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

NCT ID: NCT02381015

Last Updated: 2019-11-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

700 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-06-30

Study Completion Date

2012-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Prostate Cancer Prostate Cancer, Familial Hereditary Prostate Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Genetic Risk Score: Number Format

Genetic Risk Score: Number Format Subjects receive genetic risk scores in a number format.

Group Type EXPERIMENTAL

Genetic Risk Score: Number Format

Intervention Type GENETIC

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.

Genetic Risk Score: Number + Pictograph

Genetic Risk Score: Number + Pictograph Subjects receive genetic risk scores in a number and pictograph format.

Group Type EXPERIMENTAL

Genetic Risk Score: Number + Pictograph

Intervention Type GENETIC

Genetic Risk Score: Number + Pictograph Risk information conveyed as either a number or a number + pictograph, depending on randomization group.

Family History: Number Format

Family History: Number Format Subjects receive family history risk in a number format.

Group Type EXPERIMENTAL

Family History: Number Format

Intervention Type BEHAVIORAL

Family History: Number Format Risk information conveyed as either a number or a number + pictograph, depending on randomization group.

Family History: Number + Pictograph

Family History: Number + Pictograph Subjects receive family history risk in a number and pictograph format.

Group Type EXPERIMENTAL

Family History: Number + Pictograph

Intervention Type BEHAVIORAL

Family History: Number + Pictograph Risk information conveyed as either a number or a number + pictograph, depending on randomization group.

Interventions

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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.

Intervention Type 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.

Intervention Type GENETIC

Family History: Number Format

Family History: Number Format Risk information conveyed as either a number or a number + pictograph, depending on randomization group.

Intervention Type BEHAVIORAL

Family History: Number + Pictograph

Family History: Number + Pictograph Risk information conveyed as either a number or a number + pictograph, depending on randomization group.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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
Minimum Eligible Age

40 Years

Maximum Eligible Age

49 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Van Andel Research Institute

OTHER

Sponsor Role collaborator

Spectrum Health Medical Group

UNKNOWN

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role collaborator

Endeavor Health

OTHER

Sponsor Role lead

Responsible Party

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Jianfeng Xu

Professor of Human Genomics and Personalized Medicine, Epidemiology, Cancer Biology, and Urology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jianfeng Xu, Dr.P.H.

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Other Identifiers

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1RC2CA148463-01

Identifier Type: NIH

Identifier Source: secondary_id

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IRB00011784

Identifier Type: -

Identifier Source: org_study_id

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