Ignite Creation Date:
2024-05-06 @ 7:12 PM
Last Modification Date:
2024-10-26 @ 3:02 PM
Study NCT ID:
NCT05926102
Status:
RECRUITING
Last Update Posted:
2024-02-15
First Post:
2023-06-21
Brief Title:
The Prostate Cancer Genetic Risk and Equitable Screening Study ProGRESS
Sponsor:
VA Office of Research and Development
Organization:
VA Office of Research and Development
Study Overview
Official Title:
The Prostate Cancer Genetic Risk and Equitable Screening Study ProGRESS A Pragmatic Trial of Precision Prostate Cancer Screening
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ProGRESS
Brief Summary:
Prostate cancer is the most common non-skin cancer among Veterans and the second leading cause of male cancer death Current methods of screening men for prostate cancer are inaccurate and cannot identify which men do not have prostate cancer or have low-grade cases that will not cause harm and which men have significant prostate cancer needing treatment False-positive screening tests can result in unnecessary prostate biopsies for men who do not need them However new genetic testing might help identify which men are at highest risk for prostate cancer This study will examine whether a genetic test helps identify men at risk for significant prostate cancer while helping men who are at low risk for prostate cancer avoid unnecessary biopsies If this genetic test proves beneficial it will improve the way that healthcare providers screen male Veterans for prostate cancer
Detailed Description:
Prostate cancer is the most common non-cutaneous cancer in US men and in the Veterans Health Administration VHA 1 in 8 will be diagnosed with the disease in their lifetime Many cases are non-lethal but prostate cancer remains the 2nd leading cause of cancer death among US men representing 25 of all deaths VHA diagnoses 16000 new cases annually and cares for 400000 men living with prostate cancer As a result prostate cancer diagnosis and treatment is a national priority for VHA
A major impediment to reducing the incidence of metastatic prostate cancer and prostate cancer death is the lack of an optimal screening strategy to identify men at high risk Screening with prostate-specific antigen PSA testing modestly reduces prostate cancer deaths but at the cost of overdiagnoses and overtreatment Current screening approaches do not adequately distinguish men without prostate cancer or with low-grade prostate cancer amenable to active surveillance from men with clinically significant prostate cancer who need treatment As a result clinical guidelines do not recommend universal prostate cancer screening including those from the United States Preventive Services Task Force USPSTF and the VHA National Center for Health Promotion and Disease Prevention Still many men undergo screening based on variable and subjective assessments of their raceethnicity family history and other risk factors
A new paradigm of precision screening could improve the benefit-to-harm ratio of screening by implementing screening strategies tailored to an individuals specific genetic profile Due to advances in high-throughput genotyping and sequencing increasingly large and diverse cohort studies and standardization of genetic variant classification germline genetic testing is emerging as a powerful predictor for prostate cancer including metastatic and lethal disease This includes both rare highly penetrant variants and polygenic risk scores PRS which characterize an individuals predisposition to prostate cancer due to common genetic variation Rare and common genetic variation is now an equally powerful predictor of clinically significant disease as self-reported race or family history including in the Million Veteran Program
This clinical trial will evaluate the promise of precision risk stratification to identify men most likely to benefit from prostate cancer screening During the proof-of-concept phase the investigators will achieve the following aims
1 Develop a precision prostate cancer screening intervention consisting of genetic testing for rare variants and a transancestry PRS delivered to participants and their primary care providers along with individualized genetic risk-informed screening recommendations
2 Determine the feasibility of enrolling men aged 55-70 35 of whom are of racialethnic minority groups to a pragmatic randomized clinical trial RCT comparing the precision screening intervention to usual care
3 Perform an interim assessment to determine whether the observed trajectory of negative prostate biopsy event rates is consistent with rates needed to detect a meaningful between-group difference at the end of the 7-year project period
If the investigators demonstrate feasibility of enrollment and adequate event rates during the proof-of-concept phase the RCT will continue to the clinical trial phase to test the following co-primary hypotheses
1 Compared with men in the usual care arm men in the precision screening arm will have a time-to-diagnosis of clinically significant prostate cancer csPCa defined as NCCN classification intermediate risk or higher that is not inferior by a margin of 30 days over a median 4 years of follow-up
a If non-inferiority is demonstrated the investigators will sequentially test the hypothesis that time-to-diagnosis of csPCa is shorter in the precision screening arm than in the usual care arm superiority
2 Compared with usual care men in the precision screening arm overall will undergo fewer negative prostate biopsies over a median 4 years of follow-up
Pre-specified subgroup analyses will test these hypotheses in Black men specifically to evaluate whether this population benefits equally or more from the intervention Enrollees will be followed for additional outcomes including all prostate cancer diagnoses PSA testing prostate MRI rare variants identified preferences for or against prostate cancer screening and health-related quality of life
The investigators expect that precision screening will increase screening among high-risk patients but decrease screening among low- and average-risk patients thereby maintaining or improving overall csPCa detection while improving the population-level benefit-to-harm ratio Rigorous RCT evidence that genetic risk-informed screening maintains the benefits of screening while minimizing the harms of unnecessary procedures and treatments among low-risk men will change clinical practice and policy around prostate cancer screening
A major impediment to reducing the incidence of metastatic prostate cancer and prostate cancer death is the lack of an optimal screening strategy to identify men at high risk Screening with prostate-specific antigen PSA testing modestly reduces prostate cancer deaths but at the cost of overdiagnoses and overtreatment Current screening approaches do not adequately distinguish men without prostate cancer or with low-grade prostate cancer amenable to active surveillance from men with clinically significant prostate cancer who need treatment As a result clinical guidelines do not recommend universal prostate cancer screening including those from the United States Preventive Services Task Force USPSTF and the VHA National Center for Health Promotion and Disease Prevention Still many men undergo screening based on variable and subjective assessments of their raceethnicity family history and other risk factors
A new paradigm of precision screening could improve the benefit-to-harm ratio of screening by implementing screening strategies tailored to an individuals specific genetic profile Due to advances in high-throughput genotyping and sequencing increasingly large and diverse cohort studies and standardization of genetic variant classification germline genetic testing is emerging as a powerful predictor for prostate cancer including metastatic and lethal disease This includes both rare highly penetrant variants and polygenic risk scores PRS which characterize an individuals predisposition to prostate cancer due to common genetic variation Rare and common genetic variation is now an equally powerful predictor of clinically significant disease as self-reported race or family history including in the Million Veteran Program
This clinical trial will evaluate the promise of precision risk stratification to identify men most likely to benefit from prostate cancer screening During the proof-of-concept phase the investigators will achieve the following aims
1 Develop a precision prostate cancer screening intervention consisting of genetic testing for rare variants and a transancestry PRS delivered to participants and their primary care providers along with individualized genetic risk-informed screening recommendations
2 Determine the feasibility of enrolling men aged 55-70 35 of whom are of racialethnic minority groups to a pragmatic randomized clinical trial RCT comparing the precision screening intervention to usual care
3 Perform an interim assessment to determine whether the observed trajectory of negative prostate biopsy event rates is consistent with rates needed to detect a meaningful between-group difference at the end of the 7-year project period
If the investigators demonstrate feasibility of enrollment and adequate event rates during the proof-of-concept phase the RCT will continue to the clinical trial phase to test the following co-primary hypotheses
1 Compared with men in the usual care arm men in the precision screening arm will have a time-to-diagnosis of clinically significant prostate cancer csPCa defined as NCCN classification intermediate risk or higher that is not inferior by a margin of 30 days over a median 4 years of follow-up
a If non-inferiority is demonstrated the investigators will sequentially test the hypothesis that time-to-diagnosis of csPCa is shorter in the precision screening arm than in the usual care arm superiority
2 Compared with usual care men in the precision screening arm overall will undergo fewer negative prostate biopsies over a median 4 years of follow-up
Pre-specified subgroup analyses will test these hypotheses in Black men specifically to evaluate whether this population benefits equally or more from the intervention Enrollees will be followed for additional outcomes including all prostate cancer diagnoses PSA testing prostate MRI rare variants identified preferences for or against prostate cancer screening and health-related quality of life
The investigators expect that precision screening will increase screening among high-risk patients but decrease screening among low- and average-risk patients thereby maintaining or improving overall csPCa detection while improving the population-level benefit-to-harm ratio Rigorous RCT evidence that genetic risk-informed screening maintains the benefits of screening while minimizing the harms of unnecessary procedures and treatments among low-risk men will change clinical practice and policy around prostate cancer screening
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| I01CX002635 | NIH | None | httpsreporternihgovquickSearchI01CX002635 |