The IMPACT Study - Identification of Men With a Genetic Predisposition to ProstAte Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT00261456
Recruitment Status : Recruiting
First Posted : December 5, 2005
Last Update Posted : August 31, 2018
Cancer Research UK
Royal Marsden NHS Foundation Trust
Ronald and Rita McAulay Foundation
Information provided by (Responsible Party):
Institute of Cancer Research, United Kingdom

December 1, 2005
December 5, 2005
August 31, 2018
October 2005
December 2019   (Final data collection date for primary outcome measure)
Not Provided
Not Provided
Complete list of historical versions of study NCT00261456 on Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
The IMPACT Study - Identification of Men With a Genetic Predisposition to ProstAte Cancer
The IMPACT Study - Identification of Men With a Genetic Predisposition to ProstAte Cancer: Targeted Screening in BRCA1/2 Mutation Carriers & Controls

The IMPACT study is an international targeted prostate screening study of men at increased prostate cancer risk due to the presence of known pathogenic mutations in BRCA1 and BRCA2 genes.

There are only approximately 150 men with a known BRCA1 or BRCA2 mutation in the UK. Research has shown that these men are at an increased risk of developing prostate cancer but more information is needed about the pathogenesis of prostate cancer in this defined group and the role of screening in these men. The study will offer annual PSA screening to these men to determine the incidence of prostate cancer in this group. The study will also look at new markers of early prostate cancer in this cohort.

The power calculations for this study are 850 carriers and 850 controls (age-matched men without BRCA1/2 mutations). It is therefore essential to gain international collaboration to meet the target of recruiting 850 men with these known mutations and a control group of 850 men who have tested negative for a known familial mutation.

Prostate cancer is a significant public health problem. In the EU approximately 200,000 men are diagnosed annually with prostate cancer. There are 24,000 cases per year in England and Wales and 10,000 deaths. The incidence is increasing, even when screen-detected cancers are considered, and within the next few years it will become the most common cancer in UK men.

that an alteration in the breast cancer predisposition genes BRCA1 and BRCA2, may predispose to prostate cancer (PC) and this study will increase this evidence-base. There is some evidence, at least in BRCA2 carriers, that the prostate cancer in these men may be more aggressive and so earlier detection could theoretically reduce mortality. It has been reported that unaffected individuals from families with multiple cases of PC show an increased percentage of raised PSA levels, but the use of PSA level and its predictive value in healthy males with BRCA1/2 mutations has not been studied. If PSA were to be used as a screening tool in BRCA1/2 mutation carriers, we would need to gain a better understanding of the pathogenesis of PC in these men and determine whether they have a different baseline PSA profile compared with controls.

The high prevalence of hormone-dependent/secreting tumours such as breast, ovary and prostate in BRCA1/2 carriers suggests an important role of hormones and their receptors in the development of cancer. Androgens and androgen receptors are considered crucial elements in PC pathogenesis. Therefore male sex hormones will be measured to determine the hormone profile in BRCA1/2 carriers compared with a control group. There is strong evidence that BRCA1/2 play an important role in DNA repair and cell cycling. Therefore, we will investigate abnormalities of the metabolic processes in individuals with a BRCA1/2 mutation where cell cycling may be abnormal. Analysis of proteins (proteomics) and metabolites (metabonomics) are powerful approaches to identifying proteins and metabolites involved in cancer formation. The analysis of the proteins and metabolites will enable us to investigate the effect of the presence of a BRCA1/2 mutation and aid in the identification of new biomarkers for prostate cancer.

The target population is a group of 850 males who carry a known pathogenic mutation in the BRCA1/2 genes (500 BRCA1 and 350 BRCA2). These men will be recruited through genetics clinics across the UK and the world. A control group of men who have tested negative for a known pathogenic mutation that is running in their family will also be recruited through the genetics clinics.

All participants will be invited to attend annually for 5 years for an appointment lasting approximately 30 minutes during which they will discuss the study in detail before giving their written consent agreeing to participate. They will have a 50ml blood sample taken and be asked to provide a urine sample every year. They will also be required to complete a short family and medical history questionnaire. These appointments will either take place at the centre they are registered at, at the Royal Marsden Hospital, or in their own home depending on the arrangements made with the collaborating consultant and patient preference.

The PSA level of all participants will be measured locally. If PSA is >3.0ng/ml, a ten core prostatic biopsy will be offered, carried out by a consultant urologist. Ten biopsies will be used for diagnostic purposes, with two extra biopsy samples taken for research analysis with the patients fully informed written consent prior to the procedure being carried out. If any of the ten cores identify the presence of prostate cancer, they will receive treatment for this as advised by their local centre. The PSA will be quality controlled by batch testing at a reference lab. If the value locally was <3.0ng/ml but is >3ng/ml in the reference lab it will be remeasured locally.

If high grade Prostatic Intraepithelial Neoplasia (PIN) is detected or if the sample is inconclusive then a sextant biopsy repeated after 6 weeks will be recommended, in accordance with the ERSPC protocol. If atypical acini are detected then immediate biopsy will be undertaken.

Observational Model: Case-Control
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Whole blood, Serum, Plasma, Urine, Prostate tissue.
Non-Probability Sample
Any patient that meets the eligibility criteria and maybe attending a genetics clinic at a number of international centres that have gone through ethical approval.
Prostate Cancer in BRCA1 and BRCA2 Carriers
  • Behavioral: PSA test
    Patients tested for their level of Prostate Specific Antigen.
  • Procedure: Prostate Biopsy
    A Prostate biopsy is given as an option to the patient if their PSA level is raised or at the end of 5 years screening.
  • BRCA1/2 carriers
    Carriers of a BRCA1 or BRCA2 mutation.
    • Behavioral: PSA test
    • Procedure: Prostate Biopsy
  • BRCA1/2/non Carriers
    Do not carry a mutation in either the BRCA1 or 2 genes that has been found in other members of the family.
    • Behavioral: PSA test
    • Procedure: Prostate Biopsy

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
December 2021
December 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male carriers of a known pathogenic BRCA1/2 mutations or men testing negative for a known BRCA1/2 mutation in their family
  • Aged between 40-69 years old
  • WHO performance status 0-2
  • No previous history of prostate cancer
  • No previous prostate biopsy for raised PSA
  • Absence of any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow-up schedule
  • Fully informed, written consent according to ICH/EU GCP and national/local regulations before subject registration.

Exclusion Criteria:

  • Previous cancer with terminal prognosis of less than 5 years
  • Previous prostate cancer
Sexes Eligible for Study: Male
40 Years to 69 Years   (Adult, Older Adult)
Contact: Rosalind A Eeles, FRCP FRCR 44 208 661 3642
Contact: Elizabeth K Bancroft, RGN MMedSci 44 207 808 2136
United Kingdom
CCR2598 ( Other Identifier: CCR )
Not Provided
Plan to Share IPD: Yes
Plan Description: Anonymised data can be applied for via the Data Access Committee
Institute of Cancer Research, United Kingdom
Institute of Cancer Research, United Kingdom
  • Cancer Research UK
  • Royal Marsden NHS Foundation Trust
  • Ronald and Rita McAulay Foundation
Principal Investigator: Rosalind A Eeles, FRCP FRCR Institute of Cancer Research and Royal Marsden Hospital
Institute of Cancer Research, United Kingdom
August 2018