Precision-Based Genomics in Prostate Cancer

NCT ID: NCT04706663

Last Updated: 2026-01-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

2000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-09-14

Study Completion Date

2027-06-30

Brief Summary

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Background:

Prostate cancer is the most common cancer and the second leading cause of death in males in the United States. Researchers want to find additional gene mutations that may increase a man s risk for prostate cancer and may affect how aggressive the disease is.

Objective:

To look at gene mutations in men with prostate cancer as well as the course of their disease to better understand how gene mutations relate to the way the cancer progresses and responds to treatment.

Eligibility:

Adult males 18 and older with prostate cancer who have at least one of the gene mutations researchers want to study and/or have been treated for their cancer and have had complete elimination of their cancer or stable disease for a long time.

Design:

Participants will be screened with a review of their medical records. Their gene test results will be reviewed, if available. They will be asked questions over the phone or in person.

Participants do not need to visit the NIH for this study. But if they visit NIH for another study, their data and test results will be collected. They may give blood and urine samples. They may give leftover tumor samples. These samples will be used to study their genes.

Participants who do not come to NIH on regular basis will be contacted every 6 months by phone or e-mail. They will be asked questions about their health. Data from their medical records will be collected.

Participants will have testosterone and prostate-specific antigen (PSA) tests.

Participants may be invited to NIH to give blood samples for research.

Participants on this study will be followed for life.

Detailed Description

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Background:

* Prostate cancer is the most common cancer and the second leading cause of death in males in the United States with an estimated 191,930 new cases and 33,330 deaths in 2020.
* There has been progress in identifying established risk factors for the development of prostate cancer, including genetic predisposition. The study of the molecular genetics of prostate cancer has identified pathogenic variants, such as BRCA1 and BRCA2 (associated with hereditary breast and ovarian cancer syndrome), HOXB13 (associated with hereditary prostate cancer), and DNA mismatch repair (MMR) gene variants (MLH1, MSH2, MSH6, PMS2, and EPCAM) associated with Lynch syndrome.
* While our understanding of molecular genetics continues to grow, there remains a need to identify additional germline and somatic mutations and alterations that may increase an individual s risk to develop prostate cancer and potentially the aggressiveness of the disease. In studying the following alterations in prostate cancer, in both localized and advanced stages, potential expanded molecular findings may lead to actionable therapeutic targets and biomarker development. A better understanding of molecular genetics in a longitudinal study of subjects with prostate cancer may be helpful for the design of future treatment studies, and to develop a better understanding of the natural history of the disease

Objectives:

* To longitudinally evaluate subjects with prostate cancer with known germline and/or somatic variants in PIK3 and/or AKT, PALB2, BRIP1, RAD50, RAD51, RAD54, RB1, SPOP, Wnt/B-catenin pathway, CDK12, and MMR genes: MLH1, MSH2, MSH6, PMS2, and EPCAM to better understand the natural history of the disease.
* To longitudinally evaluate subjects with tumor mutational burden-high (TMB-H) prostate cancer (greater than or equal to 10 mutations/megabase \[mut/Mb\] or blood TMB (bTMB) \[greater than or equal to16 mut/Mb\]).

Eligibility:

* Subjects with histologically confirmed prostate cancer
* Must have known germline and/or somatic variants in PIK3 and/or AKT, PALB2, BRIP1, RAD50, RAD51, RAD54, RB1, SPOP, Wnt/B-catenin pathway, CDK12, and MMR genes: MLH1, MSH2, MSH6, PMS2, and EPCAM and/or TMB-high or be deemed an exceptional responder. NOTE: any platform for genomics testing is acceptable (research or CLIA-certified)
* Age greater than or equal to 18 years old

Design:

* This will be a long-term multi-center study to comprehensively study participants with prostate cancer.
* Participants will provide clinical information (including medical history, clinical tests, imaging studies and reports, surgical pathology reports, genetic test results).
* Since long-term follow-up of individuals with prostate cancer is a major feature of the study, local sites intend to maintain active contact with study subjects for as long as possible. Participants will be followed throughout the course of their illnesses, with particular attention to patterns of disease recurrence and progression, response to therapies and duration of responses.

Conditions

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Prostate Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cohort 1

Subjects with histologically confirmed prostate cancer and genomic testing results

No interventions assigned to this group

Cohort 2

Subjects with histologically confirmed prostate cancer who deemed to be an exceptional responder with or without genomic testing results

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Subjects with histologically confirmed prostate cancer.
* Must have known germline and/or somatic variants in PIK3 and/or AKT, PALB2, BRIP1, RAD50, RAD51, RAD54, RB1, SPOP, Wnt/B-catenin pathway, CDK12, and/or MMR genes: MLH1, MSH2, MSH6, PMS2, and EPCAM and/or TMB-high(\[defined as greater than or equal to 10 mutations/megabase (mut/Mb) and/or bTMB \[greater than or equal to 16 mut/Mb\]. NOTE: any platform for genomics testing is acceptable (research or CLIA-certified)

OR

* be deemed an exceptional responder. NOTE: an exceptional response is defined as achievement of either a) a complete response, or b) a confirmed partial response in a trial or treatment or a response of exceptionally long duration
* Age greater than or equal to 18 years old.
* Ability of subject to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

-None
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fatima H Karzai, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

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University of California San Diego

La Jolla, California, United States

Site Status RECRUITING

University of California San Francisco

San Francisco, California, United States

Site Status RECRUITING

NorthShore University HealthSystem

Evanston, Illinois, United States

Site Status RECRUITING

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Dana Farber Cancer Institute, Boston, MA

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status NOT_YET_RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Mount Sinai Hospital

New York, New York, United States

Site Status NOT_YET_RECRUITING

Weill Cornell Medicine

New York, New York, United States

Site Status NOT_YET_RECRUITING

Oregon Health Sciences University

Portland, Oregon, United States

Site Status NOT_YET_RECRUITING

University of Washington

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Katherine O Lee-Wisdom, R.N.

Role: CONTACT

(240) 858-3525

Fatima H Karzai, M.D.

Role: CONTACT

(301) 480-7174

Facility Contacts

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Suzanna Lee

Role: primary

858-657-7516

Kaitlin Zablotsky

Role: primary

415-502-5775

Michelle Watts

Role: primary

847-570-4193

Fatima Karzai, M.D.

Role: primary

301-480-7174

Dory Freeman

Role: primary

617-632-2389

Arul Chinnaiyan

Role: primary

734-647-8903

Ashley Regazzi

Role: primary

646-888-1359

William Oh

Role: primary

212-241-6756

Cora Sternberg

Role: primary

646-962-2072

Julie Graff

Role: primary

503-494-6594

Thomas Murphy

Role: primary

206-598-0860

Related Links

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Other Identifiers

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000048-C

Identifier Type: -

Identifier Source: secondary_id

10000048

Identifier Type: -

Identifier Source: org_study_id

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