Prostate CancerNCT04706663
Precision-Based Genomics in Prostate Cancer
An observational study of Prostate Cancer, run by National Cancer Institute (NCI) at 11 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 120 years, men only
- Conditions the study is for
- Prostate Cancer
- How many people
- 2,000 participants
- Where
- 11 sitesUnited States
- Study dates
- 14 Sep 2021to 30 Jun 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: primary clinical
Who may be able to join
- 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.
Who cannot join
- -None
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
United States11 sites, 11 recruiting
- Not yet recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Arul Chinnaiyan, 734-647-8903, arul@med.umich.edu
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Fatima Karzai, M.D., 301-480-7174, fatima.karzai@nih.gov
- Recruiting
Dana Farber Cancer Institute, Boston, MA
Boston, Massachusetts, 02215
Dory Freeman, 617-632-2389, DoryA_Freeman@DFCI.HARVARD.EDU
- Recruiting
NorthShore University HealthSystem
Evanston, Illinois, 60201
Michelle Watts, 847-570-4193, mwatts@northshore.org
- Recruiting
University of California San Diego
La Jolla, California, 92093
Suzanna Lee, 858-657-7516, suzanna@health.ucsd.edu
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10007
Ashley Regazzi, 646-888-1359, regazzia@mskcc.org
- Not yet recruiting
Mount Sinai Hospital
New York, New York, 10029
William Oh, 212-241-6756, William.Oh@mssm.edu
- Not yet recruiting
Weill Cornell Medicine
New York, New York, 10065
Cora Sternberg, 646-962-2072, cns9006@med.cornell.edu
- Not yet recruiting
Oregon Health Sciences University
Portland, Oregon, 97239
Julie Graff, 503-494-6594, graffj@ohsu.edu
- Recruiting
University of California San Francisco
San Francisco, California, 94143
UCSF Genitourinary, 877-827-3222, GUTrials@ucsf.edu
- Recruiting
University of Washington
Seattle, Washington, 98195
Thomas Murphy, 206-598-0860, tmurphy@fredhutch.org
About this study
Official title: A Multi-Center Natural History Study of Precision-Based Genomics in Prostate Cancer
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.
Read more
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.
Read the detailed description
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
- Prostate Cancer
- Keywords
- germline variants, somatic variants, Genetic Predisposition, Molecular Genetics, Natural History
- Medical subject headings
- Prostatic Neoplasms, Genetic Predisposition to Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Subjects with histologically confirmed prostate cancer and genomic testing results | |
| Cohort 2 | Subjects with histologically confirmed prostate cancer who deemed to be an exceptional responder with or without genomic testing results |
What is being measured
The primary outcome is the main question the study is designed to answer.
natural history of prostate cancer with known germline and/or somatic variants
clinical presentation, patterns of disease progression, therapeutic response, disease recurrence and participant overall survival
Measured: ongoing
natural history of TMB-H prostate cancer
clinical presentation, patterns of disease progression, therapeutic response, disease recurrence and participant overall survival
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2021
- Study start14 Sep 2021
- Primary completion30 Jun 2029 (estimated)
- Study completion30 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Fatima H Karzai, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04706663
- Sponsor's protocol ID
- 10000048
- Other IDs
- 000048-C
- Status last verified
- 13 Oct 2026
- First submitted
- 12 Jan 2021
- Last updated
- 26 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center Natural History Study of Precision-Based Genomics in Prostate Cancer
- ClinicalTrials.gov ID
- NCT04706663
- Acronym / sponsor ID
- 10000048
- Conditions
- Prostate Cancer
- Keywords
- germline variants, somatic variants, Genetic Predisposition, Molecular Genetics, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 14 Sep 2021 (actual)
- Primary completion
- 30 Jun 2029 (estimated)
- Study completion
- 30 Jun 2030 (estimated)
- First posted
- 13 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | – | –Subjects with histologically confirmed prostate cancer and genomic testing results |
| Cohort 2 | – | –Subjects with histologically confirmed prostate cancer who deemed to be an exceptional responder with or without genomic testing results |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- primary clinical
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (1 listed)
- -None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
natural history of prostate cancer with known germline and/or somatic variants
Time frame: ongoing
clinical presentation, patterns of disease progression, therapeutic response, disease recurrence and participant overall survival
natural history of TMB-H prostate cancer
Time frame: ongoing
clinical presentation, patterns of disease progression, therapeutic response, disease recurrence and participant overall survival
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fatima H Karzai, M.D. principal investigator
National Cancer Institute (NCI)
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prostate Cancer, run by National Cancer Institute (NCI) at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Katherine O Lee-Wisdom, R.N. ((240) 858-3525, katherine.lee-wisdom@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
natural history of prostate cancer with known germline and/or somatic variants (time frame: ongoing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.