Official Title
A Multi-Center Natural History Study of Precision-Based Genomics in Prostate Cancer
Brief Title
Precision-Based Genomics in Prostate Cancer
Protocol ID
NCT04706663
Lead Sponsor
National Cancer Institute (NCI)
Brief 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.
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 Period
-
Enrollment Count
2,000 participants
Eligibility Criteria
- 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
Filters
Prostate Cancer
RECRUITING
ADULT
OLDER_ADULT