ENFORCE: Impact of Peri-operative tEstosterone Levels on oNcological and Functional Outcomes in RadiCal prostatEctomy

Sponsor

Canisius-Wilhelmina Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04833426

Collaborator

Besins Healthcare (Industry)

140

Enrollment

Locations

Arms

Anticipated Duration (Months)

23.3

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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). 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).

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms Hypogonadism Testosterone Deficiency	Drug: Testosterone gel Drug: Placebo	Phase 3

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

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Impact of Peri-operative tEstosterone Levels on oNcological and Functional Outcomes in RadiCal prostatEctomy

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Apr 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Testosterone therapy Daily application of two pump auctions of 16.2mg/ml testosterone gel. Dosage may be altered depending on clinical response	Drug: Testosterone gel Topical gel containing testosterone
Placebo Comparator: Placebo therapy Daily application of two pump auctions of placebo gel.	Drug: Placebo Topical gel without active substance Other Names: Placebo gel

Arm

Intervention/Treatment

Active Comparator: Testosterone therapy

Daily application of two pump auctions of 16.2mg/ml testosterone gel. Dosage may be altered depending on clinical response

Drug: Testosterone gel

Topical gel containing testosterone

Placebo Comparator: Placebo therapy

Daily application of two pump auctions of placebo gel.

Drug: Placebo

Topical gel without active substance

Other Names:

Placebo gel

Outcome Measures

Primary Outcome Measures

Clinically relevant (≥12 points) difference in the EPIC-26 sexual functioning domain score, 12 months after radical prostatectomy between groups. [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.

Secondary Outcome Measures

Clinically relevant (≥12 points) difference in the EPIC-26 sexual functioning domain score 3 months after radical prostatectomy between groups. [3 months]
Clinical relevance (>12 points) for sexual function domain score as measured by EPIC-26.
Clinically relevant (≥12 points) difference in the EPIC-26 sexual functioning domain score 24 months after radical prostatectomy between groups. [24 months]
Clinical relevance (>12 points) for sexual function domain score as measured by EPIC-26.
Clinically relevant (≥9 points) difference in the EPIC-26 urinary incontinence domain score, 12 months after radical prostatectomy between groups. [12 months]
Clinical relevance (>9 points) for Urinary incontinence domain score as measured by EPIC-26.
Clinically relevant (≥9 points) difference in the EPIC-26 urinary incontinence domain score, 24 months after radical prostatectomy between groups. [24 months]
Clinical relevance (>9 points) for Urinary incontinence domain score as measured by EPIC-26.
Clinically relevant (≥6 points) difference in the EPIC-26 for hormonal functioning domain score, 12 months after radical prostatectomy between groups. [12 months]
Clinical relevance (>6 points) for hormonal functioning domain score as measured by EPIC-26.
Clinically relevant (≥6 points) difference in the EPIC-26 for hormonal functioning domain score, 24 months after radical prostatectomy between groups. [24 months]
Clinical relevance (>6 points) for hormonal functioning domain score as measured by EPIC-26.
Difference in biochemical recurrence rate between groups. [5 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Unmeasurable PSA after RP
pT2-pT3a after RP
ISUP 1-3 regardless of surgical margins
ISUP 4-5 with negative surgical margins
At least one-sided nerve-sparing procedure
Baseline score sexual functioning domain of ≥ 40 points (EPIC-26)

Exclusion Criteria:

Metastatic disease (cN1/M1)
pT3b or pT4 after RP
Prior treatment for PCa
Prior TRT
Medical history of male breast- or liver carcinoma
Uncontrolled hypertension
General contra-indication for TRT
Allergy for components in TRT
Use of vitamin K-antagonists
BMI > 30

Contacts and Locations

Locations

	Site	City	Country
1	Jeroen Bosch Hospital	's-Hertogenbosch	Netherlands
2	Netherlands Cancer Institute	Amsterdam	Netherlands
3	Catharina Hospital	Eindhoven	Netherlands
4	Zuyderland	Heerlen	Netherlands
5	St. Antonius Hospital	Nieuwegein	Netherlands
6	Radboud university medical center	Nijmegen	Netherlands