Ignite Creation Date:
2024-05-05 @ 12:11 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00261456
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-04-07
First Post:
2005-12-01
Brief Title:
The IMPACT Study - Identification of Men With a Genetic Predisposition to ProstAte Cancer
Sponsor:
Institute of Cancer Research United Kingdom
Organization:
Institute of Cancer Research United Kingdom
Study Overview
Official Title:
The IMPACT Study - Identification of Men With a Genetic Predisposition to ProstAte Cancer Targeted Screening in Men at Higher Genetic Risk and Controls
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-08
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:
None
Brief Summary:
The IMPACT study is an international targeted prostate screening study of men at increased prostate cancer risk due to the presence of known pathogenic mutations in BRCA1 and BRCA2 genes and Mis-Match Repair genes MLH1 MSH6 MSH2
There are only approximately 150 men with a known BRCA1 or BRCA2 mutation in the UK Research has shown that these men are at an increased risk of developing prostate cancer but more information is needed about the pathogenesis of prostate cancer in this defined group and the role of screening in these men The study will offer annual PSA screening to these men to determine the incidence of prostate cancer in this group The study will also look at new markers of early prostate cancer in this cohort
The power calculations for this study are 850 carriers and 850 controls age-matched men without BRCA12 Mis match repair mutations It is therefore essential to gain international collaboration to meet the target of recruiting 850 men with these known mutations and a control group of 850 men who have tested negative for a known familial mutation
There are only approximately 150 men with a known BRCA1 or BRCA2 mutation in the UK Research has shown that these men are at an increased risk of developing prostate cancer but more information is needed about the pathogenesis of prostate cancer in this defined group and the role of screening in these men The study will offer annual PSA screening to these men to determine the incidence of prostate cancer in this group The study will also look at new markers of early prostate cancer in this cohort
The power calculations for this study are 850 carriers and 850 controls age-matched men without BRCA12 Mis match repair mutations It is therefore essential to gain international collaboration to meet the target of recruiting 850 men with these known mutations and a control group of 850 men who have tested negative for a known familial mutation
Detailed Description:
Prostate cancer is a significant public health problem In the EU approximately 200000 men are diagnosed annually with prostate cancer There are 24000 cases per year in England and Wales and 10000 deaths The incidence is increasing even when screen-detected cancers are considered and within the next few years it will become the most common cancer in UK men
that an alteration in the breast cancer predisposition genes BRCA1 and BRCA2 may predispose to prostate cancer PC and this study will increase this evidence-base There is some evidence at least in BRCA2 carriers that the prostate cancer in these men may be more aggressive and so earlier detection could theoretically reduce mortality It has been reported that unaffected individuals from families with multiple cases of PC show an increased percentage of raised PSA levels but the use of PSA level and its predictive value in healthy males with BRCA12 mutations has not been studied If PSA were to be used as a screening tool in BRCA12 mutation carriers we would need to gain a better understanding of the pathogenesis of PC in these men and determine whether they have a different baseline PSA profile compared with controls
The high prevalence of hormone-dependentsecreting tumours such as breast ovary and prostate in BRCA12 carriers suggests an important role of hormones and their receptors in the development of cancer Androgens and androgen receptors are considered crucial elements in PC pathogenesis Therefore male sex hormones will be measured to determine the hormone profile in BRCA12 carriers compared with a control group There is strong evidence that BRCA12 play an important role in DNA repair and cell cycling Therefore we will investigate abnormalities of the metabolic processes in individuals with a BRCA12 mutation where cell cycling may be abnormal Analysis of proteins proteomics and metabolites metabonomics are powerful approaches to identifying proteins and metabolites involved in cancer formation The analysis of the proteins and metabolites will enable us to investigate the effect of the presence of a BRCA12 mutation and aid in the identification of new biomarkers for prostate cancer
The target population is a group of 850 males who carry a known pathogenic mutation in the BRCA12 genes 500 BRCA1 and 350 BRCA2 These men will be recruited through genetics clinics across the UK and the world A control group of men who have tested negative for a known pathogenic mutation that is running in their family will also be recruited through the genetics clinics
All participants will be invited to attend annually for 5 years for an appointment lasting approximately 30 minutes during which they will discuss the study in detail before giving their written consent agreeing to participate They will have a 50ml blood sample taken and be asked to provide a urine sample every year They will also be required to complete a short family and medical history questionnaire These appointments will either take place at the centre they are registered at at the Royal Marsden Hospital or in their own home depending on the arrangements made with the collaborating consultant and patient preference
The PSA level of all participants will be measured locally If PSA is 30ngml a ten core prostatic biopsy will be offered carried out by a consultant urologist Ten biopsies will be used for diagnostic purposes with two extra biopsy samples taken for research analysis with the patients fully informed written consent prior to the procedure being carried out If any of the ten cores identify the presence of prostate cancer they will receive treatment for this as advised by their local centre The PSA will be quality controlled by batch testing at a reference lab If the value locally was 30ngml but is 3ngml in the reference lab it will be remeasured locally
If high grade Prostatic Intraepithelial Neoplasia PIN is detected or if the sample is inconclusive then a sextant biopsy repeated after 6 weeks will be recommended in accordance with the ERSPC protocol If atypical acini are detected then immediate biopsy will be undertaken
that an alteration in the breast cancer predisposition genes BRCA1 and BRCA2 may predispose to prostate cancer PC and this study will increase this evidence-base There is some evidence at least in BRCA2 carriers that the prostate cancer in these men may be more aggressive and so earlier detection could theoretically reduce mortality It has been reported that unaffected individuals from families with multiple cases of PC show an increased percentage of raised PSA levels but the use of PSA level and its predictive value in healthy males with BRCA12 mutations has not been studied If PSA were to be used as a screening tool in BRCA12 mutation carriers we would need to gain a better understanding of the pathogenesis of PC in these men and determine whether they have a different baseline PSA profile compared with controls
The high prevalence of hormone-dependentsecreting tumours such as breast ovary and prostate in BRCA12 carriers suggests an important role of hormones and their receptors in the development of cancer Androgens and androgen receptors are considered crucial elements in PC pathogenesis Therefore male sex hormones will be measured to determine the hormone profile in BRCA12 carriers compared with a control group There is strong evidence that BRCA12 play an important role in DNA repair and cell cycling Therefore we will investigate abnormalities of the metabolic processes in individuals with a BRCA12 mutation where cell cycling may be abnormal Analysis of proteins proteomics and metabolites metabonomics are powerful approaches to identifying proteins and metabolites involved in cancer formation The analysis of the proteins and metabolites will enable us to investigate the effect of the presence of a BRCA12 mutation and aid in the identification of new biomarkers for prostate cancer
The target population is a group of 850 males who carry a known pathogenic mutation in the BRCA12 genes 500 BRCA1 and 350 BRCA2 These men will be recruited through genetics clinics across the UK and the world A control group of men who have tested negative for a known pathogenic mutation that is running in their family will also be recruited through the genetics clinics
All participants will be invited to attend annually for 5 years for an appointment lasting approximately 30 minutes during which they will discuss the study in detail before giving their written consent agreeing to participate They will have a 50ml blood sample taken and be asked to provide a urine sample every year They will also be required to complete a short family and medical history questionnaire These appointments will either take place at the centre they are registered at at the Royal Marsden Hospital or in their own home depending on the arrangements made with the collaborating consultant and patient preference
The PSA level of all participants will be measured locally If PSA is 30ngml a ten core prostatic biopsy will be offered carried out by a consultant urologist Ten biopsies will be used for diagnostic purposes with two extra biopsy samples taken for research analysis with the patients fully informed written consent prior to the procedure being carried out If any of the ten cores identify the presence of prostate cancer they will receive treatment for this as advised by their local centre The PSA will be quality controlled by batch testing at a reference lab If the value locally was 30ngml but is 3ngml in the reference lab it will be remeasured locally
If high grade Prostatic Intraepithelial Neoplasia PIN is detected or if the sample is inconclusive then a sextant biopsy repeated after 6 weeks will be recommended in accordance with the ERSPC protocol If atypical acini are detected then immediate biopsy will be undertaken
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CCR2598 | OTHER | CCR | None |