Clinical trial NCT05810467: The Active Surveillance Study
Official title: Active Surveillance Study for Prostate Cancer Management for Men At Higher Genetic Risk Compared with Men At No Known Higher Genetic Risk.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Prostate Cancer
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
Collaborators: name: Royal Marsden NHS Foundation Trust
First posted: 2023-04-12
Enrollment: 200
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * Control group (i.e., no known high PrCa risk): 100 men
* Men at genetically higher PrCa risk: 100 men

Brief summary: The Active Surveillance study is a prospective study developed to look at the association of biomarkers with PrCa presentation and progression among men on Active Surveillance and stratify it by their genetic risk. This study will also investigate the incidence and progression by differing genetic risks.

Detailed description: This prospective study will look at the association of biomarkers with PrCa presentation and progression among men on Active Surveillance and stratify it by their genetic risk. This study will also investigate the incidence and progression by differing genetic risks. The study will review the serial PSA and imaging data for men in AS comparing and contrasting the men of known higher genetic risk for PrCa with those without. Additionally, the study aims to collect samples to investigate the profile of plasma, serum, urine, stool and saliva biomarkers in men at a higher genetic risk of PrCa, who have been diagnosed with low risk PrCa and are undergoing Active Surveillance. It will also review the association of specific genetic profiles and biomarkers (biological samples - plasma, serum, urine, stool and saliva). These markers will be compared and contrasted with samples from men with no known increased genetic risk for PrCa.

The study aims to recruit a total of 200 men with low grade PrCa, aged ≥18 into two cohorts (i.e. men on AS who are known to be at higher genetic risk and those on AS with no known increased genetic risk of PrCa. Patients will be identified through the urology clinics at the Royal Marsden Hospital. These will be men who are already registered at the Royal Marsden Hospital and undergoing active surveillance (as determined by the MDT).

Eligibility criteria: Inclusion Criteria:

* Men ≥18 years old under the care of the Active Surveillance clinic in the Royal Marsden Hospital (RMH).
* Known diagnosis of PrCa, deemed suitable for Active surveillance at multi-disciplinary meeting (MDT).
* Men at genetically higher PrCa risk who are either:

  1. Men of European ancestry with a positive family history of PrCa defined as:

     * Having a first degree relative (or second degree if through female line) with histologically or death certificate proven PrCa diagnosed at \<70 years
     * Having 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
     * Having three relatives on the same side of the family with histologically or death certificate proven PrCa diagnosed at any age

Or (2) Men of black African or Caribbean ancestry defined as:

- Both parents and all 4 grandparents from that origin Or (3) Men with a pathogenic mutation in a gene thought to cause a higher risk of prostate cancer: (including BRCA1, BRCA2, ATM, PALB2, MLH1, MSH2, MSH6, CHEK2 and other DNA repair gene mutations as listed in appendix A) Or (4) Men with a high genetic risk (common and/or rare variants) for PrCa resulting in a RR of ≥2 of PrCa

* Men with no known high risk genetic factors who have been diagnosed with low grade PrCa and deemed suitable for Active Surveillance at multi-disciplinary meeting (control group) as defined in the 4 criteria above.
* Who performance status 0-2 (see Appendix B)
* Absence of any psychological, familial, sociological, or geographical situation potentially hampering compliance with the study protocol and follow-up schedule.

Exclusion Criteria:

* No PrCa diagnosis
* PrCa diagnosis that is not deemed suitable for active surveillance at multi-disciplinary meeting
* Any significant psychological conditions that may be worsened or exacerbated by participation in the study

Primary outcomes:
measure: To determine the incidence of disease progression of PrCa in the cohorts studied.
timeFrame: The full analysis being completed within one year of date of completion of 5 year follow-up of the last participant.
measure: To determine the incidence of aggressiveness of PrCa in the cohorts studied.
timeFrame: The full analysis being completed within one year of date of completion of 5 year follow-up of the last participant.
Secondary outcomes:
measure: To investigate the role of biomarker profiles in men undergoing active surveillance who are also at genetically higher risk for PrCa.
timeFrame: 5 years
measure: To investigate the role of biomarker profiles in men undergoing active surveillance who are also at genetically higher risk for PrCa.
timeFrame: 5 years
Other outcomes:
Locations:
city: Sutton
country: United Kingdom
facility: Institute of Cancer Research and Royal Marsden Hospital
state: Surrey
Study officials:
affiliation: Institute of Cancer Research and Royal Marsden Hospital
name: Ros A Eeles, FRCP, FRFR
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J, Robinson M, Staffurth J, Walsh E, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Neal DE; ProtecT Study Group. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016 Oct 13;375(15):1415-1424. doi: 10.1056/NEJMoa1606220. Epub 2016 Sep 14.
citation: Tseng KS, Landis P, Epstein JI, Trock BJ, Carter HB. Risk stratification of men choosing surveillance for low risk prostate cancer. J Urol. 2010 May;183(5):1779-85. doi: 10.1016/j.juro.2010.01.001. Epub 2010 Mar 20.
citation: Bokhorst LP, Valdagni R, Rannikko A, Kakehi Y, Pickles T, Bangma CH, Roobol MJ; PRIAS study group. A Decade of Active Surveillance in the PRIAS Study: An Update and Evaluation of the Criteria Used to Recommend a Switch to Active Treatment. Eur Urol. 2016 Dec;70(6):954-960. doi: 10.1016/j.eururo.2016.06.007. Epub 2016 Jun 19.
citation: Porten SP, Whitson JM, Cowan JE, Cooperberg MR, Shinohara K, Perez N, Greene KL, Meng MV, Carroll PR. Changes in prostate cancer grade on serial biopsy in men undergoing active surveillance. J Clin Oncol. 2011 Jul 10;29(20):2795-800. doi: 10.1200/JCO.2010.33.0134. Epub 2011 May 31.
citation: Berglund RK, Masterson TA, Vora KC, Eggener SE, Eastham JA, Guillonneau BD. Pathological upgrading and up staging with immediate repeat biopsy in patients eligible for active surveillance. J Urol. 2008 Nov;180(5):1964-7; discussion 1967-8. doi: 10.1016/j.juro.2008.07.051. Epub 2008 Sep 17.