Ignite Creation Date:
2024-05-06 @ 5:31 PM
Last Modification Date:
2024-10-26 @ 2:30 PM
Study NCT ID:
NCT05333432
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-02-28
First Post:
2022-04-11
Brief Title:
Evaluation of a Multimodal Strategy for Early Diagnosis of Men at High Genetic Risk of Prostate Cancer HRPCa-II
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Evaluation of a Multimodal Strategy for Early Diagnosis of Men at High Genetic Risk of Prostate Cancer
Status:
NOT_YET_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:
HRPCa-II
Brief Summary:
Inherited predisposition to prostate cancer PC has been defined by strict clinical criteria or by genetic profile determined by the presence of a deleterious mutation of deoxyribonucleic acid DNA repair genes related to breastovarian cancers such as BRCA2 BRCA1 or by PC specific variants HOXB13 and 8q24CASC19 But currently recommendations for management and mitigation of PC risk with early screening just emerge for BRCA2 mutation carriers Our study compares a PC screening strategy based on an annual prostate specific antigen PSA test and a clinical examination to a strategy that also includes an annual multiparametric magnetic resonance imaging mpMRI It focus not only on 440 unaffected men carrying the BRCA2 mutation but also on 440 unaffected men member of hereditary PC families with an unidentified mutation or carriers of a mutation of another gene that predisposes to PC for a total number of participants included of 880 This project estimates the benefits and inconveniences to extend the proposed early diagnosis procedure from unaffected men with BRCA2 mutation to all unaffected men meeting criteria of an inherited predisposition It should allow to diagnose PC at a more curable stage and to establish national recommendations for the management of men with high genetic risk of PC useful in clinical routine depending on typology of the genetic risk This project aims to efficiently diagnose them without performing unnecessary biopsies at curable stage of the disease It should reduce their risk of death from this cancer known to be of bad prognosis at an advanced stage
Detailed Description:
Hereditary prostate cancer HPC has been defined by strict clinical criteria and represents 5 of all newly diagnosed prostate cancers PC Inherited predisposition to PC is also genetically determined by the presence of a deleterious mutation of DNA repair genes related to breastovarian cancers BRCA2 BRCA1 ATM or of PC specific variants HOXB13 and 8q24-CASC19
According typology of genetic risk predisposition exposes to an earlier age of onset or a more aggressive form of the disease increasing the risk of death from this cancer
Currently abnormal digital rectal examination DRE and PSA level above 4ngmL are validated as an indication for performing a MRI and prostate biopsies to establish PC diagnosis in its frequent sporadic form Recommendations for the management and the mitigation of PC risk with early screening just emerge for BRCA2 mutation carriers
The unaffected relatives from these HPC families and the carriers of these mutations are potentially at higher risk of PC and need a dedicated screening procedure
This project is based on our experience and the results from the international IMPACT study
Our study will compare this PC screening strategy based on an annual PSA test and a clinical examination to a strategy that also includes an annual multiparametric MRI mpMRI Indeed the PROMIS study has shown that mpMRI is very efficient to detect aggressive PC sensitivity 93 and can identify PC in men with low PSA value This project will estimate the benefits and inconveniences to extend mpMRI at unaffected men with BRCA2 mutation and potentially to all unaffected men meeting criteria of an inherited predisposition It should allow to diagnose PC at a more curable stage and to establish national recommendations for the management of men with high genetic risk of PC useful in clinical routine depending on typology of the genetic risk
Indeed the last French national recommendations HAS Haute Autorité de Santé 2012 in terms of systematic screening for prostate cancer do not include men at high genetic risk Regarding populations of men at high risk the HAS indicates that in the current state of knowledge firstly identifying the groups of men at higher risk of developing prostate cancer is not in itself sufficient to justify screening and secondly that no scientific evidence has been found to justify screening for prostate cancer by assaying PSA in male populations considered to be at higher risk of prostate cancer But these recommendations were published before the results obtained by the IMPACT study
The study focuses on 880 unaffected men at high genetic risk of PC 440 unaffected men carrying the BRCA2 mutation and also 440 unaffected men member of hereditary PC families with an unidentified mutation or carriers of a mutation of another gene that predisposes to PC
Participants are pre-screened by the investigators among the files of participants already followed by the urology andor oncogenetic department Potential participants of the study have been already identified because they are carrying the BRCA2 mutation or are a member of hereditary PC families with an unidentified mutation or carriers of a mutation of another gene that predisposes to PC Screened participants are offered to participate to the study by the urologist or the oncogenetic during a consultation visit which constitutes the inclusion visit
After the inclusion visit participants undergo annual follow-up consultation visits as in standard care during 3 years
Each follow-up visit consists of
an urologic consultation clinical examination DRE and PSA test
a MRI examination The urologic consultation and the MRI examination are scheduled from one year to the next by the urologist
Radiologists perform MRI interpret MRI according to the PIRADS-V2 classification and organize the anonymous export of the MRI for centralized review within 15 days of the MRI examination One of the three referent expert radiologists perform the review of the MRI images within a week In case of disagreement between the local and expert interpretations a third review is performed by one of the two other referent expert radiologists to conclude In case of disagreement between the 2 expert radiologists the highest PIRADS-V2 is considered
In case of abnormal DRE or PSA 3ngmL or PIRADS-V2 2 on mpMRI a prostatic biopsy has to be performed as in routine care The participant continues to be followed by the investigator until the results of biopsy are obtained
If PC is diagnosed from biopsies the referent pathologist of the clinical center makes a standardized report of the pathological analysis of the diagnostic biopsies and organizes anonymous export of scanned slides for centralized review Two expert pathologists while blinded to clinical biological and radiological datas perform the centralized review of positive biopsies at the end of the study Prostate biopsy pathological analysis are assessed according national referential using International Society of Urological Pathology ISUP scoring The participant then leaves the study prematurely and the date of premature discontinuation is the biopsy date
If biopsy is negative the participant remains enrolled in the study and pursue his annual follow-up
The result of the study is to be compared to the interim results of the IMPACT study obtained after 3 years of screening DRE PSA test on non affected men carrying or not BRCA2 mutation
According typology of genetic risk predisposition exposes to an earlier age of onset or a more aggressive form of the disease increasing the risk of death from this cancer
Currently abnormal digital rectal examination DRE and PSA level above 4ngmL are validated as an indication for performing a MRI and prostate biopsies to establish PC diagnosis in its frequent sporadic form Recommendations for the management and the mitigation of PC risk with early screening just emerge for BRCA2 mutation carriers
The unaffected relatives from these HPC families and the carriers of these mutations are potentially at higher risk of PC and need a dedicated screening procedure
This project is based on our experience and the results from the international IMPACT study
Our study will compare this PC screening strategy based on an annual PSA test and a clinical examination to a strategy that also includes an annual multiparametric MRI mpMRI Indeed the PROMIS study has shown that mpMRI is very efficient to detect aggressive PC sensitivity 93 and can identify PC in men with low PSA value This project will estimate the benefits and inconveniences to extend mpMRI at unaffected men with BRCA2 mutation and potentially to all unaffected men meeting criteria of an inherited predisposition It should allow to diagnose PC at a more curable stage and to establish national recommendations for the management of men with high genetic risk of PC useful in clinical routine depending on typology of the genetic risk
Indeed the last French national recommendations HAS Haute Autorité de Santé 2012 in terms of systematic screening for prostate cancer do not include men at high genetic risk Regarding populations of men at high risk the HAS indicates that in the current state of knowledge firstly identifying the groups of men at higher risk of developing prostate cancer is not in itself sufficient to justify screening and secondly that no scientific evidence has been found to justify screening for prostate cancer by assaying PSA in male populations considered to be at higher risk of prostate cancer But these recommendations were published before the results obtained by the IMPACT study
The study focuses on 880 unaffected men at high genetic risk of PC 440 unaffected men carrying the BRCA2 mutation and also 440 unaffected men member of hereditary PC families with an unidentified mutation or carriers of a mutation of another gene that predisposes to PC
Participants are pre-screened by the investigators among the files of participants already followed by the urology andor oncogenetic department Potential participants of the study have been already identified because they are carrying the BRCA2 mutation or are a member of hereditary PC families with an unidentified mutation or carriers of a mutation of another gene that predisposes to PC Screened participants are offered to participate to the study by the urologist or the oncogenetic during a consultation visit which constitutes the inclusion visit
After the inclusion visit participants undergo annual follow-up consultation visits as in standard care during 3 years
Each follow-up visit consists of
an urologic consultation clinical examination DRE and PSA test
a MRI examination The urologic consultation and the MRI examination are scheduled from one year to the next by the urologist
Radiologists perform MRI interpret MRI according to the PIRADS-V2 classification and organize the anonymous export of the MRI for centralized review within 15 days of the MRI examination One of the three referent expert radiologists perform the review of the MRI images within a week In case of disagreement between the local and expert interpretations a third review is performed by one of the two other referent expert radiologists to conclude In case of disagreement between the 2 expert radiologists the highest PIRADS-V2 is considered
In case of abnormal DRE or PSA 3ngmL or PIRADS-V2 2 on mpMRI a prostatic biopsy has to be performed as in routine care The participant continues to be followed by the investigator until the results of biopsy are obtained
If PC is diagnosed from biopsies the referent pathologist of the clinical center makes a standardized report of the pathological analysis of the diagnostic biopsies and organizes anonymous export of scanned slides for centralized review Two expert pathologists while blinded to clinical biological and radiological datas perform the centralized review of positive biopsies at the end of the study Prostate biopsy pathological analysis are assessed according national referential using International Society of Urological Pathology ISUP scoring The participant then leaves the study prematurely and the date of premature discontinuation is the biopsy date
If biopsy is negative the participant remains enrolled in the study and pursue his annual follow-up
The result of the study is to be compared to the interim results of the IMPACT study obtained after 3 years of screening DRE PSA test on non affected men carrying or not BRCA2 mutation
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