Ignite Creation Date:
2024-05-06 @ 3:17 PM
Last Modification Date:
2024-10-26 @ 1:46 PM
Study NCT ID:
NCT04583072
Status:
COMPLETED
Last Update Posted:
2023-09-13
First Post:
2020-09-28
Brief Title:
Stockholm3 Validation Study in a Multi-Ethnic Cohort
Sponsor:
Karolinska Institutet
Organization:
Karolinska Institutet
Study Overview
Official Title:
SEPTA Trial Stockholm3 Validation Study in a Multi-Ethnic Cohort for ProsTAte Cancer
Status:
COMPLETED
Status Verified Date:
2024-10
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:
SEPTA
Brief Summary:
Introduction Prostate cancer PCa is the most commonly detected cancer in men and is the second leading cause of cancer death Differences in race and ethnicity have been shown to have differences in PCa incidence detection and outcomes Current prostate cancer screening involves prostatic specific antigen PSA which is a nonspecific protein marker aka kallikrein that can often leads to unnecessary biopsies up to 74 benign biopsies and clinical overdiagnosis with up to 22 clinically insignificant cancer Recently more sophisticated tests have been developed for PCa screening in the United States such as the Prostate Health Index PHI and the 4k kallikrein score as well as clinical models that use information from the patient clinical history However these tests utilize limited serum protein assays and none of the established screening protocols utilize genetic variables to help account for the likely inherited risks as seen in different ethnicities
A recent Swedish prospective population-based study published in the Lancet Oncology developed a unique multivariable biopsy outcome prediction model within a Nordic population of nearly 60000 men This model the Stockholm3 which incorporated plasma protein markers germline DNA SNPs as well as clinical variables was shown to be capable of reducing the number of biopsies by 44 compared to PSA while maintaining adequate sensitivity for detection of PCa
It is unknown whether an approach developed in Sweden that incorporates protein markers genetics clinical variables and genetic ancestry would be beneficial in a racially diverse cohort
Hypothesis The investigators hypothesize that a prospectively studied multiethnic cohort of men with the Stockholm3 test will identify unique and common risk factors that improve prostate cancer detection
Aim To assess the performance of the Stockholm3 test as compared to PSA and to identify unique features associated with PCa in BlackAfrican American n500 Asian n500 WhiteCaucasian Hispanic n500 and WhiteCaucasian Non-Hispanic n500 men
Methods The investigators propose a prospectively identified cohort with participating institutions which have screened positive to undergo a prostate biopsy to have a retrospective analysis the Stockholm3 test and ancestry markers Within this cohort the investigators will examine several predetermined risk factors to investigate their relationship to prostate cancer
This blood sample will be tested for quantitative levels of serum protein markers and DNA will be extracted and will be tested for germline mutations as defined by the Stockholm3 test and other ancestry informative markers Results from the study will be presented in such a way that no individual information will be disclosed
A recent Swedish prospective population-based study published in the Lancet Oncology developed a unique multivariable biopsy outcome prediction model within a Nordic population of nearly 60000 men This model the Stockholm3 which incorporated plasma protein markers germline DNA SNPs as well as clinical variables was shown to be capable of reducing the number of biopsies by 44 compared to PSA while maintaining adequate sensitivity for detection of PCa
It is unknown whether an approach developed in Sweden that incorporates protein markers genetics clinical variables and genetic ancestry would be beneficial in a racially diverse cohort
Hypothesis The investigators hypothesize that a prospectively studied multiethnic cohort of men with the Stockholm3 test will identify unique and common risk factors that improve prostate cancer detection
Aim To assess the performance of the Stockholm3 test as compared to PSA and to identify unique features associated with PCa in BlackAfrican American n500 Asian n500 WhiteCaucasian Hispanic n500 and WhiteCaucasian Non-Hispanic n500 men
Methods The investigators propose a prospectively identified cohort with participating institutions which have screened positive to undergo a prostate biopsy to have a retrospective analysis the Stockholm3 test and ancestry markers Within this cohort the investigators will examine several predetermined risk factors to investigate their relationship to prostate cancer
This blood sample will be tested for quantitative levels of serum protein markers and DNA will be extracted and will be tested for germline mutations as defined by the Stockholm3 test and other ancestry informative markers Results from the study will be presented in such a way that no individual information will be disclosed
Detailed Description:
Study Design and Procedures
The research coordinator will explain the information contained within the consent Additionally patients blood will be drawn prior to their biopsy
Prior to the biopsy blood will be collected in x2 ethylenediaminetetraacetic acid EDTA 4 ml tubes after obtaining consent from the subjects One tube will be immediately centrifuged 10 minutes at 2000G and plasma decanted to a tube without additives this typically produces 15 ml of plasma The decanted tube with plasma and the remaining EDTA tube with whole blood is then frozen and stored at the designated participating institutional site It will be stored at -20 Celsius until being shipped The SEPTA specific blood collection is followed by the following collaborators Uropartners University of Illinois at Chicago University of Chicago Rush Medical Center Montefiore University of Texas Health Science Center of San Antonio Urology Clinics of North Texas University of Southern California Keck School of Medicine Los Angeles County Hospital Stanford University
Additional samples from University Health Network Toronto Northwestern Medicine John H Stroger Jr Hospital of Cook County and Cook County Health System Chicago will be included from biobanked sources which were prospective collected meeting inclusion and exclusion criteria
Patient data will be stored in a REDCap database hosted on Swedens secure server Data will be stored for the duration of the study and 5 years afterwards for data analysis purposes
Consented patients will be tracked by patient logs by each participating institution The medical record number will be collected to keep a consistent identifier for data collection by key site personnel Once all the patient data is recorded the data will be exported from REDCap with the MRN removed There will be no patient identifiers used at the Karolinska Institute or A3P lab The following PHI and non-PHI information will be logged of the patient
PHI
Medical record number MRN
Non-PHI Demographic data
Stockholm3 Identification number
Race
Zip code
Clinical data
Total PSA
Age on sampling date years
Family history of prostate cancer
Use of 5-alpha reductase inhibitors
Earlier biopsy conducted
Prostate volume Prostate volume as measure with US
Digital rectal exam status Benignnormal Noduleinduration felt Asymmetry Not performed
AND
Outcome data - Results from biopsy performed immediately after blood venipuncture ie
Results will be separated into targeted biopsy cores and systematic biopsy cores
Gleason Score 1
Gleason Score 2
Gleason Sum
Cancer length mm total and highest grade
Number of cores
Number of positive cores
Time to perform biopsy after blood draw days
Results from MRI ie Prostate Imaging Reporting Data System PIRADS 0 1 2 3 4 5
Permitted use
To run the Stockholm3 test defined by Gronberg et al AND Ancestry informative genetic markers
Samples will be shipped to the Uppsala based laboratory A23 Laboratory in Sweden for analysis Each patient will have two blood samples plasma and whole blood and will be frozen at -20 Celsius The blood samples will then be tested for quantitative levels of serum protein levels and DNA will be extracted from white blood cells and will be tested for gene and small nucleotide polymorphic SNPs germline mutations and variants
Genotyping will be performed using custom genotyping assays Plasma will be used for protein analysis Plasma protein analysis will be performed using a custom protein assays including total and free PSA human glandular kallikrein 2 hK2 microseminoprotein-beta MSMB and Macrophage inhibitory cytokine 1 MIC-1 PSA will be tested with a commercial assay
Based on the results from the plasma protein analysis the genetic analysis and clinical data the Stockholm3 Risk Score will be calculated The participants samples will be treated in accordance with the regulations of Sweden at the laboratory based in Uppsala Sweden
Results of the tests will not be shared with the patient nor will the results change or impact medical decisions
Expected RisksBenefits
Anticipated Risks
As this is retrospective analysis of deidentified patient information as well as deidentified biospecimens there are few anticipated risks A confidentiality breach as well as loss of privacy are possible however every effort will be made to minimize this risk
Anticipated Benefits
Participants will advance scientific and clinical knowledge Participants will also receive a small payment for the time and involvement in the study
Data Collection and Management Procedures
This study will utilize REDCap Research Electronic Data Capture a software toolset and workflow methodology for electronic collection and management of clinical and research data to collect and store data The Karolinska Institute Information Technology KI-IT Department will be used as a central location for data processing and management REDCap is hosted by KI-IT in the Biomedicum Solnavägen 9 Solna Sweden 17165
Data Analysis
Data analysis will be performed by the PI co-investigators andor key research personnel
Quality Control and Quality Assurance
Key research personnel will be responsible for ensuring all data collected adheres to the protocol
Data and Safety Monitoring
This study is minimal risk and all efforts will be made to ensure there are no confidentiality breaches as well as no loss of privacy
Statistical Considerations
Power analysis This study is being conducted among several sites and thus pooled analysis will be performed Based on the framework developed a two-sided alpha of 005 250 men in each ethnicity gives 80 power to detect 10 percentage points differences in sensitivity andor specificity of the Stockholm3 test across different ethnicities Pooled data from several sites will allow for comparison between non-Hispanic White AfricaBlack Asian and Hispanic White men Within each ethnicity group of 250 men the same sample size gives a 90 power for detecting differences in area under curve AUC between Stockholm3 and PSA for detection of PC that are at least 10 percentage points primary aim
Goal accruement is 500 men within each raceethnicity interim analysis will be performed when 250 men in each raceethnicity is enrolled
Data Analysis Descriptive univariate statistics will be used to compare groups Binary endpoints will be assessed with a logistic regression model Statistical analysis will involve logistic regression modeling AUC calculation calibration analyses and calculation of basic performance characteristics sensitivity specificity and predictive values
Regulatory Requirements
Informed Consent The participants indicate their consent to participate in the study by signing informed consents for accessing medical records conducting genetic research and undergoing venipuncture for blood samples
Subject Confidentiality Data used for this study will be stored in REDCaps and all data transferred between institutions will remain deidentified throughout the study
Unanticipated Problems Any unanticipated problems will be immediately reported to the Site-specific ethical review board by designated research personnel
The research coordinator will explain the information contained within the consent Additionally patients blood will be drawn prior to their biopsy
Prior to the biopsy blood will be collected in x2 ethylenediaminetetraacetic acid EDTA 4 ml tubes after obtaining consent from the subjects One tube will be immediately centrifuged 10 minutes at 2000G and plasma decanted to a tube without additives this typically produces 15 ml of plasma The decanted tube with plasma and the remaining EDTA tube with whole blood is then frozen and stored at the designated participating institutional site It will be stored at -20 Celsius until being shipped The SEPTA specific blood collection is followed by the following collaborators Uropartners University of Illinois at Chicago University of Chicago Rush Medical Center Montefiore University of Texas Health Science Center of San Antonio Urology Clinics of North Texas University of Southern California Keck School of Medicine Los Angeles County Hospital Stanford University
Additional samples from University Health Network Toronto Northwestern Medicine John H Stroger Jr Hospital of Cook County and Cook County Health System Chicago will be included from biobanked sources which were prospective collected meeting inclusion and exclusion criteria
Patient data will be stored in a REDCap database hosted on Swedens secure server Data will be stored for the duration of the study and 5 years afterwards for data analysis purposes
Consented patients will be tracked by patient logs by each participating institution The medical record number will be collected to keep a consistent identifier for data collection by key site personnel Once all the patient data is recorded the data will be exported from REDCap with the MRN removed There will be no patient identifiers used at the Karolinska Institute or A3P lab The following PHI and non-PHI information will be logged of the patient
PHI
Medical record number MRN
Non-PHI Demographic data
Stockholm3 Identification number
Race
Zip code
Clinical data
Total PSA
Age on sampling date years
Family history of prostate cancer
Use of 5-alpha reductase inhibitors
Earlier biopsy conducted
Prostate volume Prostate volume as measure with US
Digital rectal exam status Benignnormal Noduleinduration felt Asymmetry Not performed
AND
Outcome data - Results from biopsy performed immediately after blood venipuncture ie
Results will be separated into targeted biopsy cores and systematic biopsy cores
Gleason Score 1
Gleason Score 2
Gleason Sum
Cancer length mm total and highest grade
Number of cores
Number of positive cores
Time to perform biopsy after blood draw days
Results from MRI ie Prostate Imaging Reporting Data System PIRADS 0 1 2 3 4 5
Permitted use
To run the Stockholm3 test defined by Gronberg et al AND Ancestry informative genetic markers
Samples will be shipped to the Uppsala based laboratory A23 Laboratory in Sweden for analysis Each patient will have two blood samples plasma and whole blood and will be frozen at -20 Celsius The blood samples will then be tested for quantitative levels of serum protein levels and DNA will be extracted from white blood cells and will be tested for gene and small nucleotide polymorphic SNPs germline mutations and variants
Genotyping will be performed using custom genotyping assays Plasma will be used for protein analysis Plasma protein analysis will be performed using a custom protein assays including total and free PSA human glandular kallikrein 2 hK2 microseminoprotein-beta MSMB and Macrophage inhibitory cytokine 1 MIC-1 PSA will be tested with a commercial assay
Based on the results from the plasma protein analysis the genetic analysis and clinical data the Stockholm3 Risk Score will be calculated The participants samples will be treated in accordance with the regulations of Sweden at the laboratory based in Uppsala Sweden
Results of the tests will not be shared with the patient nor will the results change or impact medical decisions
Expected RisksBenefits
Anticipated Risks
As this is retrospective analysis of deidentified patient information as well as deidentified biospecimens there are few anticipated risks A confidentiality breach as well as loss of privacy are possible however every effort will be made to minimize this risk
Anticipated Benefits
Participants will advance scientific and clinical knowledge Participants will also receive a small payment for the time and involvement in the study
Data Collection and Management Procedures
This study will utilize REDCap Research Electronic Data Capture a software toolset and workflow methodology for electronic collection and management of clinical and research data to collect and store data The Karolinska Institute Information Technology KI-IT Department will be used as a central location for data processing and management REDCap is hosted by KI-IT in the Biomedicum Solnavägen 9 Solna Sweden 17165
Data Analysis
Data analysis will be performed by the PI co-investigators andor key research personnel
Quality Control and Quality Assurance
Key research personnel will be responsible for ensuring all data collected adheres to the protocol
Data and Safety Monitoring
This study is minimal risk and all efforts will be made to ensure there are no confidentiality breaches as well as no loss of privacy
Statistical Considerations
Power analysis This study is being conducted among several sites and thus pooled analysis will be performed Based on the framework developed a two-sided alpha of 005 250 men in each ethnicity gives 80 power to detect 10 percentage points differences in sensitivity andor specificity of the Stockholm3 test across different ethnicities Pooled data from several sites will allow for comparison between non-Hispanic White AfricaBlack Asian and Hispanic White men Within each ethnicity group of 250 men the same sample size gives a 90 power for detecting differences in area under curve AUC between Stockholm3 and PSA for detection of PC that are at least 10 percentage points primary aim
Goal accruement is 500 men within each raceethnicity interim analysis will be performed when 250 men in each raceethnicity is enrolled
Data Analysis Descriptive univariate statistics will be used to compare groups Binary endpoints will be assessed with a logistic regression model Statistical analysis will involve logistic regression modeling AUC calculation calibration analyses and calculation of basic performance characteristics sensitivity specificity and predictive values
Regulatory Requirements
Informed Consent The participants indicate their consent to participate in the study by signing informed consents for accessing medical records conducting genetic research and undergoing venipuncture for blood samples
Subject Confidentiality Data used for this study will be stored in REDCaps and all data transferred between institutions will remain deidentified throughout the study
Unanticipated Problems Any unanticipated problems will be immediately reported to the Site-specific ethical review board by designated research personnel
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?:
None
Is an FDA AA801 Violation?:
None