Trial Title:
Polygenic Risk Stratification Combined With mpMRI to Identify Clinically Relevant Prostate Cancer
NCT ID:
NCT06398639
Condition:
Prostate Cancer
Polygenic Risk Score
Conditions: Official terms:
Prostatic Neoplasms
Genetic Risk Score
Conditions: Keywords:
Polygenic Risk Score
Prostate Cancer
Prostate Cancer Screening
Multiparametric MRI
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Screening
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
Polygenic Risk Score (PRS)
Description:
Participants will be put into PRS cohorts based on their genetic data.
All participants enrolled into the study will receive a PSA screening test and an mpMRI,
regardless of their polygenic risk score.
Arm group label:
High Risk Cohort
Arm group label:
Intermediate Risk Cohort
Arm group label:
Low Risk Cohort
Summary:
The goal of this clinical trial is to evaluate a screening method to detect clinically
relevant prostate cancer. This clinical trial is using genetic data to determine a man's
risk of cancer, together with multiparametric magnetic resonance imaging (mpMRI) to
identify men with higher grade cancer.
The main questions it aims to answer are:
- If genetic data related to prostate cancer used with MRI can identify higher-grade,
potentially fatal prostate cancer
- What age a MRI is useful clinically for prostate cancer screening
- If deep learning methods used with MRI when the genetic risk of the man is known can
more accurately predict significant cancers
Participants will:
- Get a prostate specific antigen (PSA) blood test
- Get an mpMRI
- Get the results of their genetic data to determine if they are considered high-,
intermediate-, or low-risk for prostate cancer based on the trials genetic testing
- Follow-up for this trial based on the participants risk and findings from the PSA
test and mpMRI
Detailed description:
Background:
- Prostate cancer is the most commonly diagnosed cancer among men in the United States
- Prostate cancer screening using the marker prostate-specific antigen (PSA) is
controversial
- PSA based screening is less effective, at least in part, because it rests on
screening the entire population
- Polygenic risk scores stratify men based on their prostate cancer genetic
predisposition and may improve population level screening programs by focusing on
men with higher risk of disease and sparing low risk men
- It is critical that studies aiming to translate the development of an
early-detection strategy are conducted within a diverse patient population to
address prostate cancer mortality disparities
Study Design:
- Plan to accrue 1,500 participants from both established biobanks and primary care
offices
- Participants will get an initial PSA screening blood test and an mpMRI
- Participants will have their polygenic risk score determined from genome-wide
association study (GWAS) data
- Participant follow-up will be determined by PRS results, as well as if there are
abnormal findings on their PSA screening and/or mpMRI
Objectives:
- To evaluate a screening algorithm to detect clinically relevant prostate cancer
(Gleason score ≥7) using genetic data (PRS) to determine risk of cancer and mpMRI to
identify men with higher grade cancer
- To determine optimal age to begin screening using PRS and mpMRI
- To determine if rare variants in DNA repair enzymes could help refine screening
- To determine if deep learning methods applied to mpMRI and informed by genetic risk
can more accurately predict significant cancers
Prostate cancer screening using prostate specific antigen (PSA) is controversial. On the
one hand, there is a reduction in prostate cancer mortality associated with screening. On
the other, there is clear evidence that widespread and indiscriminate PSA based screening
has led to over diagnosis and over treatment of prostate cancer. In part this is due to
indiscriminate screening of all men, not just those at risk. Development and
implementation of a screening strategy specifically targeting men at risk for potentially
harmful prostate cancer, while sparing low risk men the burdens of screening, is urgently
needed.
The investigators believe that integration of genetic testing and multiparametric MRI
(mpMRI) will dramatically improve screening. Polygenic risk scores (PRS) have been
developed to determine an individual's risk of prostate cancer and attempts have been
made to create risk scores for clinically relevant disease. mpMRI has been established as
an aid in differentiating clinically relevant from indolent prostate cancer.
Our scientific premise is that an integrated approach which leverages the strengths of
both genetics and mpMRI will do more than simply risk stratify men into those at risk for
and not at risk for prostate cancer; the investigators will stratify a population of men
into those with and those without clinically relevant prostate cancer. The investigators
hypothesize that genetic testing to first identify patients at risk of prostate cancer
followed by mpMRI to determine who likely has clinically relevant disease represents an
optimal strategy.
This study will determine if a polygenic risk score can be used in conjunction with mpMRI
to identify Gleason score ≥7 cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- They must have the ability to understand and the willingness to sign a written
information consent document.
- Estimated life expectancy of greater than 10 years.
- No history of prostate cancer.
- Participants must be between 40-69 years of age. This is the age at which screening
for prostate cancer is recommended. This is due to younger patients not being at
risk for the disease and older patients not benefiting from diagnosis.
- No biopsy for prostate cancer within the past 5 years.
- No prostate MRI within the past 5 years.
Exclusion Criteria:
- Unwillingness to sign the informed consent form.
- Contraindication to biopsy such as uncorrectable bleeding or coagulation disorder.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit the safety of
a biopsy and/or surgery.
- Unable to undergo an MRI.
Gender:
Male
Minimum age:
40 Years
Maximum age:
69 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
Howard University Hospital
Address:
City:
Washington
Zip:
20060
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Pamela Coleman, MD
Investigator:
Last name:
Tamaro S Hudson, PhD, MPH
Email:
Sub-Investigator
Facility:
Name:
National Cancer Institute
Address:
City:
Bethesda
Zip:
20814
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Peter A Pinto, MD
Phone:
204-858-7200
Email:
pintop@mail.nih.gov
Investigator:
Last name:
Ismail B Turkbey, MD
Email:
Sub-Investigator
Investigator:
Last name:
Peter L Choyke, MD, FACR
Email:
Sub-Investigator
Facility:
Name:
Walter Reed National Military Medical Center
Address:
City:
Bethesda
Zip:
20814
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Gregory T Chesnut, MD
Phone:
301-319-2900
Email:
gregory.chesnut@usuhs.edu
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02155
Country:
United States
Status:
Recruiting
Contact:
Last name:
Adam S Kibel, MD, MHCM
Phone:
617-525-7697
Email:
akibel@bwh.harvard.edu
Start date:
May 7, 2024
Completion date:
April 30, 2030
Lead sponsor:
Agency:
Adam S. Kibel, MD
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Brigham and Women's Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06398639
