Prostate Cancer Screening Among Men With High Risk Genetic Predisposition

Sponsor

Rabin Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT02053805

Collaborator

(none)

200

Enrollment

Locations

Arm

63.9

Duration (Months)

100

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
BRCA1 Syndrome BRCA2 Syndrome Lynch Syndrome	Other: PSA Other: IPSS questionnaire Other: DRE (Digital Rectal Examination ) Other: urine flow and residual Procedure: a multiparametric prostate MRI Procedure: trans-rectal ultra-sound guided prostate biopsy	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Screening

Official Title:

Personalized Prostate Cancer Screening Among Men With High Risk Genetic Predisposition- a Prospective Cohort Study

Study Start Date :

Feb 1, 2014

Anticipated Primary Completion Date :

Jun 1, 2018

Anticipated Study Completion Date :

Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: screening tests The screening will include: DRE, PSA , a multiparametric prostate MRI and a trans-rectal ultra-sound guided prostate biopsy/ MRI-US fusion , IPSS questionnaire, trans-rectal US assessment of prostate size, urine flow and residual.	Other: PSA PSA. Serum & plasma will be stored for future investigations Other: IPSS questionnaire the validated International Prostate Symptom Score Other: DRE (Digital Rectal Examination ) physical examination for the prostate gland Other: urine flow and residual The post void residual will be recorded by using ultrasound. Creatinine level will be checked. Procedure: a multiparametric prostate MRI The MRI will be reported on a 5 point Likert Scale Procedure: trans-rectal ultra-sound guided prostate biopsy 12 core Trans-rectal prostatic biopsy for diagnostic purposes

Arm

Intervention/Treatment

Other: screening tests

The screening will include: DRE, PSA , a multiparametric prostate MRI and a trans-rectal ultra-sound guided prostate biopsy/ MRI-US fusion , IPSS questionnaire, trans-rectal US assessment of prostate size, urine flow and residual.

Other: PSA

PSA. Serum & plasma will be stored for future investigations

Other: IPSS questionnaire

the validated International Prostate Symptom Score

Other: DRE (Digital Rectal Examination )

physical examination for the prostate gland

Other: urine flow and residual

The post void residual will be recorded by using ultrasound. Creatinine level will be checked.

Procedure: a multiparametric prostate MRI

The MRI will be reported on a 5 point Likert Scale

Procedure: trans-rectal ultra-sound guided prostate biopsy

12 core Trans-rectal prostatic biopsy for diagnostic purposes

Outcome Measures

Primary Outcome Measures

Prevalence, stage and pathology of screen-detected prostate cancer in BRCA1/BRCA2 founder mutation carriers and Lynch mutation carriers [within 2 years]

Secondary Outcome Measures

Accuracy of different screening tests (PSA, free to total PSA, prostate MRI) in detecting prostate cancer among men with genetic predispositions. [within 2 years]

Other Outcome Measures

Accuracy of different screening tests (PSA, free to total PSA, prostate MRI) in detecting clinically significant prostate cancer among men with genetic predispositions. [within 2 years]
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. [within 2 years]
Impact of genetic mutations (BRCA, Lynch) on lower urinary tract symptoms (IPSS, flow and post void urine residual) and BPH ( benign prostatic hyperplasia). [within 2 years]
Genomic and biological profiles in samples from BRCA and Lynch mutation carriers and characterize changes related to prostate cancer. [within 2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 70 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.