The PROFILE Study: Germline Genetic Profiling: Correlation With Targeted Prostate Cancer Screening and Treatment
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,600
- 试验地点
- 1
- 主要终点
- The association of specific genetic profiles and biomarkers to predict outcome of prostate screening in men at higher genetic risk
研究概览
简要总结
Prostate cancer is now the most common cancer in men in the Western world. In the United Kingdom (UK), there were over 52,000 new cases diagnosed in 2016-2018 and a lifetime risk of 1 in 8. Prostate cancer (PrCa) can run in some families and research studies have identified several genetic changes in Caucasian populations that are thought to increase the risk of developing prostate cancer. Other studies have shown that men from certain ethnic groups also have a higher risk of prostate cancer, and this includes men of black African or black African-Caribbean ancestry. This study aims to look at men with a higher risk of prostate cancer based on their ethnicity, family history and/or genetic predisposition to see whether any of these genetic changes are present in their DNA (genetic material) and whether this could be a helpful screening tool in prostate cancer screening programmes. It is thought that many genetic changes are involved in the development of prostate cancer and research is being carried out worldwide to identify these genetic changes. Some of these changes may cause a very slight increase in prostate cancer risk while others may cause a much larger increase in risk of developing prostate cancer. The investigators will invite (i) men of any ethnicity with a family history of prostate cancer; (ii) men of black African or black African-Caribbean ancestry; and (iii) men of any ethnicity with a known genetic predisposition to having prostate cancer (e.g., being known to have inherited a gene mutation that increases risk of prostate and/or being known to be in the top tenth percentile of the polygenic risk score (high PRS score prior to enrolment) for targeted prostate screening (Prostate Specific Antigen (PSA) testing, MRI and a biopsy of the prostate gland) and genetic profiling. The outcome of these prostate cancer screening investigations will be compared with the genetic profiles of those taking part in the study in order to look for certain genetic changes in the gene code that are thought to increase prostate cancer risk. This research will help us to determine what the role of such genetic profiling is in a prostate cancer screening programme and if it helps identify men at high prostate cancer risk.
详细描述
Purpose and Design
The aim of the PROFILE study is to investigate the role of targeted prostate cancer screening in men at a genetically higher risk to estimate the incidence of PrCa and the sensitivity and specificity of PSA screening in these populations and correlate this with genetic profiles and biological endpoints. Additionally, the study aims to identify biomarkers from biological samples (such as blood and urine) as well as imaging technologies (e.g. MRI and new imaging techniques) as predictive markers of the risk of developing PrCa and to correlate these with genetic risk. This study has been designed using an observational approach to look at the correlation of cancer incidence (on biopsy) with genetic profile. The aim is to evaluate targeted screening for prostate cancer in men at a genetically higher risk to estimate the incidence of prostate cancer and the sensitivity and specificity of PSA screening in these populations and correlate this with genetic profiles (i.e. single nucleotide polymorphism (SNP) profiles) and biological endpoints.
Three cohorts will be recruited:
- Men of any ethnicity with family history of prostate cancer.
- Men of black African or black African-Caribbean ancestry.
- Men of any ethnicity with a genetic predisposition to having prostate cancer (e.g., being known to have inherited a gene mutation that increases risk of prostate cancer (i.e. high-risk gene mutation) and/or being known to have a high polygenic risk score (high PRS score) defined as being in the top tenth percentile prior to enrolment.
Men with no prior screening will be offered biopsy and genetic profiling. This will provide data on genetic profiling and correlation with biopsy irrespective of PSA in men who have not had any previous screening.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 40 Years 至 69 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Men of any ethnicity with a positive family history of PrCa defined as:
- •Men with a first degree relative (or second degree if through female line) with histologically or death certificate proven PrCa diagnosed at <70 years
- •Men with two relatives on the same side of the family with histologically or death certificate proven PrCa where at least one is diagnosed at <70 years
- •Men with three relatives on the same side of the family with histologically or death certificate proven PrCa diagnosed at any age
- •Men of black African or black African-Caribbean ancestry defined as:
- •Both parents and all 4 grandparents being of either black African or black African-Caribbean ancestry.
- •Men of any ethnicity with a genetic predisposition to having prostate cancer e.g., being known to have inherited a gene mutation that increases risk of prostate cancer (e.g. BRCA1, BRCA2, ATM, PALB2, MLH1, MSH2, MSH6, CHEK2 and other DNA repair gene mutations as listed in the study protocol); and/or being known to have a high polygenic risk score (PRS) (defined as being in the top tenth percentile prior to enrolment).
- •Age 40- 69 years
- •WHO performance status 0-2
- •Absence of any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow up schedule.
排除标准
- •Previous cancer with a life expectancy of less than five years.
- •Previous PrCa
- •Negative biopsy within one year before recruitment
- •Co-morbidities making prostate biopsy risk unacceptable (anticoagulants or antiplatelet medication including Warfarin, Clopidogrel, Apixaban, Dabigatran or other NOAC (Novel Oral Anti-Coagulant); poorly controlled diabetes, cardiovascular/respiratory disease, immunosuppressive medication or splenectomy)
- •Men with body mass index (BMI) 40 and above.
- •Men with BMI 35 and above plus other co-morbidities.
- •Contraindications to having an MRI (non-MRI compliant pacemakers, aneurysm clips, metallic cardiac valve/stent, Ventriculo-Peritoneal (VP) shunt, cochlear implant, neurotransmitter, metallic foreign bodies in eye(s), other metalwork, claustrophobia)
- •Any significant psychological conditions that may be worsened or exacerbated by participation in the study
结局指标
主要结局
The association of specific genetic profiles and biomarkers to predict outcome of prostate screening in men at higher genetic risk
时间窗: 5 years
To investigate the role of targeted prostate cancer screening in men at higher genetic risk (i.e. family history, ethnicity, gene mutation status), its association with specific genetic profiles and biomarkers as predictive tools of the risk of developing prostate cancer and to correlate these with genetic risk.
次要结局
- The incidence and aggressiveness of prostate cancer in men at higher genetic risk.(5 years)
- The association of Diffusion Weighted MRI (DW-MRI) findings with prostate biopsy results.(5 years)
- The incidence of abnormal imaging (using 3D ultrasound combined with shear wave elastography) and correlation with biopsy outcome and to correlate standard 12 core prostate biopsies with targeted biopsies based on abnormalities identified at DWMRI.(5 years)
- The association of quantitative imaging biomarkers with prostate biopsy result(5 years)
- The association of biological sample biomarker profiles with prostate biopsy result.(5 years)