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The PROFILE Study: Germline Genetic Profiling: Correlation With Targeted Prostate Cancer Screening and Treatment (PROFILE)

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ClinicalTrials.gov Identifier: NCT02543905
Recruitment Status : Recruiting
First Posted : September 7, 2015
Last Update Posted : June 10, 2021
Sponsor:
Collaborators:
Royal Marsden NHS Foundation Trust
University of Cambridge
University of Oxford
Queen Mary University of London
Information provided by (Responsible Party):
Institute of Cancer Research, United Kingdom

Brief Summary:
Prostate cancer is now the commonest cancer in men in the Western world, with over 49,000 new cases diagnosed each year and a lifetime risk of 1 in 11 in the United Kingdom. Prostate cancer (PrCa) can run in some families and research studies have identified several genetic changes in Caucasian populations that are thought to increase the risk of developing prostate cancer. Other studies have shown that men from certain ethnic groups also have a higher risk of prostate cancer, and this includes men of black African or Caribbean descent. This study aims to look at men with a higher risk of prostate cancer based on their ethnicity or family history to see whether any of these genetic changes are present in their DNA (genetic material) and whether this could be a helpful screening tool in prostate cancer screening programmes. It is thought that many genetic changes are involved in the development of prostate cancer and research is being carried out worldwide to identify these genetic changes. Some of these changes may cause a very slight increase in prostate cancer risk while others may cause a much larger increase in risk of developing prostate cancer. The investigators will invite (i) Caucasian men with a family history of prostate cancer; (ii) men of black African or Caribbean descent; and (iii) men of any ethnicity who have been found to have inherited a gene mutation that increases risk of prostate cancer for targeted prostate screening (Prostate Specific Antigen (PSA) testing, MRI and a biopsy of the prostate gland) and genetic profiling. The outcome of these prostate cancer screening investigations will be compared with the genetic profiles of those taking part in the study in order to look for certain genetic changes in the gene code that are thought to increase prostate cancer risk. This research will help us to determine what the role of such genetic profiling is in a prostate cancer screening programme and if it helps identify men at high prostate cancer risk.

Condition or disease Intervention/treatment
Prostate Cancer Prostate Biopsy Genetic Counselling Genetic Markers Procedure: Prostate MRI and Biopsy

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Study Type : Observational
Estimated Enrollment : 1050 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The PROFILE Study: Germline Genetic Profiling: Correlation With Targeted Prostate Cancer Screening and Treatment
Actual Study Start Date : March 9, 2015
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Family History Cohort

Caucasian men with a family history of prostate cancer defined as:

  • Men with a first degree relative (or second degree if through female line) with histologically or death certificate proven PrCa diagnosed at <70 years
  • Men with two relatives on the same side of the family with histologically or death certificate proven PrCa where at least one is diagnosed at <70 years
  • Men with three relatives on the same side of the family with histologically or death certificate proven PrCa diagnosed at any age
Procedure: Prostate MRI and Biopsy
All men will be offered a MRI and prostate biopsy and they can either opt to undergo these procedures at baseline irrespective of PSA level at baseline or they can undergo PSA-only screening until clinically indicated based on an age-defined PSA threshold, at which point, they will undergo prostate MRI and biopsy once their PSA reaches the threshold.

Black African / Black Caribbean Cohort

Men of black African or black Caribbean ancestry defined as:

Both parents and all 4 grandparents from that origin.

Procedure: Prostate MRI and Biopsy
All men will be offered a MRI and prostate biopsy and they can either opt to undergo these procedures at baseline irrespective of PSA level at baseline or they can undergo PSA-only screening until clinically indicated based on an age-defined PSA threshold, at which point, they will undergo prostate MRI and biopsy once their PSA reaches the threshold.

High-risk gene mutation cohort
Men of any ethnicity who have been found to have inherited a gene mutation that increases risk of prostate cancer (gene mutation including BRCA1, BRCA2, ATM, PALB2, MLH1, MSH2, MSH6, CHEK2 and other DNA repair gene mutations as listed in the study protocol).
Procedure: Prostate MRI and Biopsy
All men will be offered a MRI and prostate biopsy and they can either opt to undergo these procedures at baseline irrespective of PSA level at baseline or they can undergo PSA-only screening until clinically indicated based on an age-defined PSA threshold, at which point, they will undergo prostate MRI and biopsy once their PSA reaches the threshold.




Primary Outcome Measures :
  1. The association of specific genetic profiles and biomarkers to predict outcome of prostate screening in men at higher genetic risk [ Time Frame: 5 years ]
    To investigate the role of targeted prostate cancer screening in men at higher genetic risk (i.e. family history, ethnicity, gene mutation status), its association with specific genetic profiles and biomarkers as predictive tools of the risk of developing prostate cancer and to correlate these with genetic risk.


Secondary Outcome Measures :
  1. The incidence and aggressiveness of prostate cancer in men at higher genetic risk. [ Time Frame: 5 years ]
    To determine the incidence and aggressiveness of prostate cancer in these men at a higher genetic risk.

  2. The association of Diffusion Weighted MRI (DW-MRI) findings with prostate biopsy results. [ Time Frame: 5 years ]
    To determine whether imaging techniques such MRI can be used to identify prostate cancer when compared to prostate biopsy results.

  3. The incidence of abnormal imaging (using 3D ultrasound combined with shear wave elastography) and correlation with biopsy outcome and to correlate standard 12 core prostate biopsies with targeted biopsies based on abnormalities identified at DWMRI. [ Time Frame: 5 years ]
    To determine the incidence of abnormal imaging at MRI in correlation with biopsy outcome.

  4. The association of biological sample biomarker profiles with prostate biopsy result. [ Time Frame: 5 years ]
    To identify biomarkers from biological samples and determine their association with prostate biopsy result.

  5. The association of quantitative imaging biomarkers with prostate biopsy result [ Time Frame: 5 years ]
    To identify imaging biomarkers and determine their association with prostate biopsy result.


Biospecimen Retention:   Samples With DNA
Serum, plasma, urine, DNA, RNA


Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
350 men in each cohort
Criteria

Inclusion Criteria:

Men with either:

  1. A positive family history of PrCa defined as:

    • Men with a first degree relative (or second degree if through female line) with histologically or death certificate proven PrCa diagnosed at <70 years
    • Men with two relatives on the same side of the family with histologically or death certificate proven PrCa where at least one is diagnosed at <70 years
    • Men with three relatives on the same side of the family with histologically or death certificate proven PrCa diagnosed at any age
  2. Of African or Caribbean ancestry defined as:

Both parents and all 4 grandparents from that origin

  • Age 40- 69 years
  • WHO performance status 02 (see Appendix A)
  • Absence of any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow up schedule.

Exclusion Criteria:

  • Previous cancer with a life expectancy of less than five years.
  • Previous PrCa
  • Negative biopsy within one year before recruitment
  • Comorbidities making prostate biopsy risk unacceptable (Warfarin or Clopidogrel).
  • Contraindications to having an MRI (pacemakers, aneurysm clips, claustrophobia)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02543905


Contacts
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Contact: Elizabeth K Bancroft, PhD 44 207 808 2136 elizabeth.bancroft@icr.ac.uk
Contact: Eva McGrowder, PhD 44 208 722 4483 eva.mcgrowder@icr.ac.uk

Locations
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United Kingdom
Institute of Cancer Research and Royal Marsden Hospital Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Contact: Rosalind A Eeles, FRCP FRFR    02086613642    rosalind.eeles@icr.ac.uk   
Principal Investigator: Rosalind A Eeles, FRCP FRCR         
Sponsors and Collaborators
Institute of Cancer Research, United Kingdom
Royal Marsden NHS Foundation Trust
University of Cambridge
University of Oxford
Queen Mary University of London
Investigators
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Principal Investigator: Rosalind A Eeles Institute of Cancer Research, United Kingdom
Additional Information:
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Responsible Party: Institute of Cancer Research, United Kingdom
ClinicalTrials.gov Identifier: NCT02543905    
Other Study ID Numbers: CCR4045
First Posted: September 7, 2015    Key Record Dates
Last Update Posted: June 10, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymised data can be applied for via the Data Access Committee

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases