systematic biopsy. This analysis will be repeated using both definitions of clinically significant PCa. Categorical data will be summarized as counts and percentages (or proportions) and continuous data will be summarized with descriptive statistics such as mean, standard deviation (SD), median, and range. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCa detection rate of 3D mp-US | Categorical data will be summarized as counts and percentages (or proportions) and continuous data will be summarized with descriptive statistics such as mean, SD, median, and range. Continuous data will be analyzed using t-tests, or log-rank tests if data are not normally distributed. Variance is expressed through 95% confidence intervals and a significance level of 5% with Bonferroni correction for multiple comparisons will be used to control the group-wise error of the study for individual comparisons. | Up to 2 years | 
| Accuracy of PCa detection by biopsy using the optimal logistical model based around mp-US compared to the optimal logistical model based around mp-MRI | Will evaluate the accuracty of the optimal logistic model combining the mp-US elements as well as the prostate specific antigen, prostate specific antigen velocity and other biological variables. | Up to 2 years |