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

Tracking Information

• First Submitted Date: November 2, 2021
• First Posted Date: November 22, 2021
• Last Update Posted Date: March 15, 2023
• Actual Study Start Date: February 12, 2020
• Estimated Primary Completion Date: December 2030 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 9, 2021)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 9, 2021)

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)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prostate Cancer Genetic Risk Evaluation and Screening Study
• Official Title: Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS)
• 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.
• 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 Type: Observational [Patient Registry]
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: 20 Years

Biospecimen

Retention:   Samples With DNA

Description:

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

• 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.

Condition

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

Intervention

Diagnostic Test: Prostate cancer screening

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

Study Groups/Cohorts

• Cohort 1
  Documented germline known pathogenic or likely pathogenic mutation in a prostate cancer related risk gene
  Intervention: Diagnostic Test: Prostate cancer screening
• 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
  Intervention: Diagnostic Test: Prostate cancer screening

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 9, 2021): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2040
• Estimated Primary Completion Date: December 2030 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 35 Years to 74 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05129605
• Other Study ID Numbers: 2020P000081
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Keyan Salari, MD, PhD, Massachusetts General Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Massachusetts General Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Massachusetts General Hospital
• Verification Date: March 2023