A randomised phase 3 trial evaluating the role of finasteride in increasing compliance with active surveillance, in men with a new diagnosis of low and intermediate risk prostate cancer, when compared with usual care.
| ISRCTN | ISRCTN16867955 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16867955 |
| EudraCT/CTIS number | 2021-004004-17 |
| IRAS number | 1004290 |
| Secondary identifying numbers | IRAS 1004290, STH21032 |
- Submission date
- 27/07/2021
- Registration date
- 27/08/2021
- Last edited
- 13/02/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English Summary
Background and study aims
Prostate cancer is cancer that occurs in the prostate. The prostate is a small walnut-shaped gland in males that produces the seminal fluid that nourishes and transports sperm.
Prostate cancer is the commonest cancer in men. Many prostate cancers are not lethal and can be safely managed by observation (Active Surveillance). Over time, more than half of the men choosing observation receive radical surgery or radiotherapy. Both treatments produce side effects and may be unnecessary. Most men opt for treatment because of their rising PSA (prostate blood test) levels. This usually reflects aging of the prostate, rather than advancing cancer.
We aim to improve what is offered, so more men remain on observation. We believe a drug called finasteride may help. Finasteride slows prostate growth and reduces PSA levels. Finasteride has few side effects and has been shown to reduce the risk of a man developing prostate cancer. We predict that finasteride will reduce the number of men receiving radical treatment from 20% to 10% at 4 years.
Who can participate?
Men aged 50 – 75 years who are receiving observation for low/intermediate-risk prostate cancer
What does the study involve?
We will randomise 550 men receiving observation for low/intermediate risk prostate cancer to either finasteride or usual care. All men will receive Active Surveillance; including PSA testing (3 monthly year 1 and 6 monthly years 2/3) and MRI scanning (at year 1 and 3). Prostate biopsies will be used for men with changing MRI scans and at year 3.
What are the possible benefits and risks of participating?
Benefits: Participants may benefit from the medication used
Risks: Potential participants will be informed of all the possible risks associated with taking finasteride, and they will also be documented in the Patient Information Leaflet (PIS). Common side effects: Impotence, Decreased libido, Decreased volume of ejaculate
Where is the study run from?
University of Sheffield (UK)
When is the study starting and how long is it expected to run for?
April 2021 to December 2027
Who is funding the study?
Yorkshire Cancer Research (UK)
Who is the main contact?
1. Prof Jim Catto, j.catto@sheffield.ac.uk
2. Finesse study team, cptu-finesse@qmul.ac.uk
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-finasteride-and-active-surveillance-for-newly-diagnosed-prostate-cancer
Contact information
Public, Scientific
Academic Units of Urology and Molecular Oncology
Department of Oncology and Metabolism
University of Sheffield
GU22, G Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX
United Kingdom
 ORCID ID |
0000-0003-2787-8828 |
|---|---|
| Phone | +44 (0)114 215 9002 |
| j.catto@sheffield.ac.uk |
Public
Cancer Prevention Trials Unit (CPTU) Cancer Prevention Group
1st Floor Empire House
Queen Mary University of London Whitechapel
67-75 New Road
London
E1 1HH
United Kingdom
| Phone | +44 (0)20 7848 9705 |
|---|---|
| r.kealy@qmul.ac.uk |
Public
-
London
-
United Kingdom
| cptu-finesse@qmul.ac.uk |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | ISRCTN16867955_PIS_V7.0-27Mar2024.pdf |
| Scientific title | FINasteride Evaluation in active Surveillance for low and intermediate-risk prostate cancer |
| Study acronym | FINESSE |
| Study hypothesis | We aim to test if the drug finasteride can increase the adherence of men to surveillance programs and reduce radical treatment rates. Many men opt for treatment because of their rising PSA levels, which usually reflects non-cancerous enlargement of the prostate, rather than progressive/advancing cancer. We hypothesise, that the addition of finasteride to usual care, in men receiving active surveillance for prostate cancer, will increase adherence in surveillance. In turn, this will reduce the rates of radical and palliative treatment. We hypothesise, this will occur through reduced PSA values (in absolute terms) and reductions in benign PSA fluctuation. |
| Ethics approval(s) | Approved 14/12/2021, South Central – Oxford C (Oxfordshire Research Ethics Committee C) (Health Research Authority (Bristol), Ground Floor, Temple Quay House, 2 The Square, Bristol, BS1 6PN; +44 (0)207 104 8226; oxfordc.rec@hra.nhs.uk), ref: 21/SC/0349 |
| Condition | Men with a new diagnosis of low- and intermediate-risk prostate cancer |
| Intervention | FINESSE is a multicentre, open label, prospective, two-armed randomised controlled CTIMP, to test the superiority of finasteride and active surveillance over- active surveillance alone, in men with newly diagnosed low/intermediate risk localised prostate cancer. We will randomise (1:1), 550 patients to Active Surveillance with or without once daily finasteride, (5mg). Patients will receive finasteride for 2 years and will be followed up for an average of 4 years. Active surveillance will include PSA, re-biopsy and mpMRI as per usual NHS care. The primary outcome is adherence with Active Surveillance in both arms. • There are no placebo treatments for the following reasons: The PSA levels in men treated with finasteride will almost halve. Since it is necessary to monitor PSA (for AS) this would unblind both arms unless clinicians and patients were blinded to the PSA results. • Blinding PSA data would be impractical, since men may actively seek PSA tests outside the study. • It is ethical that control patients experiencing any side effects, e.g., erectile dysfunction, ejaculatory problems, or a rash, know they are independent of the treatment. • Participants unaware they are taking finasteride may opt for radical treatment earlier. This is a pragmatic trial designed to see whether knowing that they are being treated and that the treatment is having a positive impact on PSA levels would reassure men and enable them to continue with active surveillance for longer, rather than seeking radical treatment even though their disease may not have progressed. • The prohibitive costs & logistics associated with placebo-controlled trials Randomisation: A web-based randomisation system will be designed, using the bespoke KCTU randomisation system. The randomisation system will be created in collaboration with the trial analyst/s and the CI and maintained by the King’s Clinical Trials Unit for the duration of the project. It will be hosted on a dedicated server within KCL. Finasteride: Patients randomised to the treatment arm will receive once a day 5mg finasteride for two years in addition to Active Surveillance. Finasteride dispensing will be performed by the hospital pharmacy, with 3 monthly dispensing, and any visits required outside of routine AS appointments (for PSA testing or mpMRI) will have travel expenses reimbursed. Men may remain on finasteride, after 2 years, if they choose to. Pharmacovigilance reporting will continue for one month post the last finasteride treatment. Any side effects or adverse events (AEs) related to the study drug will be reported to the research nurse at study visits, and reasons for withdrawal from Finasteride will be captured. A safety analysis of the study drug will be completed at the end of the study, with yearly safety updates (Development Safety Update Reports - DSURs) to the MHRA. Active Surveillance: Men will be monitored using a combination of: • Digital Rectal examination (DRE) and PSA measurement will be performed 3 monthly in year 1, 6 monthly in all subsequent years within this trial (2-5 years) • MRI at 12 months and 36 months after diagnosis. Further MRIs will be indicated when PSA kinetics breach prespecified thresholds (Doubling Time (DT) < 3 years), or when clinical examination suggests progressive disease. • Prostate biopsy will be performed in men with clinical, biochemical progression (PSA DT <3 years) or radiological progression (increasing disease burden on MRI) or at 36 months after diagnosis (after the 36 month MRI). Follow up: After trial completion, we will recommend annual surveillance in the community (by their GP) for men with stable prostate cancer. In men with fluctuating or concerning parameters, we will recommend surveillance by their referring urologist. Sample size: We estimate finasteride will reduce radical treatment rates by 50% (from 20% to 10%) after an average of 4 years follow-up. The sample size is based on waning 90% power to detect a significant difference (using a two-sided log-rank test with alpha=0.05) assuming that 50% of control patients will progress (or be treated) during follow-up and that the hazard ratio is 0.65. The exact number needed is 271 per arm. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Finasteride |
| Primary outcome measure | Adherence with Active Surveillance at 2 and 5 years after diagnosis. Adherence is defined as the absence of a change in treatment to radical therapy or treatment of advanced disease measured using patient records. |
| Secondary outcome measures | 1. Quality of life measured using EQ-5D-5L , EORTC QLQ C30, EPIC, EORTC QLQ FA12, Memorial Anxiety Scale PC, DASS 21, completed at 3, 6, 12, 18, 24, 36, 48 and 60 months 2. Compliance with and tolerability of finasteride measured in the Finasteride arm by summary of tablets returned count (median and minimum, maximum) at the end of treatment 3. Satisfaction and quality of decision-making measured using Decisional Conflict Scale, Subjective decision quality scale, Decisional regret scale at 3, 6, 12, 18, 24, 36, 48 and 60 4. Side effects of finasteride measured using the count of adverse events in Finasteride arm. All adverse events occurring during the 3-5 year follow-up of the study 5. Prostate cancer progression measured using mpmpMRI stage, Increase in biopsy grade, Using prostatectomy histology , PSA defined progression, Clinical stage progression (using DRE), Development of radiologically proven metastases, Death from prostate cancer during the 3-5 year follow-up of the study 6. Changes in mpmpMRI appearances of the prostate over time measured using mpmpMRI scan results at baseline, 12 and 36 months 7. Views of patients, partners, para-medical and clinical staff regarding the use of finasteride within active surveillance for this disease measured using semi-structured one to one interviews with selected individuals during the follow-up phase, (months 45-54 inclusive) 8. Rate of intervention for symptoms related to benign prostate enlargement (defined as the use or oral medication (such as alpha blocker, PDE5 inhibitor or anti-cholinergic) or endoscopic prostate surgery (such as TURP, Urolift, Green light laser TURP, steam treatment, HOLEP or other) measured using patient records during the 3-5 year follow-up of the study |
| Overall study start date | 16/04/2021 |
| Overall study end date | 31/12/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 50 Years |
| Upper age limit | 75 Years |
| Sex | Male |
| Target number of participants | 550 |
| Participant inclusion criteria | Current participant inclusion criteria as of 12/12/2023: 1. Male participants: 1.1. Aged 50 to 75 years old 1.2. With an estimated life expectancy of 10 years or more 1.3. Have opted for Active Surveillance as their preferred prostate cancer therapy 2. Willing and able to provide written informed consent or if appropriate, have an acceptable individual capable of giving consent on their behalf 3. Fit enough and suitable for radical treatment 4. Eastern Oncology Performance (ECOG) status ≤ 1 (See figure one below) 5. Histopathological diagnosis of low or intermediate-risk adenocarcinoma of the prostate in the last 24 months (from the date of histology to the date of the patient’s randomisation) 6. Gleason grade group ≤ 2 (i.e. Gleason grade ≤ 3+4=7) 7. Radiological stage ≤T2c cN0 cM0 as defined by bpMRI/mpMRI imaging within the last 12 months (from the date of the bpMRI/mpMRI scan to the date of the patient’s randomisation). A copy of the bpMRI/mpMRI scan, and report confirming eligibility will be required. In this study, MX will be treated as M0, and NX will be treated as N0. 8. PSA ≤20ng/ml. The result must be within 3 months of the date of the patient’s randomisation. 9. PSA Density ≤0.2 ng/ml. The result must be within 3 months of the date of the patient’s randomisation 10. Biopsy criteria (route can be trans-rectal or trans-perineal, but must have been within the last 24 months of the patient’s randomisation date) regardless of biopsy strategy: 10.1. Maximum cancer core length is ≤ 10mm 10.2. ≤3cores involved with cancer Current participant inclusion criteria as of 16/11/2021 to 12/12/2023: 1. Male subjects aged 50 to 75 years with an estimated life expectancy of 10 years or more, who have opted for Active Surveillance as their preferred prostate cancer therapy 2. Willing and able to provide written informed consent or if appropriate, have an acceptable individual capable of giving consent on their behalf 3. Fit enough and suitable for radical treatment 4. Eastern Oncology Performance (ECOG) status ≤ 1 (See figure one below) 5. Histopathological diagnosis of low or intermediate-risk adenocarcinoma of the prostate in the last 6 months (from the date of histology to the date of the patient’s eligibility assessment) 6. Gleason grade group ≤ 2 (i.e., Gleason grade ≤ 3+4=7) 7. Radiological stage ≤T2b cN0 cM0 as defined by mpMRI imaging within the last 6 months. 8. PSA ≤20 ng/ml 9. PSA Density ≤0.2 10. Biopsy criteria (route can be trans-rectal or trans-perineal, but must have been within the last 6 months of registration): 10.1. If targeted biopsy then the maximum cancer core length is ≤10 mm 10.2. If targeted and systematic sampling biopsy then the maximum cancer core length should be ≤ 10 mm, and ≤2 or ≤15% of non-targeted cores involved with cancer. 10.3. If non-targeted biopsy (i.e., USS template or sampling irrespective of lesions) then maximum cancer core length is ≤ 10mm AND ≤3 or ≤20% of total number of cores involved with cancer Previous participant inclusion criteria: 1. Men aged 50 – 75 years with low or intermediate-risk prostate cancer diagnosed within the last 12 months 2. Informed consent 3. Willing to take part in the study |
| Participant exclusion criteria | 1. Those not fit for radical treatment 2. Those who have previously received treatment for prostate cancer (including radiotherapy, hormone therapy, brachytherapy or surgery) 3. Whose life expectancy is < 10 years 4. Either current or recent (≤12 months) treatment with finasteride or dutasteride 5. Currently enrolled or has been a participant within the last 30 days, in any other investigational drug or device study 6. Men not willing to comply with the procedural requirements of this protocol 7. Known allergy/sensitivity to, or intolerance of, finasteride or other 5-alpha reductase inhibitors, e.g., dutasteride. Known allergy to any excipients of finasteride 8. Any malignancy (other than non-melanoma skin cancer) that has not been in complete remission for five years 9. Any serious co-existent medical condition that would make repeat prostate biopsy hazardous 10. All contraindications to finasteride including concomitant therapy with any medication that may interact with finasteride 11. Any rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption 12. Men trying for a baby or with a pregnant partner |
| Recruitment start date | 15/08/2022 |
| Recruitment end date | 30/09/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Oxford
OX3 7LE
United Kingdom
Leeds
LS1 3EX
United Kingdom
Bradford
BD9 6RJ
United Kingdom
Glossop Road
Sheffield
S10 2JF
United Kingdom
Aberford Road
Wakefield
WF1 4DG
United Kingdom
Sponsor information
Hospital/treatment centre
Herries Road
Sheffield
S5 7AU
England
United Kingdom
| Phone | +44 (0)114 243 4343 |
|---|---|
| sth.researchadministration@nhs.net | |
| Website | http://www.sheffield.ac.uk/ |
"ROR" |
https://ror.org/018hjpz25 |
Funders
Funder type
Charity
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- YCR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/03/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository, Published as a supplement to the results publication |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | Current IPD sharing statement as of 30/12/2021: All data transferred between stakeholders will be covered by appropriate data sharing, data processing agreements or in the case of data transferred from trial sites to KCL, the site agreement. Trial data will be stored securely and made available for audit according to CPTU and KCTU SOPs. The Data Safe Haven for REDCap (AIMES https://www.aimes.uk/) will used to process and store data on behalf of Kings College London. The datasets generated and/or analysed during this study will be included in the subsequent results publication. _____ Previous IPD sharing statement: All data generated or analysed during this study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.0 | 14/10/2021 | 07/02/2022 | No | No |
| Protocol file | version 2.0 | 11/03/2022 | 04/04/2022 | No | No |
| Protocol file | version 3.0 | 18/05/2022 | 06/07/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 4.0 | 19/06/2023 | 02/10/2023 | No | No |
| Protocol file | version 4.0 | 27/09/2023 | 12/12/2023 | No | No |
| Participant information sheet | version 7.0 | 27/03/2024 | 22/10/2024 | No | Yes |
| Protocol file | version 5.0 | 27/03/2024 | 22/10/2024 | No | No |
| Protocol article | 11/02/2025 | 13/02/2025 | Yes | No |
Additional files
Editorial Notes
13/02/2025: Publication reference added.
22/10/2024: The following changes were made:
1. Uploaded protocol v5.0 (not peer-reviewed) and participant information sheet v7.0.
2. The recruitment end date was changed from 18/10/2024 to 30/09/2025.
3. The overall study end date was changed from 31/03/2027 to 31/12/2027.
4. The intention to publish date was changed from 01/03/2028 to 31/03/2028.
12/09/2024: The following changes were made:
1. The recruitment end date was changed from 30/09/2024 to 18/10/2024.
2. Study contacts were updated.
19/04/2024: The recruitment end date was changed from 31/03/2024 to 30/09/2024.
12/12/2023: The following changes were made:
1. Uploaded protocol v4.0 dated 27 Sept 2023 (not peer-reviewed) as an additional file.
2. A public contact was removed.
3. Mid Yorkshire Teaching NHS Trust was added as a study participating centre.
4. The participant inclusion criteria were changed.
5. The recruitment end date was changed from 01/12/2023 to 31/03/2024.
02/10/2023: The following changes have been made:
1. Uploaded protocol v4.0 (not peer-reviewed) as an additional file.
2. A study website added.
15/09/2022: Cancer Research UK plain English summary link added to plain English summary field.
04/08/2022: The recruitment start date has been changed from 01/08/2022 to 15/08/2022.
19/07/2022: The recruitment start date has been changed from 01/07/2022 to 01/08/2022.
06/07/2022: The following changes were made to the trial record:
1. Uploaded protocol v3.0 (not peer-reviewed) as an additional file.
2. A public contact has been replaced and the plain English summary updated accordingly.
06/06/2022: The recruitment start date was changed from 01/06/2022 to 01/07/2022.
10/05/2022: The recruitment start date was changed from 03/05/2022 to 01/06/2022.
04/04/2022: The following changes were made to the trial record:
1. Uploaded protocol v2.0 (not peer-reviewed) as an additional file.
2. The recruitment start date was changed from 01/04/2022 to 03/05/2022.
07/02/2022: The following changes have been made:
1. The recruitment start date has been changed from 01/02/2022 to 01/04/2022.
2. The protocol (not peer reviewed) has been uploaded as an additional file.
3. The ethics approval has been added.
11/01/2022: An ORCID has been added for one of the contacts.
10/01/2022: Two public contacts have been added and the plain English summary updated accordingly.
30/12/2021: The following changes have been made:
1. The recruitment start date has been changed from 01/12/2021 to 01/02/2022.
2. The ethics approval information has been added.
3. The IPD sharing statement has been changed.
16/11/2021: The following changes have been made:
1. The IRAS number has been added.
2. The participant inclusion criteria have been updated.
3. The trial participating centre "Royal Hallamshire Hospital" has been added.
09/09/2021: A study contact has been added.
29/07/2021: Trial's existence confirmed by Yorkshire Cancer Research.
