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Men at High Genetic Risk for Prostate Cancer

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ClinicalTrials.gov Identifier: NCT03805919
Recruitment Status : Recruiting
First Posted : January 16, 2019
Last Update Posted : January 26, 2023
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


Research studies have shown that genetic changes and family history may increase a man s risk for prostate cancer. Researchers want to follow the prostate health of men who have specific genetic changes associated with prostate cancer to help them learn more about which men are at higher risk for prostate cancer.


To study men with specific genetic changes and determine who is at higher risk for getting prostate cancer. To study if certain genetic changes and family history can be used to help prevent or treat prostate cancer.


Persons assigned male at birth ages 30-75 who have one or more specific genetic changes but without prostate cancer.


  • This study does not perform genetic testing. All participants must have documented genetic changes and able to provide a copy of the report.
  • Before enrollment, participants will provide a copy of documented genetic changes and go through a telephone interview to determine eligibility for the study.
  • On enrollment, participants will have medical and family history review, medication review, physical exam, blood collection for clinical and research testing, and MRI (magnetic resonance imaging) of the prostate.
  • Every year, participants will repeat the physical exam, medical history, family history, medication review, routine blood tests, including PSA and testosterone.
  • Every 2 years, participants will repeat all the above plus prostate MRI and blood tests for research.
  • If, at any time, the physical exam, blood tests or MRI are abnormal, participants may be asked to do a biopsy.
  • If the biopsy results in prostate cancer, participants will be given counseling on next steps, general treatment recommendations, and then followed with a phone call each year.
  • Participants may ask to speak with a genetic counselor.

Condition or disease
Prostatic Neoplasms

Detailed Description:


Prostate cancer is the most common malignancy and the second leading cause of cancer-related deaths in American men.

Prostate cancer has substantial inherited predisposition and certain genetic variants that are associated with an increased risk of prostate cancer.

An evolving approach to prostate cancer screening is to target populations at risk of developing prostate cancer based on their genetic predisposition.


To follow the natural history of men with known germline variants or likely pathogenic variants in genes that put them at risk for developing prostate cancer.


Persons assigned male at birth who are between ages 30-75 years old.

Documented germline pathogenic or likely pathogenic variants in prostate cancer-related risk gene: BRCA 1 and 2, DNA Mismatch Repair (MMR) genes associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM), HOXB13, ATM, NBN, TP53, CHEK2, PALB2, RAD51C, RAD51D, BRIP1, or FANC (FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, and FANCM).

Must be able and willing to provide informed consent.


Up to 500 subjects will be enrolled.

Participants will undergo sampling of blood for prostate-specific antigen. Based on these results and age, participants will be considered for biopsy and/or continued monitoring if feasible upon clinical discretion.

Participants will undergo a baseline MRI evaluation with follow-up scans every 2 years as clinically indicated.

Following initial evaluation, participants will be followed as clinically indicated, usually at 12 month intervals, to determine their PSA level, prostate cancer treatment (if relevant) and/or disease/survival status until death.

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Study Type : Observational
Estimated Enrollment : 500 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Natural History Study of Men at High Genetic Risk for Prostate Cancer
Actual Study Start Date : March 27, 2019
Estimated Primary Completion Date : January 1, 2029
Estimated Study Completion Date : January 1, 2039

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Cohort 1
Participants with germline pathogenic or likely pathogenic variants in prostate cancer-related risk genes

Primary Outcome Measures :
  1. Natural history of high genetic risk for prostate cancer [ Time Frame: one year ]
    To follow the natural history of men with known germline variants or likely pathogenic variants in genes that put them at high risk for developing prostate cancer

Secondary Outcome Measures :
  1. mpMRI feasibility [ Time Frame: baseline and every two years until death or when criteria for removal from study is met ]
    test the feasibility and accuracy of multi parametric magnetic resonance imaging (mpMRI) for the localization and detection of local prostate cancer

  2. role of mpMRI [ Time Frame: baseline and every two years until death or when criteria for removal from study is met ]
    role of mpMRI in monitoring participants on active surveillance and as a follow up tool for monitoring local disease progression

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Persons assigned male at birth with a documented germline variant in prostate cancer risk-related gene from a CLIA certified laboratory
  • Inclusion Criteria:
  • Persons assigned male at birth between the ages of 30-75 years.
  • Documented germline variant (i.e. pathogenic/likely pathogenic variant) in prostate cancer risk-related gene from a CLIA certified laboratory: BRCA1 and BRCA2, MMR genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) associated with Lynch syndrome, as well as HOXB13, ATM, NBN, TP53, CHEK2, PALB2, RAD51C, RAD51D, BRIP1, or FANC (FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, and FANCM).
  • Prognosis of >5 years survival if affected by another cancer
  • Ability of subject to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Prior diagnosis or treatment for prostate cancer
  • Known contraindication to MRI:

    • Participants unable to fit through MRI scanner (radiologist discretion)
    • Allergy to MR contrast agent
    • Participants with pacemakers, cerebral aneurysm clips, shrapnel injury, or implantable electronic device
  • Active concomitant medical or psychological illnesses that may increase the risk to the subject or inability to obtain informed consent, at the discretion of the principal investigator.

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): NCT03805919

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Contact: Anna C Couvillon, C.R.N.P. (240) 858-3148 couvilla@mail.nih.gov
Contact: Fatima H Karzai, M.D. (301) 480-7174 fatima.karzai@nih.gov

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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY dial 711    ccopr@nih.gov   
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Fatima H Karzai, M.D. National Cancer Institute (NCI)
Additional Information:
Al Olama AA, Kote-Jarai Z, Berndt SI, Conti DV, Schumacher F, Han Y, Benlloch S, Hazelett DJ, Wang Z, Saunders E, Leongamornlert D, Lindstrom S, Jugurnauth-Little S, Dadaev T, Tymrakiewicz M, Stram DO, Rand K, Wan P, Stram A, Sheng X, Pooler LC, Park K, Xia L, Tyrer J, Kolonel LN, Le Marchand L, Hoover RN, Machiela MJ, Yeager M, Burdette L, Chung CC, Hutchinson A, Yu K, Goh C, Ahmed M, Govindasami K, Guy M, Tammela TL, Auvinen A, Wahlfors T, Schleutker J, Visakorpi T, Leinonen KA, Xu J, Aly M, Donovan J, Travis RC, Key TJ, Siddiq A, Canzian F, Khaw KT, Takahashi A, Kubo M, Pharoah P, Pashayan N, Weischer M, Nordestgaard BG, Nielsen SF, Klarskov P, Roder MA, Iversen P, Thibodeau SN, McDonnell SK, Schaid DJ, Stanford JL, Kolb S, Holt S, Knudsen B, Coll AH, Gapstur SM, Diver WR, Stevens VL, Maier C, Luedeke M, Herkommer K, Rinckleb AE, Strom SS, Pettaway C, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, Cannon-Albright L, Cybulski C, Wokolorczyk D, Kluzniak W, Park J, Sellers T, Lin HY, Isaacs WB, Partin AW, Brenner H, Dieffenbach AK, Stegmaier C, Chen C, Giovannucci EL, Ma J, Stampfer M, Penney KL, Mucci L, John EM, Ingles SA, Kittles RA, Murphy AB, Pandha H, Michael A, Kierzek AM, Blot W, Signorello LB, Zheng W, Albanes D, Virtamo J, Weinstein S, Nemesure B, Carpten J, Leske C, Wu SY, Hennis A, Kibel AS, Rybicki BA, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Zheng SL, Batra J, Clements J, Spurdle A, Teixeira MR, Paulo P, Maia S, Slavov C, Kaneva R, Mitev V, Witte JS, Casey G, Gillanders EM, Seminara D, Riboli E, Hamdy FC, Coetzee GA, Li Q, Freedman ML, Hunter DJ, Muir K, Gronberg H, Neal DE, Southey M, Giles GG, Severi G; Breast and Prostate Cancer Cohort Consortium (BPC3); PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium; COGS (Collaborative Oncological Gene-environment Study) Consortium; GAME-ON/ELLIPSE Consortium; Cook MB, Nakagawa H, Wiklund F, Kraft P, Chanock SJ, Henderson BE, Easton DF, Eeles RA, Haiman CA. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet. 2014 Oct;46(10):1103-9. doi: 10.1038/ng.3094. Epub 2014 Sep 14.
Giri VN, Knudsen KE, Kelly WK, Abida W, Andriole GL, Bangma CH, Bekelman JE, Benson MC, Blanco A, Burnett A, Catalona WJ, Cooney KA, Cooperberg M, Crawford DE, Den RB, Dicker AP, Eggener S, Fleshner N, Freedman ML, Hamdy FC, Hoffman-Censits J, Hurwitz MD, Hyatt C, Isaacs WB, Kane CJ, Kantoff P, Karnes RJ, Karsh LI, Klein EA, Lin DW, Loughlin KR, Lu-Yao G, Malkowicz SB, Mann MJ, Mark JR, McCue PA, Miner MM, Morgan T, Moul JW, Myers RE, Nielsen SM, Obeid E, Pavlovich CP, Peiper SC, Penson DF, Petrylak D, Pettaway CA, Pilarski R, Pinto PA, Poage W, Raj GV, Rebbeck TR, Robson ME, Rosenberg MT, Sandler H, Sartor O, Schaeffer E, Schwartz GF, Shahin MS, Shore ND, Shuch B, Soule HR, Tomlins SA, Trabulsi EJ, Uzzo R, Vander Griend DJ, Walsh PC, Weil CJ, Wender R, Gomella LG. Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017. J Clin Oncol. 2018 Feb 1;36(4):414-424. doi: 10.1200/JCO.2017.74.1173. Epub 2017 Dec 13.

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03805919    
Other Study ID Numbers: 190040
First Posted: January 16, 2019    Key Record Dates
Last Update Posted: January 26, 2023
Last Verified: January 23, 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: . All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@ In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Clinical data available during the study and indefinitely.@@@@@@ Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@ Genomic data are made available via dbGaP through requests to the data custodians.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
MMR genes
Lynch Syndrome
Natural History
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases