Clinical trial NCT02053805: Prostate Cancer Screening Among Men With High Risk Genetic Predisposition
Official title: Personalized Prostate Cancer Screening Among Men With High Risk Genetic Predisposition- a Prospective Cohort Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: BRCA1 Syndrome
BRCA2 Syndrome
Lynch Syndrome
Keywords: prostate cancer
BRCA1 Syndrome
BRCA germ-line mutation
Lynch syndrome
BRCA2 Syndrome
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
First posted: 2014-02-04
Enrollment: 200
Sex: MALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: This will be a prospective diagnostic trial of screening for prostate cancer among men with genetic predisposition.

Detailed description: This will be a prospective diagnostic trial of screening for prostate cancer among men with genetic predisposition. The target population is males (40-70 year old) carrying a BRCA1 and/or BRCA2 germ line mutation. They will be identified via our Genetic counseling unit. All men after signing an informed consent will undergo the following tests: PSA, free to total PSA, MRI of prostate and prostate biopsy. The primary endpoint will be to estimate the prevalence, stage and grade of prostate cancer in this population. Additionally, the study aims to estimate the impact of these germ line mutations on benign prostatic hyperplasia. Furthermore, this study aims to create a bio-bank of tissue, urine and serum of this unique cohort for future investigations. Finally, this study will identify an inception cohort for future interventional studies of primary and secondary prevention.

Eligibility criteria: Inclusion Criteria:

* Male carrier of mutation in BRCA 1\\2 or germ-line mutations in the MMR genes (MLH1, MSH2 , MSH6 or PMS2).
* WHO performance status 0-2 (Appendix 2)
* Absence of any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow-up schedule.
* Individuals that cannot undergo the MRI exam due to high creatinine level or claustrophobic will be disc loud from the MRI part.
* Informed written consent must be sought according to ICH/EU GCP, before subject registration.

Exclusion Criteria:

* Previous cancer with a terminal prognosis of less than five years.
* Previous prostate cancer

Primary outcomes:
measure: Prevalence, stage and pathology of screen-detected prostate cancer in BRCA1/BRCA2 founder mutation carriers and Lynch mutation carriers
timeFrame: within 2 years
Secondary outcomes:
measure: Accuracy of different screening tests (PSA, free to total PSA, prostate MRI) in detecting prostate cancer among men with genetic predispositions.
timeFrame: within 2 years
Other outcomes:
measure: Accuracy of different screening tests (PSA, free to total PSA, prostate MRI) in detecting clinically significant prostate cancer among men with genetic predispositions.
timeFrame: within 2 years
measure: Cost effectiveness of different screening tests (PSA, free to total PSA, prostate MRI) in detecting prostate cancer and clinically significant prostate cancer among men with genetic predispositions.
timeFrame: within 2 years
measure: Impact of genetic mutations (BRCA, Lynch) on lower urinary tract symptoms (IPSS, flow and post void urine residual) and BPH ( benign prostatic hyperplasia).
timeFrame: within 2 years
measure: Genomic and biological profiles in samples from BRCA and Lynch mutation carriers and characterize changes related to prostate cancer.
timeFrame: within 2 years
Locations:
city: Petah Tikva
country: Israel
facility: Rabin Medical Center - Beilinson Hospital
city: Petah Tikva
country: Israel
facility: Rabin Medical Center, Beilinson Hospital
Study officials:
affiliation: Rabn Medical Center, Beilinson Campus
name: David Margel, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Segal N, Ber Y, Benjaminov O, Tamir S, Yakimov M, Kedar I, Rosenbaum E, Sela S, Ozalvo R, Shavit-Grievink L, Keder D, Baniel J, Margel D. Imaging-based prostate cancer screening among BRCA mutation carriers-results from the first round of screening. Ann Oncol. 2020 Nov;31(11):1545-1552. doi: 10.1016/j.annonc.2020.06.025. Epub 2020 Sep 18.
citation: Margel D, Benjaminov O, Ozalvo R, Shavit Grievink L, Kedar I, Yerushalmi R, Ben-Aharon I, Neiman V, Yossepowitch O, Kedar D, Levy Z, Shohat M, Brenner B, Baniel J, Rosenbaum E. Personalized prostate cancer screening among men with high risk genetic predisposition- study protocol for a prospective cohort study. BMC Cancer. 2014 Jul 21;14:528. doi: 10.1186/1471-2407-14-528.