Prostatic NeoplasmsPhase 3ENFORCENCT04833426
Impact of Peri-operative tEstosterone Levels on oNcological and Functional Outcomes in RadiCal prostatEctomy
A Phase 3 study testing Testosterone gel in people with Prostatic Neoplasms and Hypogonadism, run by Canisius-Wilhelmina Hospital at 10 sites in Netherlands.
Trial summary
Sexual dysfunction is a common side effect of radical prostatectomy (RP) and has a significant negative impact on quality of life. With age the testosterone level in men declines; around 30% of men over 70 years of age meet the criteria of testosterone deficiency (TD). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasms, Hypogonadism, Testosterone Deficiency
- What is being tested?
- Testosterone gel
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 10 sitesNetherlands
- Study dates
- 12 Dec 2022to Dec 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men aged 18 years or older
- Histologically confirmed prostate cancer
- Radical prostatectomy performed as primary treatment
- At least one-sided nerve-sparing procedure performed
- Non-metastatic disease (cN0M0) based on the use of nomograms or imaging
- Undetectable PSA level (<0.1 µg/l or unmeasurable according to local protocol) within six weeks following RP
- A preoperative minimal sexual function, defined as a score of 40 points or more (out of 100) for the EPIC-26 sexual function domain
- Testosterone deficiency, defined as total testosterone <8 nmol/L, or total testosterone between 8-12 nmol/L with free testosterone <225 pmol/L, measured on two separate occasions, with normal or elevated luteinising hormone (LH)
Who cannot join
- Prior prostate cancer treatment, including but not limited to anti-hormonal therapy, radiotherapy, or brachytherapy (active surveillance allowed)
- Previous use of testosterone therapy for any reason
- Pathological stage pT3b or pT4 in the RP specimen
- Positive surgical margin(s) with ISUP grade 4 or 5 in the RP specimen
- Presence of metastatic lymph nodes if pelvic lymph node dissection was performed
- History of male breast cancer or liver tumour
Show all 11Show fewer
- Uncontrolled hypertension
- General contraindications for TRT
- Allergy for components in TRT agent or placebo
- Use of vitamin K antagonists
- Body mass index (BMI) >30 kg/m²
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
Netherlands10 sites, 10 recruiting
- Recruiting
Amsterdam UMC location VUmc
Amsterdam
André Vis, MD, PhD
- Recruiting
Netherlands Cancer Institute
Amsterdam
Pim van Leeuwen, MD, PhD
- Recruiting
Rijnstate
Arnhem
Carl Wijburg, MD, PhD
- Recruiting
Catharina Hospital
Eindhoven
Robert Hoekstra, MD
- Recruiting
Treant
Emmen
Luc Roelofs, MD, PhD
- Recruiting
Zuyderland
Heerlen
Max Bruins, MD, PhD
- Recruiting
St. Antonius Hospital
Nieuwegein
Harm van Melick, MD, PhD
- Recruiting
Canisius Wilhelmina Ziekenhuis
Nijmegen, 6532 SZ
Jean-Paul van Basten, MSc, PhD, +31024 365 82 55, j.vanbasten@cwz.nl
- Recruiting
Radboud university medical center
Nijmegen
Michiel Sedelaar, MD, PhD
- Recruiting
Máxima Medical Centre
Veldhoven
Alexander Bellaar Spruyt, MD
About this study
Sexual dysfunction is a common side effect of radical prostatectomy (RP) and has a significant negative impact on quality of life. With age the testosterone level in men declines; around 30% of men over 70 years of age meet the criteria of testosterone deficiency (TD). The negative impact of both TD and RP on sexual performance are likely to add up. The aim of this study is to assess the efficacy and safety of testosterone replacement therapy (TRT) on functional and oncological outcomes in testosterone deficient men following RP for prostate cancer (PCa).
Read the detailed description
Rationale: Radical prostatectomy (RP) is currently the most common treatment for non-metastatic prostate cancer (PCa). Two frequent side effects of this procedure are urinary incontinence and erectile dysfunction, both having a significant negative impact on quality of life.
Additionally, it is known that with age the testosterone level in men declines. This does not lead to symptoms in all men (asymptomatic testosterone deficiency). Both testosterone deficiency (TD) and radical prostatectomy are well-established to have a significant negative impact on sexual performance and are likely to add up in patients with a low testosterone following RP.
Objective: The aim of this study is to assess the effect of testosterone replacement therapy (TRT) on functional and oncological outcomes in testosterone deficient men following RP for PCa.
Study design: This study is a phase 3 prospective, randomized, placebo-controlled, single-blind clinical trial. Study population: All men over 18 years old diagnosed with non-metastatic prostate cancer who are scheduled for RP within three months as primary treatment, can be prescreened for inclusion. Prior to the RP, serum testosterone will be determined. Subsequently, within six weeks after the RP, serum testosterone will be determined again and patients will be screened for inclusion. If necessary, a third measurement of testosterone will be done. Eligible patients meet the criteria for TD and other inclusion criteria. Intervention: Patients will be randomized for testosterone replacement therapy (TRT) or placebo as a daily administered topical gel starting within 8 weeks after RP. Patients will receive TRT or placebo for one year following RP and will be monitored for another year for functional outcomes and for four more years to establish 5-year biochemical recurrence (BCR) free survival.
Main study parameters/endpoints:
The primary study endpoint is a clinically relevant (12 points or more) difference in the EPIC-26 domain for sexual functioning 12 months after RP in favor of testosterone deficient men receiving TRT compared with testosterone deficient men receiving placebo. Secondary endpoints include: urinary incontinence score, hormonal functioning score and BCR-free survival. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The number of visits and blood drawings are equal to standard of care follow-up after RP, with the exception of two or three extra blood samples at the first prescreening visit and within six weeks following RP. We ask patients to remain with their hospital for 24 months after RP for follow-up and to complete online questionnaires for the given visits. The five-year biochemical recurrence (BCR) free survival will be obtained through patient's medical records and if insufficient, through the Dutch Cancer Registry (NKR). Patients who receive TRT or placebo can experience local side-effects such as itching, rash and/or irritation at the site of application. In addition, patients who receive TRT can experience systemic sideeffects are gain of weight, hot flashes, acne and an increase in red blood count level. Furthermore, TRT might improve sexual functioning, urinary continence, hormonal functioning and BCR-free survival, but this is not certain and is subject of research in this study.
- Conditions
- Prostatic Neoplasms, Hypogonadism, Testosterone Deficiency
- Being tested
- Testosterone gel, Placebo
- Keywords
- Prostate cancer, Prostatectomy, Hypogonadism, Testosterone deficiency
- Medical subject headings
- Prostatic Neoplasms, Hypogonadism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Testosterone gelDrug
Also called Androgel
Topical gel containing testosterone
PlaceboDrug
Also called Placebo gel
Topical gel without active substance
| Study group | Role | What they receive |
|---|---|---|
| Testosterone therapy | Active comparator | Daily application of two pump auctions of 16.2mg/ml testosterone gel. Dosage may be altered depending on clinical response Receives: Drug: Testosterone gel |
| Placebo therapy | Placebo comparator | Daily application of two pump auctions of placebo gel. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinically relevant (≥12 points) difference in the EPIC-26 sexual functioning domain score, 12 months after radical prostatectomy between groups.
Functional recovery after radical prostatectomy will be assessed by EPIC-26 questionnaire, a Patient Reported Outcome Measure (PROM). Patients will be asked to complete this questionnaire online.
Measured: 12 months
Secondary outcomes (7)
Clinically relevant (≥12 points) difference in the EPIC-26 sexual functioning domain score 3 months after radical prostatectomy between groups.
Clinical relevance (>12 points) for sexual function domain score as measured by EPIC-26.
Measured: 3 months
Clinically relevant (≥12 points) difference in the EPIC-26 sexual functioning domain score 24 months after radical prostatectomy between groups.
Clinical relevance (>12 points) for sexual function domain score as measured by EPIC-26.
Measured: 24 months
Clinically relevant (≥9 points) difference in the EPIC-26 urinary incontinence domain score, 12 months after radical prostatectomy between groups.
Clinical relevance (>9 points) for Urinary incontinence domain score as measured by EPIC-26.
Measured: 12 months
Clinically relevant (≥9 points) difference in the EPIC-26 urinary incontinence domain score, 24 months after radical prostatectomy between groups.
Clinical relevance (>9 points) for Urinary incontinence domain score as measured by EPIC-26.
Measured: 24 months
Clinically relevant (≥6 points) difference in the EPIC-26 for hormonal functioning domain score, 12 months after radical prostatectomy between groups.
Clinical relevance (>6 points) for hormonal functioning domain score as measured by EPIC-26.
Measured: 12 months
Clinically relevant (≥6 points) difference in the EPIC-26 for hormonal functioning domain score, 24 months after radical prostatectomy between groups.
Clinical relevance (>6 points) for hormonal functioning domain score as measured by EPIC-26.
Measured: 24 months
Difference in biochemical recurrence rate between groups.
Biochemical recurrence (BCR) is defined as the occurrence of measurable (>0.1 ng/ml) prostate specific antigen (PSA), during routinely follow-up up to five years after surgery, determined at two different occasions with at least one week between them.The BCR-rate between the placebo and control group will be compared to determine the influence of testosterone therapy on BCR.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2021
- Study start12 Dec 2022
- Primary completionDec 2027 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Canisius-Wilhelmina Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Besins Healthcare
- Responsible party
- Sponsor
- Investigators
- Diederik Somford, MD, PhD, Principal investigator, Canisius-Wilhelmina Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04833426
- Sponsor's protocol ID
- NL7436209120
- Other IDs
- 2020-003012-27, 2020-6874
- Acronym
- ENFORCE
- Status last verified
- May 2025
- First submitted
- 5 Feb 2021
- Last updated
- 2 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Baas D, van Drumpt J, Kiemeney L, Beck J, Ostergren PB, Sedelaar M, Hoekstra R, Spruyt AB, van Melick H, Bruins M, van Leeuwen P, Vis A, Wijburg C, Roelofs L, van den Bergh R, van Soest R, van Basten JP, Somford D. Impact of Testosterone Replacement Therapy on Functional and Oncological Outcomes Following Radical Prostatectomy (ENFORCE Study). Eur Urol Oncol. 2026 Apr;9(2):479-486. doi: 10.1016/j.euo.2025.05.024. Epub 2025 Jun 12.
PubMed 40514343
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Peri-operative tEstosterone Levels on oNcological and Functional Outcomes in RadiCal prostatEctomy
- ClinicalTrials.gov ID
- NCT04833426
- Acronym / sponsor ID
- ENFORCE / NL7436209120
- Conditions
- Prostatic Neoplasms, Hypogonadism, Testosterone Deficiency
- Keywords
- Prostate cancer, Prostatectomy, Hypogonadism, Testosterone deficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Canisius-Wilhelmina HospitalUniversity, hospital or other
- Collaborators
- Besins Healthcare
- Study start
- 12 Dec 2022 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 6 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sexual dysfunction is a common side effect of radical prostatectomy (RP) and has a significant negative impact on quality of life. With age the testosterone level in men declines; around 30% of men over 70 years of age meet the criteria of testosterone deficiency (TD). The negative impact of both TD and RP on sexual performance are likely to add up. The aim of this study is to assess the efficacy and safety of testosterone replacement therapy (TRT) on functional and oncological outcomes in testosterone deficient men following RP for prostate cancer (PCa).
Detailed description
Rationale: Radical prostatectomy (RP) is currently the most common treatment for non-metastatic prostate cancer (PCa). Two frequent side effects of this procedure are urinary incontinence and erectile dysfunction, both having a significant negative impact on quality of life.
Additionally, it is known that with age the testosterone level in men declines. This does not lead to symptoms in all men (asymptomatic testosterone deficiency). Both testosterone deficiency (TD) and radical prostatectomy are well-established to have a significant negative impact on sexual performance and are likely to add up in patients with a low testosterone following RP.
Objective: The aim of this study is to assess the effect of testosterone replacement therapy (TRT) on functional and oncological outcomes in testosterone deficient men following RP for PCa.
Study design: This study is a phase 3 prospective, randomized, placebo-controlled, single-blind clinical trial. Study population: All men over 18 years old diagnosed with non-metastatic prostate cancer who are scheduled for RP within three months as primary treatment, can be prescreened for inclusion. Prior to the RP, serum testosterone will be determined. Subsequently, within six weeks after the RP, serum testosterone will be determined again and patients will be screened for inclusion. If necessary, a third measurement of testosterone will be done. Eligible patients meet the criteria for TD and other inclusion criteria. Intervention: Patients will be randomized for testosterone replacement therapy (TRT) or placebo as a daily administered topical gel starting within 8 weeks after RP. Patients will receive TRT or placebo for one year following RP and will be monitored for another year for functional outcomes and for four more years to establish 5-year biochemical recurrence (BCR) free survival.
Main study parameters/endpoints:
The primary study endpoint is a clinically relevant (12 points or more) difference in the EPIC-26 domain for sexual functioning 12 months after RP in favor of testosterone deficient men receiving TRT compared with testosterone deficient men receiving placebo. Secondary endpoints include: urinary incontinence score, hormonal functioning score and BCR-free survival. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The number of visits and blood drawings are equal to standard of care follow-up after RP, with the exception of two or three extra blood samples at the first prescreening visit and within six weeks following RP. We ask patients to remain with their hospital for 24 months after RP for follow-up and to complete online questionnaires for the given visits. The five-year biochemical recurrence (BCR) free survival will be obtained through patient's medical records and if insufficient, through the Dutch Cancer Registry (NKR). Patients who receive TRT or placebo can experience local side-effects such as itching, rash and/or irritation at the site of application. In addition, patients who receive TRT can experience systemic sideeffects are gain of weight, hot flashes, acne and an increase in red blood count level. Furthermore, TRT might improve sexual functioning, urinary continence, hormonal functioning and BCR-free survival, but this is not certain and is subject of research in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Testosterone therapy | Active comparator | Drug: Testosterone gelDaily application of two pump auctions of 16.2mg/ml testosterone gel. Dosage may be altered depending on clinical response |
| Placebo therapy | Placebo comparator | Drug: PlaceboDaily application of two pump auctions of placebo gel. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Men aged 18 years or older
- Histologically confirmed prostate cancer
- Radical prostatectomy performed as primary treatment
- At least one-sided nerve-sparing procedure performed
- Non-metastatic disease (cN0M0) based on the use of nomograms or imaging
Key exclusion criteria (11 listed)
- Prior prostate cancer treatment, including but not limited to anti-hormonal therapy, radiotherapy, or brachytherapy (active surveillance allowed)
- Previous use of testosterone therapy for any reason
- Pathological stage pT3b or pT4 in the RP specimen
- Positive surgical margin(s) with ISUP grade 4 or 5 in the RP specimen
- Presence of metastatic lymph nodes if pelvic lymph node dissection was performed
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Testosterone gelAlso: AndrogelTopical gel containing testosterone | Drug | Testosterone therapy |
| PlaceboAlso: Placebo gelTopical gel without active substance | Drug | Placebo therapy |
Primary outcome
Clinically relevant (≥12 points) difference in the EPIC-26 sexual functioning domain score, 12 months after radical prostatectomy between groups.
Time frame: 12 months
Functional recovery after radical prostatectomy will be assessed by EPIC-26 questionnaire, a Patient Reported Outcome Measure (PROM). Patients will be asked to complete this questionnaire online.
7 secondary outcomes
Clinically relevant (≥12 points) difference in the EPIC-26 sexual functioning domain score 3 months after radical prostatectomy between groups.
Time frame: 3 months
Clinically relevant (≥12 points) difference in the EPIC-26 sexual functioning domain score 24 months after radical prostatectomy between groups.
Time frame: 24 months
Clinically relevant (≥9 points) difference in the EPIC-26 urinary incontinence domain score, 12 months after radical prostatectomy between groups.
Time frame: 12 months
Clinically relevant (≥9 points) difference in the EPIC-26 urinary incontinence domain score, 24 months after radical prostatectomy between groups.
Time frame: 24 months
Clinically relevant (≥6 points) difference in the EPIC-26 for hormonal functioning domain score, 12 months after radical prostatectomy between groups.
Time frame: 12 months
Clinically relevant (≥6 points) difference in the EPIC-26 for hormonal functioning domain score, 24 months after radical prostatectomy between groups.
Time frame: 24 months
Difference in biochemical recurrence rate between groups.
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2025.
- Derived from this study: PubMed 40514343Baas D, van Drumpt J, Kiemeney L, Beck J, Ostergren PB, Sedelaar M, Hoekstra R, Spruyt AB, van Melick H, Bruins M, van Leeuwen P, Vis A, Wijburg C, Roelofs L, van den Bergh R, van Soest R, van Basten JP, Somford D. Impact of Testosterone Replacement Therapy on Functional and Oncological Outcomes Following Radical Prostatectomy (ENFORCE Study). Eur Urol Oncol. 2026 Apr;9(2):479-486. doi: 10.1016/j.euo.2025.05.024. Epub 2025 Jun 12.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Diederik Somford, MD, PhD principal investigator
Canisius-Wilhelmina Hospital
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Testosterone gel in people with Prostatic Neoplasms and Hypogonadism, run by Canisius-Wilhelmina Hospital at 10 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joost van Drumpt, MSc (+31243658190, enforce@cwz.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinically relevant (≥12 points) difference in the EPIC-26 sexual functioning domain score, 12 months after radical prostatectomy between groups. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04833426, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2025; AzTrials last refreshed its copy on 7 Nov 2026.