Prostate Cancer Genetic Risk Evaluation and Screening Study

Clinicaltrials.gov ID: NCT05129605
db-list-check Status RECRUITING
b-loader Phase
b-people Age 35 - 74 Years
b-bullseye-arrow Enrollments 400

Conditions

Prostatic Neoplasm, Prostate Cancer, BRCA2 Mutation, BRCA1 Mutation, ATM Gene Mutation, MMR Mutation, Lynch Syndrome, Genetic Predisposition to Disease

Summary

This study aims to define the natural history of men at high genetic risk for prostate cancer on the basis of specific germline genetic mutations, family history, or Black/African ancestry and evaluate the utility of prostate MRI as a screening tool. The hypothesis is that this targeted population of men are at elevated risk of developing prostate cancer compared to the general population, and enhanced screening with MRI will enable early detection and diagnosis of potentially aggressive prostate cancer, characterization of the penetrance of specific mutations, and potentially identify new genetic risk mutations.

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 men harboring specific genetic variants or a positive family history have been associated with an increased risk of developing prostate cancer. Men with specific genetic variants, such as pathogenic BRCA2 mutations, are at particularly greater risk of developing aggressive forms of prostate cancer and thus warrant undergoing careful screening for prostate cancer. However, the penetrance of many mutations in prostate cancer risk genes is unknown, and some men have no identifiable mutations in known risk genes despite a strong family history of prostate cancer. Prospectively collected clinical data along with biospecimens from unaffected individuals at high genetic risk for developing prostate cancer will advance the understanding of how specific mutations contribute to the development of prostate cancer and how these prostate cancers might be best detected. The purpose of this study is to prospectively screen men at high risk genetic risk for prostate cancer by prostate exam, PSA, and prostate MRI to characterize the penetrance and cancer-related outcomes of specific mutations, identify potentially novel genetic risk mutations and/or markers for early detection.

Locations

1 location Found with status Recruiting

Status

  • RECRUITING

Central Contacts

Principal Investigator

  • Keyan Salari, MD, PhD

Eligibility Criteria

Inclusion Criteria:

* Men 35-74 years old
* No known diagnosis of prostate cancer
* Life expectancy >10 years
* Meet cohort A, B, or C criteria
* Cohort A: Documented pathogenic or likely pathogenic germline genetic mutation in a prostate cancer risk gene from a CLIA-certified laboratory (ATM, ATR, BRCA1, BRCA2, BRIP1, CHEK2, EPCAM, FANCA, GEN1, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51C, RAD51D, TP53)
* Cohort B: A strong family history suggestive of high genetic risk for prostate cancer with negative clinical genetic testing
* Cohort C: Individuals who self-identify as Black American or Black Caribbean with both parents and all four grandparents of Black/African ancestry

Exclusion Criteria:

* Prior diagnosis or treatment of prostate cancer
* Inability to undergo prostate MRI
* Inability to receive MRI contrast agent

Study Plan

Cohort A

Documented germline known pathogenic or likely pathogenic mutation in a prostate cancer related risk gene

  • DIAGNOSTIC_TEST:

    Prostate cancer screening

    Description:

    Physical exam (digital rectal exam), prostate-specific antigen (PSA) and PSA derivatives, and multiparametric MRI of the prostate

Cohort B

Family history suggestive of high genetic risk for prostate cancer with clinical genetic testing negative for known pathogenic or likely pathogenic mutations in prostate cancer-related risk genes

  • DIAGNOSTIC_TEST:

    Prostate cancer screening

    Description:

    Physical exam (digital rectal exam), prostate-specific antigen (PSA) and PSA derivatives, and multiparametric MRI of the prostate

Cohort C

Individuals who self-identify as Black American or Black Caribbean with both parents and all four grandparents of Black/African ancestry

  • DIAGNOSTIC_TEST:

    Prostate cancer screening

    Description:

    Physical exam (digital rectal exam), prostate-specific antigen (PSA) and PSA derivatives, and multiparametric MRI of the prostate

Outcome Measures

Primary Outcome Measures

Diagnosis of prostate cancer

Time Frame: From date of enrollment until date of diagnosis of prostate cancer or age of 75 reached, which ever came first

Secondary Outcome Measures

Positive predictive value of multiparametric MRI for detection of prostate cancer

Time Frame: From date of enrollment until date of diagnosis of prostate cancer or age of 75 reached, which ever came first

Timeline

  • Last Updated
    October 9, 2024
  • Start Date
    November 22, 2021
  • Today
    January 16, 2025
  • Completion Date ( Estimated )
    December 1, 2040

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