The IMPACT Study - Identification of Men With a Genetic Predisposition to ProstAte Cancer

NCT00261456 | Active Not Recruiting DMC

• 2 other identifiers: 05/MRE07/25CCR2598
• Study Type: observational
• Target: 3,500
• Locations: 1 country
• Sites: 1

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 BRCA1/2. 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.

Conditions

Prostate Cancer; BRCA Mutation; Mismatch Repair Gene Mutation; Genetic Predisposition to Disease

Keywords

Prostate cancer; BRCA1; BRCA2; prostate screening; PSA; prostate biopsy; Lynch Syndrome; Mismatch Repair Genes; MLH1; MSH2; MSH6

Outcome Measures

Primary Outcomes (2)

• Primary Endpoint (BRCA)

  To determine the yearly incidence of screen-detected prostate cancer in BRCA1 and BRCA2 mutation carriers compared with the control population (predictive test negative for a known familial BRCA1/2 gene mutation). "

  Through study completion, a minimum of 10 years follow up in participants.

• Primary Endpoint (Mismatch Repair/Lynch Cohort)

  To determine the yearly incidence of screen-detected prostate cancer in mismatch repair gene mutation carriers compared with the control population (predictive test negative for a known familial MMR gene mutation).

  Through study completion, a minimum of 10 years follow up in participants.

Secondary Outcomes (4)

• PSA threshold for prostate cancer detection

  Through study completion, a minimum of 10 years follow up in participants.

• Positive Predictive value of PSA level for prostate cancer detection

  Through study completion, a minimum of 10 years follow up in participants.

• Cancer Pathology (BRCA)

  Through study completion, a minimum of 10 years follow up in participants.

• Cancer Pathology (Mismatch Repair/Lynch Cohort)

  Through study completion, a minimum of 10 years follow up in participants.

Study Arms (4)

BRCA1/2 carriers

Carriers of a BRCA1 or BRCA2 mutation.

Diagnostic Test: PSA test; Procedure: Prostate Biopsy

BRCA1/2 non Carriers

Do not carry a mutation in either the BRCA1 or 2 genes that has been found in other members of the family.

Diagnostic Test: PSA test; Procedure: Prostate Biopsy

Mismatch Repair gene mutation carriers

Carriers of a MSH2, MSH6 or MLH1 mutation.

Diagnostic Test: PSA test; Procedure: Prostate Biopsy

Mismatch Repair gene mutation non-carriers

Do not carry a mutation in either the MLH1, MSH2 or MSH6 genes that has been found in other members of the family.

Diagnostic Test: PSA test; Procedure: Prostate Biopsy

Interventions

PSA test DIAGNOSTIC_TEST

Patients tested for their level of Prostate Specific Antigen.

BRCA1/2 carriers; BRCA1/2 non Carriers; Mismatch Repair gene mutation carriers; Mismatch Repair gene mutation non-carriers

Prostate Biopsy PROCEDURE

A Prostate biopsy is given as an option to the patient if their PSA level is raised or at the end of 5 years screening.

BRCA1/2 carriers; BRCA1/2 non Carriers; Mismatch Repair gene mutation carriers; Mismatch Repair gene mutation non-carriers

Eligibility Criteria

• Age: 40 Years - 69 Years
• Gender Eligibility Details: Person must have a prostate.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Any patient that meets the eligibility criteria and maybe attending a genetics clinic at a number of international centres that have gone through ethical approval.

You may qualify if:

• Male carriers of a known pathogenic BRCA1/2 or Mismatch Repair gene mutations (MSH2, MSH6, MLH1) or men testing negative for a known BRCA1/2/ Mismatch repair mutation (MSH2, MSH6, MLH1) in their family
• Aged between 40-69 years old
• WHO performance status 0-2
• No previous history of prostate cancer
• No previous prostate biopsy for raised PSA
• Absence of any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow-up schedule
• Fully informed, written consent according to ICH/EU GCP and national/local regulations before subject registration.

You may not qualify if:

• Previous cancer with terminal prognosis of less than 5 years
• Previous prostate cancer

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Cancer Research UK: collaborator
• Royal Marsden NHS Foundation Trust: collaborator
• Ronald and Rita McAulay Foundation: collaborator
• BRCA Research and Cure Alliance: collaborator

Study Sites (1)

Cancer Genetics Unit, Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Related Publications (14)

• Tischkowitz M, Eeles R; IMPACT study: Identification of Men with genetic predisposition to Prostate Cancer and its Clinical Treatment collaborators. Mutations in BRCA1 and BRCA2 and predisposition to prostate cancer. Lancet. 2003 Jul 5;362(9377):80; author reply 80. doi: 10.1016/S0140-6736(03)13823-8. No abstract available.

  PMID: 12853213 BACKGROUND

• Cremers RG, Eeles RA, Bancroft EK, Ringelberg-Borsboom J, Vasen HF, Van Asperen CJ; IMPACT Steering Committee; Schalken JA, Verhaegh GW, Kiemeney LA. The role of the prostate cancer gene 3 urine test in addition to serum prostate-specific antigen level in prostate cancer screening among breast cancer, early-onset gene mutation carriers. Urol Oncol. 2015 May;33(5):202.e19-28. doi: 10.1016/j.urolonc.2015.01.018. Epub 2015 Mar 5.

  PMID: 25746941 BACKGROUND

• Killick E, Morgan R, Launchbury F, Bancroft E, Page E, Castro E, Kote-Jarai Z, Aprikian A, Blanco I, Clowes V, Domchek S, Douglas F, Eccles D, Evans DG, Harris M, Kirk J, Lam J, Lindeman G, Mitchell G, Pachter N, Selkirk C, Tucker K, Zgajnar J, Eeles R, Pandha H. Role of Engrailed-2 (EN2) as a prostate cancer detection biomarker in genetically high risk men. Sci Rep. 2013;3:2059. doi: 10.1038/srep02059.

  PMID: 23792811 BACKGROUND

• Whitaker HC, Kote-Jarai Z, Ross-Adams H, Warren AY, Burge J, George A, Bancroft E, Jhavar S, Leongamornlert D, Tymrakiewicz M, Saunders E, Page E, Mitra A, Mitchell G, Lindeman GJ, Evans DG, Blanco I, Mercer C, Rubinstein WS, Clowes V, Douglas F, Hodgson S, Walker L, Donaldson A, Izatt L, Dorkins H, Male A, Tucker K, Stapleton A, Lam J, Kirk J, Lilja H, Easton D; IMPACT Study Steering Committee; IMPACT Study Collaborators; UK GPCS Collaborators; Cooper C, Eeles R, Neal DE. The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine. PLoS One. 2010 Oct 13;5(10):e13363. doi: 10.1371/journal.pone.0013363.

  PMID: 20967219 BACKGROUND

• Mikropoulos C, Selkirk CGH, Saya S, Bancroft E, Vertosick E, Dadaev T, Brendler C, Page E, Dias A, Evans DG, Rothwell J, Maehle L, Axcrona K, Richardson K, Eccles D, Jensen T, Osther PJ, van Asperen CJ, Vasen H, Kiemeney LA, Ringelberg J, Cybulski C, Wokolorczyk D, Hart R, Glover W, Lam J, Taylor L, Salinas M, Feliubadalo L, Oldenburg R, Cremers R, Verhaegh G, van Zelst-Stams WA, Oosterwijk JC, Cook J, Rosario DJ, Buys SS, Conner T, Domchek S, Powers J, Ausems MG, Teixeira MR, Maia S, Izatt L, Schmutzler R, Rhiem K, Foulkes WD, Boshari T, Davidson R, Ruijs M, Helderman-van den Enden AT, Andrews L, Walker L, Snape K, Henderson A, Jobson I, Lindeman GJ, Liljegren A, Harris M, Adank MA, Kirk J, Taylor A, Susman R, Chen-Shtoyerman R, Pachter N, Spigelman A, Side L, Zgajnar J, Mora J, Brewer C, Gadea N, Brady AF, Gallagher D, van Os T, Donaldson A, Stefansdottir V, Barwell J, James PA, Murphy D, Friedman E, Nicolai N, Greenhalgh L, Obeid E, Murthy V, Copakova L, McGrath J, Teo SH, Strom S, Kast K, Leongamornlert DA, Chamberlain A, Pope J, Newlin AC, Aaronson N, Ardern-Jones A, Bangma C, Castro E, Dearnaley D, Eyfjord J, Falconer A, Foster CS, Gronberg H, Hamdy FC, Johannsson O, Khoo V, Lubinski J, Grindedal EM, McKinley J, Shackleton K, Mitra AV, Moynihan C, Rennert G, Suri M, Tricker K; IMPACT study collaborators; Moss S, Kote-Jarai Z, Vickers A, Lilja H, Helfand BT, Eeles RA. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition. Br J Cancer. 2018 Jan;118(2):266-276. doi: 10.1038/bjc.2017.429. Epub 2018 Jan 4.

  PMID: 29301143 BACKGROUND

• Moynihan C, Bancroft EK, Mitra A, Ardern-Jones A, Castro E, Page EC, Eeles RA. Ambiguity in a masculine world: Being a BRCA1/2 mutation carrier and a man with prostate cancer. Psychooncology. 2017 Nov;26(11):1987-1993. doi: 10.1002/pon.4530. Epub 2017 Sep 18.

  PMID: 28812325 BACKGROUND

• Mitra AV, Bancroft EK, Barbachano Y, Page EC, Foster CS, Jameson C, Mitchell G, Lindeman GJ, Stapleton A, Suthers G, Evans DG, Cruger D, Blanco I, Mercer C, Kirk J, Maehle L, Hodgson S, Walker L, Izatt L, Douglas F, Tucker K, Dorkins H, Clowes V, Male A, Donaldson A, Brewer C, Doherty R, Bulman B, Osther PJ, Salinas M, Eccles D, Axcrona K, Jobson I, Newcombe B, Cybulski C, Rubinstein WS, Buys S, Townshend S, Friedman E, Domchek S, Ramon Y Cajal T, Spigelman A, Teo SH, Nicolai N, Aaronson N, Ardern-Jones A, Bangma C, Dearnaley D, Eyfjord J, Falconer A, Gronberg H, Hamdy F, Johannsson O, Khoo V, Kote-Jarai Z, Lilja H, Lubinski J, Melia J, Moynihan C, Peock S, Rennert G, Schroder F, Sibley P, Suri M, Wilson P, Bignon YJ, Strom S, Tischkowitz M, Liljegren A, Ilencikova D, Abele A, Kyriacou K, van Asperen C, Kiemeney L; IMPACT Study Collaborators; Easton DF, Eeles RA. Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study. BJU Int. 2011 Jan;107(1):28-39. doi: 10.1111/j.1464-410X.2010.09648.x. Epub 2010 Sep 14.

  PMID: 20840664 RESULT

• Bancroft EK, Page EC, Castro E, Lilja H, Vickers A, Sjoberg D, Assel M, Foster CS, Mitchell G, Drew K, Maehle L, Axcrona K, Evans DG, Bulman B, Eccles D, McBride D, van Asperen C, Vasen H, Kiemeney LA, Ringelberg J, Cybulski C, Wokolorczyk D, Selkirk C, Hulick PJ, Bojesen A, Skytte AB, Lam J, Taylor L, Oldenburg R, Cremers R, Verhaegh G, van Zelst-Stams WA, Oosterwijk JC, Blanco I, Salinas M, Cook J, Rosario DJ, Buys S, Conner T, Ausems MG, Ong KR, Hoffman J, Domchek S, Powers J, Teixeira MR, Maia S, Foulkes WD, Taherian N, Ruijs M, Helderman-van den Enden AT, Izatt L, Davidson R, Adank MA, Walker L, Schmutzler R, Tucker K, Kirk J, Hodgson S, Harris M, Douglas F, Lindeman GJ, Zgajnar J, Tischkowitz M, Clowes VE, Susman R, Ramon y Cajal T, Patcher N, Gadea N, Spigelman A, van Os T, Liljegren A, Side L, Brewer C, Brady AF, Donaldson A, Stefansdottir V, Friedman E, Chen-Shtoyerman R, Amor DJ, Copakova L, Barwell J, Giri VN, Murthy V, Nicolai N, Teo SH, Greenhalgh L, Strom S, Henderson A, McGrath J, Gallagher D, Aaronson N, Ardern-Jones A, Bangma C, Dearnaley D, Costello P, Eyfjord J, Rothwell J, Falconer A, Gronberg H, Hamdy FC, Johannsson O, Khoo V, Kote-Jarai Z, Lubinski J, Axcrona U, Melia J, McKinley J, Mitra AV, Moynihan C, Rennert G, Suri M, Wilson P, Killick E; IMPACT Collaborators; Moss S, Eeles RA. Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study. Eur Urol. 2014 Sep;66(3):489-99. doi: 10.1016/j.eururo.2014.01.003. Epub 2014 Jan 15.

  PMID: 24484606 RESULT

• Page EC, Bancroft EK, Brook MN, Assel M, Hassan Al Battat M, Thomas S, Taylor N, Chamberlain A, Pope J, Raghallaigh HN, Evans DG, Rothwell J, Maehle L, Grindedal EM, James P, Mascarenhas L, McKinley J, Side L, Thomas T, van Asperen C, Vasen H, Kiemeney LA, Ringelberg J, Jensen TD, Osther PJS, Helfand BT, Genova E, Oldenburg RA, Cybulski C, Wokolorczyk D, Ong KR, Huber C, Lam J, Taylor L, Salinas M, Feliubadalo L, Oosterwijk JC, van Zelst-Stams W, Cook J, Rosario DJ, Domchek S, Powers J, Buys S, O'Toole K, Ausems MGEM, Schmutzler RK, Rhiem K, Izatt L, Tripathi V, Teixeira MR, Cardoso M, Foulkes WD, Aprikian A, van Randeraad H, Davidson R, Longmuir M, Ruijs MWG, Helderman van den Enden ATJM, Adank M, Williams R, Andrews L, Murphy DG, Halliday D, Walker L, Liljegren A, Carlsson S, Azzabi A, Jobson I, Morton C, Shackleton K, Snape K, Hanson H, Harris M, Tischkowitz M, Taylor A, Kirk J, Susman R, Chen-Shtoyerman R, Spigelman A, Pachter N, Ahmed M, Ramon Y Cajal T, Zgajnar J, Brewer C, Gadea N, Brady AF, van Os T, Gallagher D, Johannsson O, Donaldson A, Barwell J, Nicolai N, Friedman E, Obeid E, Greenhalgh L, Murthy V, Copakova L, Saya S, McGrath J, Cooke P, Ronlund K, Richardson K, Henderson A, Teo SH, Arun B, Kast K, Dias A, Aaronson NK, Ardern-Jones A, Bangma CH, Castro E, Dearnaley D, Eccles DM, Tricker K, Eyfjord J, Falconer A, Foster C, Gronberg H, Hamdy FC, Stefansdottir V, Khoo V, Lindeman GJ, Lubinski J, Axcrona K, Mikropoulos C, Mitra A, Moynihan C, Rennert G, Suri M, Wilson P, Dudderidge T; IMPACT Study Collaborators; Offman J, Kote-Jarai Z, Vickers A, Lilja H, Eeles RA. Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers. Eur Urol. 2019 Dec;76(6):831-842. doi: 10.1016/j.eururo.2019.08.019. Epub 2019 Sep 16.

  PMID: 31537406 RESULT

• Dias A, Brook MN, Bancroft EK, Page EC, Chamberlain A, Saya S, Amin J, Mikropoulos C, Taylor N, Myhill K, Thomas S, Saunders E, Dadaev T, Leongamornlert D, Dyrso Jensen T, Evans DG, Cybulski C, Liljegren A, Teo SH, Side L; IMPACT study collaborators and Steering Committee; Kote-Jarai Z, Eeles RA. Serum testosterone and prostate cancer in men with germline BRCA1/2 pathogenic variants. BJUI Compass. 2023 Jan 9;4(3):361-373. doi: 10.1002/bco2.156. eCollection 2023 May.

  PMID: 37025481 RESULT

• Bancroft EK, Page EC, Brook MN, Thomas S, Taylor N, Pope J, McHugh J, Jones AB, Karlsson Q, Merson S, Ong KR, Hoffman J, Huber C, Maehle L, Grindedal EM, Stormorken A, Evans DG, Rothwell J, Lalloo F, Brady AF, Bartlett M, Snape K, Hanson H, James P, McKinley J, Mascarenhas L, Syngal S, Ukaegbu C, Side L, Thomas T, Barwell J, Teixeira MR, Izatt L, Suri M, Macrae FA, Poplawski N, Chen-Shtoyerman R, Ahmed M, Musgrave H, Nicolai N, Greenhalgh L, Brewer C, Pachter N, Spigelman AD, Azzabi A, Helfand BT, Halliday D, Buys S, Ramon Y Cajal T, Donaldson A, Cooney KA, Harris M, McGrath J, Davidson R, Taylor A, Cooke P, Myhill K, Hogben M, Aaronson NK, Ardern-Jones A, Bangma CH, Castro E, Dearnaley D, Dias A, Dudderidge T, Eccles DM, Green K, Eyfjord J, Falconer A, Foster CS, Gronberg H, Hamdy FC, Johannsson O, Khoo V, Lilja H, Lindeman GJ, Lubinski J, Axcrona K, Mikropoulos C, Mitra AV, Moynihan C, Ni Raghallaigh H, Rennert G, Collier R; IMPACT Study Collaborators; Offman J, Kote-Jarai Z, Eeles RA. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study. Lancet Oncol. 2021 Nov;22(11):1618-1631. doi: 10.1016/S1470-2045(21)00522-2. Epub 2021 Oct 19.

  PMID: 34678156 RESULT

• Bancroft EK, Saya S, Page EC, Myhill K, Thomas S, Pope J, Chamberlain A, Hart R, Glover W, Cook J, Rosario DJ, Helfand BT, Hutten Selkirk C, Davidson R, Longmuir M, Eccles DM, Gadea N, Brewer C, Barwell J, Salinas M, Greenhalgh L, Tischkowitz M, Henderson A, Evans DG, Buys SS; IMPACT Study Steering Committee; IMPACT Collaborators; Eeles RA, Aaronson NK. Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations. BJU Int. 2019 Feb;123(2):284-292. doi: 10.1111/bju.14412. Epub 2018 Jun 22.

  PMID: 29802810 RESULT

• Bancroft EK, Page EC, Brook MN, Pope J, Thomas S, Myhill K, Helfand BT, Talaty P, Ong KR, Douglas E, Cook J, Rosario DJ, Salinas M, Buys SS, Anson J, Davidson R, Longmuir M, Side L, Eccles DM, Tischkowitz M, Taylor A, Cruellas M, Ballestero EP, Cleaver R, Varughese M, Barwell J, LeButt M, Greenhalgh L, Hart R, Azzabi A, Jobson I, Cogley L, Evans DG, Rothwell J, Taylor N, Hogben M, Saya S; IMPACT Study Steering Committee; IMPACT Collaborators; Eeles RA, Aaronson NK. The psychosocial impact of prostate cancer screening for BRCA1 and BRCA2 carriers. BJU Int. 2024 Sep;134(3):484-500. doi: 10.1111/bju.16432. Epub 2024 Jun 5.

  PMID: 38839570 RESULT

• Das S, Salami SS, Spratt DE, Kaffenberger SD, Jacobs MF, Morgan TM. Bringing Prostate Cancer Germline Genetics into Clinical Practice. J Urol. 2019 Aug;202(2):223-230. doi: 10.1097/JU.0000000000000137. Epub 2019 Jul 8.

  PMID: 30730411 DERIVED

Related Links

• The IMPACT study website
• UK information point for eligible men

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, Serum, Plasma, Urine, Prostate tissue.

MeSH Terms

Conditions

Prostatic Neoplasms; Genetic Predisposition to Disease; Colorectal Neoplasms, Hereditary Nonpolyposis

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Rosalind A Eeles, FRCP FRCR

  Institute of Cancer Research and Royal Marsden Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2005
• First Posted: December 5, 2005
• Study Start: March 1, 2005
• Primary Completion (Estimated): February 28, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)