Clinical Validity and Utility of Genomic-targeted Chemoprevention of PCa: Aim 4a

This study was designed to compare the efficacy, perception, decision making, and cost-effectiveness of genomic and non-genomic approaches for risk assessment of prostate cancer and for chemoprevention of prostate cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Prostate Cancer, Familial; Hereditary Prostate Cancer
• Intervention / Treatment: Genetic: Genetic Risk Score: Number Format; Genetic: Genetic Risk Score: Number + Pictograph; Behavioral: Family History: Number Format; Behavioral: Family History: Number + Pictograph

Detailed Description

ABSTRACT: This clinical trial registration is focused on Aim 4 within the overall project described in the following.

Prostate cancer (PCa) is the most common cancer among men in the U.S. One important strategy to address this public health concern is to prevent the disease. Two large randomized clinical trials, The Prostate Cancer Prevention Trial (PCPT) and The Reduction by Dutasteride of Prostate Cancer Events (REDUCE), have demonstrated a 23-25% reduction in PCa risk with the use of 5 alpha reductase inhibitors (5ARIs: finasteride and dutasteride). However, 5ARIs have not been widely adopted due, in part, to poor cost-effectiveness. We hypothesize that targeted chemoprevention, based on 1) overall genetic risk [family history (FH) and PCa risk-associated genetic variants], and 2) polymorphisms that interact with 5ARIs, may be more efficacious and cost-effective, and thus more likely to be employed by physicians and their patients. The effectiveness of this genomic-targeted approach needs to be systematically evaluated and compared to non-genomic approaches using evidence-based methods such as those recommended by the EGAPP (Evaluation of Genomic Applications in Practice and Prevention) working group. We have assembled a multidisciplinary research team to address an overarching question of whether a genomic-targeted approach improves outcomes related to chemoprevention of PCa using 5ARIs compared to a non-targeted approach. We will evaluate and compare the efficacy, perception, decision making, and cost-effectiveness of genomic and non-genomic approaches in two existing large randomized clinical trials (Reduction by Dutasteride of Prostate Cancer Events (REDUCE) and Prostate Cancer Prevention Trial (PCPT)), two new study populations of men at risk for PCa, and in a survey of physicians. The unique study design of REDUCE and PCPT, with end-of-study prostate biopsies, allows us to address two critical questions in this study: Prostate Specific Antigen (PSA) detection-bias of PCa risk-associated Single Nucleotide Polymorphisms (SNPs) and efficacy of genomic-targeted chemoprevention of PCa using 5ARIs. We have the following specific aims: 1) assess the clinical validity of PCa risk prediction models using a panel of non PSA detection biased PCa risk-associated SNPs. 2) identify and assess the clinical validity of novel polymorphisms that interact with 5ARIs in reducing PCa diagnosis using both genome-wide and candidate gene approaches, 3) assess the clinical utility of a genomic-targeted approach by comparing its reduction in rates of PCa with non-targeted chemoprevention, 4) compare perception and decision making of physicians and patients for genomic and non-genomic-targeted chemoprevention of PCa, and 5) Compare the cost-effectiveness of genomic and non-genomic-targeted chemoprevention of PCa. Results from this study will provide comprehensive data for evidence-based evaluation by the Center for Disease Control's Evaluation of Genomic Applications in Practice and Prevention (EGAPP) working group, provide a proof of principle study of Comparative Effectiveness Research (CER), and will help build a road map for future Genomic and Personalized Medicine (GPM) in the 21st century.

• Study Type: Interventional
• Enrollment (Actual): 700
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• age 40 to 49 years, self-defined Caucasian background, and no prior prostate specific antigen (PSA) screening nor prostate cancer (PCa) diagnosis.

Exclusion Criteria:

• outside of age range, or not self defined Caucasian background, or a prior history of PSA screening or PCa diagnosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Genetic Risk Score: Number Format; Genetic Risk Score: Number Format Subjects receive genetic risk scores in a number format.	Genetic: Genetic Risk Score: Number Format; Genetic Risk Score: Number + Pictograph Genetic risk score based on validated panel of 46 single nucleotide polymorphisms previously identified to be associated with Prostate Cancer risk by Genome Wide Association Studies, presented to subjects as a number.
Experimental: Genetic Risk Score: Number + Pictograph; Genetic Risk Score: Number + Pictograph Subjects receive genetic risk scores in a number and pictograph format.	Genetic: Genetic Risk Score: Number + Pictograph; Genetic Risk Score: Number + Pictograph Risk information conveyed as either a number or a number + pictograph, depending on randomization group.
Experimental: Family History: Number Format; Family History: Number Format Subjects receive family history risk in a number format.	Behavioral: Family History: Number Format; Family History: Number Format Risk information conveyed as either a number or a number + pictograph, depending on randomization group.
Experimental: Family History: Number + Pictograph; Family History: Number + Pictograph Subjects receive family history risk in a number and pictograph format.	Behavioral: Family History: Number + Pictograph; Family History: Number + Pictograph Risk information conveyed as either a number or a number + pictograph, depending on randomization group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Had Prostate Specific Antigen (PSA) Discussion With Physician at 3 Months, Measured by Survey	Discussion with Physician regarding PSA screening, measured by survey 3 months after provision of risk information	3 months
Number of Participants Who Had PSA Testing at 3 Months, Measured by Survey	PSA screening, measured by survey 3 months after provision of risk information.	3 months
Number of Participants Who Had PSA Testing at 3 Years, Measured by Medical Records	PSA screening, measured by medical records 3 years after provision of risk information.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety, Measured by State-trait Anxiety Inventory (STAI)	Immediate reaction to risk information. Measured by state anxiety scale that assess current feelings "at this moment": 1) not at all, 2) somewhat, 3) moderately so, and 4) very much so. A shortened version of questions 1,3,5,9,11,12,13,15,17, and 19 from STAI form XI were used. Each item, within then STAI is scored on a scale of 1-4 and with 10 items, the possible range of total scores was 10 (lowest anxiety) to 40 (highest anxiety). Lowest scores represent better outcomes.	Baseline
Accuracy of Immediate Recall of Risk Information Measured by Survey	Mean between Immediate recall of risk information and told risk information. Immediate recall is measured by survey question: "Based on the information given to you, what were you told is your chance of developing prostate cancer in your lifetime from 0% to 100% ______ %"	Baseline
Accuracy of Recall of Risk Information at 3 Months Measured by Survey	Mean between recall of risk information at 3 months measured by survey, and told risk information. Recall at 3 months is measured by survey question: "Based on the information given to you, what were you told is your chance of developing prostate cancer in your lifetime from 0% to 100% ______ %"	3 month

Collaborators and Investigators

• Sponsor: NorthShore University HealthSystem
• Collaborators: National Cancer Institute (NCI); Wake Forest University Health Sciences; Van Andel Research Institute; Spectrum Health Medical Group
• Investigators: Principal Investigator: Jianfeng Xu, Dr.P.H., Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: February 28, 2015
• First Submitted That Met QC Criteria: March 5, 2015
• First Posted (Estimate): March 6, 2015

Study Record Updates

• Last Update Posted (Actual): November 22, 2019
• Last Update Submitted That Met QC Criteria: November 4, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Prostate Cancer; Chemoprevention; Prostate-Specific Antigen; Genetic testing; Genetic Counseling; Prostate Specific Antigen; Genomic testing; Predictive Genetic Testing
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: IRB00011784; 1RC2CA148463-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no intent to share individual participant data (IPD). The terms included in the study consent form do not allow sharing of IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No