Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS)

• ClinicalTrials.gov Identifier: NCT05129605
• Recruitment Status: Recruiting
• First Posted: November 22, 2021
• Last Update Posted: March 15, 2023
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Keyan Salari, MD, PhD, Massachusetts General Hospital

Study Description

Brief 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 or a positive family history 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.

Condition or disease	Intervention/treatment
Prostatic Neoplasm; Prostate Cancer; BRCA2 Mutation; BRCA1 Mutation; ATM Gene Mutation; MMR Mutation; Lynch Syndrome; Genetic Predisposition to Disease	Diagnostic Test: Prostate cancer screening

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.

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 200 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 20 Years
• Official Title: Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS)
• Actual Study Start Date: February 12, 2020
• Estimated Primary Completion Date: December 2030
• Estimated Study Completion Date: December 2040

Groups and Cohorts

Group/Cohort	Intervention/treatment
Cohort 1; Documented germline known pathogenic or likely pathogenic mutation in a prostate cancer related risk gene	Diagnostic Test: Prostate cancer screening; Physical exam (digital rectal exam), prostate-specific antigen (PSA) and PSA derivatives, and multiparametric MRI of the prostate
Cohort 2; 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; Physical exam (digital rectal exam), prostate-specific antigen (PSA) and PSA derivatives, and multiparametric MRI of the prostate

Outcome Measures

Primary Outcome Measures :

1. 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, assessed up to 20 years ]
   Diagnosis of prostate cancer stratified by NCCN clinical risk category incorporating clinical stage, grade, and PSA at diagnosis.

Secondary Outcome Measures :

1. 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, assessed up to 20 years ]
   Positive predictive value of multiparametric prostate MRI for detecting clinically significant prostate cancer in men at high genetic risk for prostate cancer with a positive MRI (PI-RADS score of 3 or higher)

Biospecimen Retention:   Samples With DNA

• Saliva, blood, and urine on all subjects
• Tumor tissue on subjects who develop prostate cancer

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 74 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Men ages 35-74 years old at high genetic risk for prostate cancer on the basis of a specific germline genetic mutation or a strong family history.

Criteria

Inclusion Criteria:

• Men 35-74 years old
• No known diagnosis of prostate cancer
• Life expectancy >10 years
• Meet either cohort 1 or 2 criteria
• Cohort 1: 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 2: A strong family history suggestive of high genetic risk for prostate cancer with negative clinical genetic testing

Exclusion Criteria:

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

Contacts and Locations

Contacts

Contact: Olympia Price; 857-238-3838; oprice@partners.org

Locations

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

• Principal Investigator: Keyan Salari, MD, PhD; Massachusetts General Hospital

More Information

• Responsible Party: Keyan Salari, MD, PhD, Urologic Oncology, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT05129605
• Other Study ID Numbers: 2020P000081
• First Posted: November 22, 2021
• Last Update Posted: March 15, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Keyan Salari, MD, PhD, Massachusetts General Hospital:

BRCA2; BRCA1; Mismatch Repair Deficiency; Lynch Syndrome; HOXB13; Family History of Prostate Cancer

Additional relevant MeSH terms:

Prostatic Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; Genetic Predisposition to Disease; Pathologic Processes; 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; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Metabolic Diseases