Prostate Cancer Screening Among Men With High Risk Genetic Predisposition

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Rabin Medical Center
Sponsor:
Information provided by (Responsible Party):
david margel, Rabin Medical Center
ClinicalTrials.gov Identifier:
NCT02053805
First received: January 30, 2014
Last updated: June 9, 2014
Last verified: June 2014
  Purpose

Prostate cancer screening among the general population is highly debatable. Prior data suggests that men carrying mutations in the BRCA1& 2 (BReast CAncer) genes and LYNCH Syndrome (MMR genes - MisMatching Repair gene) maybe at increased risk of developing prostate cancer.

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

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. Finally, this study will identify an inception cohort for future interventional studies of primary and secondary prevention.


Condition Intervention
BRCA1 Syndrome
BRCA2 Syndrome
Lynch Syndrome
Procedure: PSA and free to total PSA
Other: IPSS questionnaire
Procedure: DRE (Digital Rectal Examination )
Procedure: urine flow and residual
Procedure: a multiparametric prostate MRI
Procedure: trans-rectal ultra-sound guided prostate biopsy

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Screening
Official Title: Personalized Prostate Cancer Screening Among Men With High Risk Genetic Predisposition- a Prospective Cohort Study

Resource links provided by NLM:


Further study details as provided by Rabin Medical Center:

Primary Outcome Measures:
  • Prevalence, stage and pathology of screen-detected prostate cancer in BRCA1/BRCA2 founder mutation carriers and Lynch mutation carriers [ Time Frame: within 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Accuracy of different screening tests (PSA, free to total PSA, prostate MRI) in detecting prostate cancer among men with genetic predispositions. [ Time Frame: within 2 years ] [ Designated as safety issue: No ]

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. [ Time Frame: within 2 years ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: within 2 years ] [ Designated as safety issue: No ]
  • Impact of genetic mutations (BRCA, Lynch) on lower urinary tract symptoms (IPSS, flow and post void urine residual) and BPH ( benign prostatic hyperplasia). [ Time Frame: within 2 years ] [ Designated as safety issue: No ]
  • Genomic and biological profiles in samples from BRCA and Lynch mutation carriers and characterize changes related to prostate cancer. [ Time Frame: within 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 220
Study Start Date: February 2014
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
screening tests
The screening will include: DRE, PSA and free to total PSA, a multiparametric prostate MRI and a trans-rectal ultra-sound guided prostate biopsy, IPSS questionnaire, trans-rectal US assessment of prostate size, urine flow and residual.
Procedure: PSA and free to total PSA
PSA, free to total PSA. Serum will be stored for future investigations
Other: IPSS questionnaire
the validated International Prostate Symptom Score
Procedure: DRE (Digital Rectal Examination ) Procedure: urine flow and residual
The post void residual will be recorded by using ultrasound. Creatinine level will be checked.
Procedure: a multiparametric prostate MRI Procedure: trans-rectal ultra-sound guided prostate biopsy
12 core Trans-rectal prostatic biopsy for diagnostic purposes

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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)
  • No previous history of prostate cancer
  • No previous prostate biopsy
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02053805

Locations
Israel
Rabin Medical Center, Beilinson Hospital Recruiting
Petah Tikva, Israel
Contact: David Margel, MD PhD    +972(0)39378089      
Contact: Rachel Ozalvo    +972(0)39378089      
Principal Investigator: David Margel, MD Phd         
Sponsors and Collaborators
david margel
  More Information

Publications:
Mitra AV, Bancroft EK, Barbachano Y, Page EC, Foster CS, Jameson C, Mitchell G, Lindeman GJ, Stapleton A, Suthers G, Evans DG, Cruger D, Blanco I, Mercer C, Kirk J, Maehle L, Hodgson S, Walker L, Izatt L, Douglas F, Tucker K, Dorkins H, Clowes V, Male A, Donaldson A, Brewer C, Doherty R, Bulman B, Osther PJ, Salinas M, Eccles D, Axcrona K, Jobson I, Newcombe B, Cybulski C, Rubinstein WS, Buys S, Townshend S, Friedman E, Domchek S, Ramon Y Cajal T, Spigelman A, Teo SH, Nicolai N, Aaronson N, Ardern-Jones A, Bangma C, Dearnaley D, Eyfjord J, Falconer A, Grönberg H, Hamdy F, Johannsson O, Khoo V, Kote-Jarai Z, Lilja H, Lubinski J, Melia J, Moynihan C, Peock S, Rennert G, Schröder F, Sibley P, Suri M, Wilson P, Bignon YJ, Strom S, Tischkowitz M, Liljegren A, Ilencikova D, Abele A, Kyriacou K, van Asperen C, Kiemeney L; IMPACT Study Collaborators, Easton DF, Eeles RA. Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study. BJU Int. 2011 Jan;107(1):28-39. doi: 10.1111/j.1464-410X.2010.09648.x. Epub 2010 Sep 14.
Mulligan AM, Couch FJ, Barrowdale D, Domchek SM, Eccles D, Nevanlinna H, Ramus SJ, Robson M, Sherman M, Spurdle AB, Wappenschmidt B, Lee A, McGuffog L, Healey S, Sinilnikova OM, Janavicius R, Hansen Tv, Nielsen FC, Ejlertsen B, Osorio A, Muñoz-Repeto I, Durán M, Godino J, Pertesi M, Benítez J, Peterlongo P, Manoukian S, Peissel B, Zaffaroni D, Cattaneo E, Bonanni B, Viel A, Pasini B, Papi L, Ottini L, Savarese A, Bernard L, Radice P, Hamann U, Verheus M, Meijers-Heijboer HE, Wijnen J, Gómez García EB, Nelen MR, Kets CM, Seynaeve C, Tilanus-Linthorst MM, van der Luijt RB, van Os T, Rookus M, Frost D, Jones JL, Evans DG, Lalloo F, Eeles R, Izatt L, Adlard J, Davidson R, Cook J, Donaldson A, Dorkins H, Gregory H, Eason J, Houghton C, Barwell J, Side LE, McCann E, Murray A, Peock S, Godwin AK, Schmutzler RK, Rhiem K, Engel C, Meindl A, Ruehl I, Arnold N, Niederacher D, Sutter C, Deissler H, Gadzicki D, Kast K, Preisler-Adams S, Varon-Mateeva R, Schoenbuchner I, Fiebig B, Heinritz W, Schäfer D, Gevensleben H, Caux-Moncoutier V, Fassy-Colcombet M, Cornelis F, Mazoyer S, Léoné M, Boutry-Kryza N, Hardouin A, Berthet P, Muller D, Fricker JP, Mortemousque I, Pujol P, Coupier I, Lebrun M, Kientz C, Longy M, Sevenet N, Stoppa-Lyonnet D, Isaacs C, Caldes T, de la Hoya M, Heikkinen T, Aittomäki K, Blanco I, Lazaro C, Barkardottir RB, Soucy P, Dumont M, Simard J, Montagna M, Tognazzo S, D'Andrea E, Fox S, Yan M, Rebbeck T, Olopade O, Weitzel JN, Lynch HT, Ganz PA, Tomlinson GE, Wang X, Fredericksen Z, Pankratz VS, Lindor NM, Szabo C, Offit K, Sakr R, Gaudet M, Bhatia J, Kauff N, Singer CF, Tea MK, Gschwantler-Kaulich D, Fink-Retter A, Mai PL, Greene MH, Imyanitov E, O'Malley FP, Ozcelik H, Glendon G, Toland AE, Gerdes AM, Thomassen M, Kruse TA, Jensen UB, Skytte AB, Caligo MA, Soller M, Henriksson K, Wachenfeldt vA, Arver B, Stenmark-Askmalm M, Karlsson P, Ding YC, Neuhausen SL, Beattie M, Pharoah PD, Moysich KB, Nathanson KL, Karlan BY, Gross J, John EM, Daly MB, Buys SM, Southey MC, Hopper JL, Terry MB, Chung W, Miron AF, Goldgar D, Chenevix-Trench G, Easton DF, Andrulis IL, Antoniou AC; Breast Cancer Family Registry; EMBRACE; GEMO Study Collaborators; HEBON; kConFab Investigators; Ontario Cancer Genetics Network; SWE-BRCA; CIMBA. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2. Breast Cancer Res. 2011;13(6):R110. doi: 10.1186/bcr3052. Epub 2011 Nov 2.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: david margel, D Margel, MD PhD, Rabin Medical Center
ClinicalTrials.gov Identifier: NCT02053805     History of Changes
Other Study ID Numbers: 0582_13_RMC
Study First Received: January 30, 2014
Last Updated: June 9, 2014
Health Authority: Israel: Ministry of Health

Keywords provided by Rabin Medical Center:
prostate cancer, BRCA germ-line mutation, Lynch syndrome, BRCA1 Syndrome,
BRCA2 Syndrome,

Additional relevant MeSH terms:
Disease Susceptibility
Prostatic Neoplasms
Genetic Predisposition to Disease
Colorectal Neoplasms, Hereditary Nonpolyposis
Disease Attributes
Pathologic Processes
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplastic Syndromes, Hereditary
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on August 28, 2014