Testosterone Replacement Therapy for the Treatment of Low Testosterone in Hypogonadal Men With Localized Prostate Cancer on Active Surveillance

Investigating the Effect of Testosterone Replacement Therapy Among Hypogonadal Men With Localized Prostate Cancer on Active Surveillance

This phase IV trial studies the effects of testosterone replacement therapy (TRT) on treatment outcomes in hypogonadal men with prostate cancer that has not spread to other parts of the body (localized) and who are on active surveillance (AS). AS in prostate cancer involves closely watching the patient's condition through regular physical exams and blood tests, but not giving treatment unless there are changes in test results. It can be a practical alternative to treatment in localized prostate cancer. Hypogonadal men have low testosterone associated with symptoms such as low libido and erectile problems. TRT can be used to treat hypogonadism by increasing testosterone levels, which may improve associated symptoms. TRT is often not used in men with prostate cancer due to concerns it may lead to the cancer growing or spreading. This may lead hypogonadal men to have a poor quality of life or to discontinue AS. TRT may improve treatment and quality of life outcomes in hypogonadal men with localized prostate cancer on active surveillance.

Study Overview

• Status: Recruiting
• Conditions: Localized Prostate Carcinoma; Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage III Prostate Cancer AJCC v8
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Biopsy of Prostate; Other: Patient Observation; Drug: Therapeutic Testosterone

Detailed Description

PRIMARY OBJECTIVES:

I. To investigate the impact of TRT on Gleason grade progression in hypogonadal men with localized prostate cancer on active surveillance, and the association between TRT and the likelihood of discontinuation of active surveillance in the same population.

II. To assess the impact of TRT on the quality of life, including changes in the International Prostate Symptom Score (IPSS) and the association with sexual health measured by the Sexual Health Inventory for Men (SHIM), in hypogonadal men with localized prostate cancer on active surveillance.

SECONDARY OBJECTIVES:

I. To examine the influence of TRT on radiographic progression in hypogonadal men with localized prostate cancer on active surveillance, by assessing changes in the size of abnormal magnetic resonance imaging (MRI) lesions.

II. To evaluate the association between TRT and biochemical progression by analyzing changes in prostate-specific antigen (PSA) levels over time in the studied population.

III. To systematically monitor and document TRT-related adverse events and complications, and concurrently assess the association between TRT and the likelihood of discontinuation due to adverse events in the studied population.

OUTLINE: Patients are assigned to 1 of 3 groups.

GROUP 1: Patients with normal testosterone level undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.

GROUP 2: Patients with low testosterone level associated with hypogonadal symptoms and willing to receive TRT receive testosterone per treating physician discretion via injection, gel, lotion, or transdermal patch and undergo standard AS for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.

GROUP 3: Patients with low testosterone level with no symptoms, or low testosterone level associated with hypogonadal symptoms but declined TRT undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
      • Contact: Ahmed Aly; Phone Number: 716-845-6844; Email: ahmed.aly@roswellpark.org
      • Principal Investigator: Ahmed Aly

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men aged ≥ 18 years
• Men with localized prostate cancer are eligible for active surveillance (National Comprehensive Cancer Network [NCCN] very low, low, and intermediate favorable risk group)
• Participant must understand the investigational nature of this study and sign an independent ethics committee/institutional review board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Patients with NCCN intermediate unfavorable, high risk, or very high-risk localized prostate cancer

• For men being considered for Group 2 (TRT), Patients with contraindications to TRT, which include,

  • Locally advanced or metastatic prostate cancer
  • Male breast cancer
  • Men with an active desire to have children
  • Hematocrit levels > 54% or baseline hematocrit of 48-50%
  • Uncontrolled or poorly controlled congestive heart failure
  • IPSS (International Prostate Symptom Score) score > 19
  • Family history of venous thromboembolism
• Unwilling or unable to follow protocol requirements
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1 (AS); Patients with normal testosterone level undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.	Other: Questionnaire Administration; Ancillary studies; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Biopsy of Prostate; Undergo prostate biopsy; Other Names: Prostate Biopsy; Prostatic Biopsy; Other: Patient Observation; Undergo standard AS; Other Names: Observation; Active Surveillance; deferred therapy; expectant management; Watchful Waiting
Experimental: Group 2 (TRT, AS); Patients with low testosterone level associated with hypogonadal symptoms and willing to receive TRT receive testosterone per treating physician discretion via injection, gel, lotion, or transdermal patch and undergo standard AS for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.	Other: Questionnaire Administration; Ancillary studies; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Biopsy of Prostate; Undergo prostate biopsy; Other Names: Prostate Biopsy; Prostatic Biopsy; Other: Patient Observation; Undergo standard AS; Other Names: Observation; Active Surveillance; deferred therapy; expectant management; Watchful Waiting; Drug: Therapeutic Testosterone; Given via injection, gel, lotion, or transdermal patch; Other Names: Testosterone; Mertestate; Testoderm; Testolin; Testostroval; Testostroval-PA; Testro AQ; Trans-Testosterone; Virosterone
Active Comparator: Group 3 (AS); Patients with low testosterone level with no symptoms, or low testosterone level associated with hypogonadal symptoms but declined TRT undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.	Other: Questionnaire Administration; Ancillary studies; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Biopsy of Prostate; Undergo prostate biopsy; Other Names: Prostate Biopsy; Prostatic Biopsy; Other: Patient Observation; Undergo standard AS; Other Names: Observation; Active Surveillance; deferred therapy; expectant management; Watchful Waiting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gleason grade progression	The Gleason grade progression will be summarized by group using standard Kaplan-Meier methods, where estimates of the median or specified rates will be obtained. Comparisons will be made between groups using the log-rank test. As exploratory analyses, Cox regression models may be considered to adjust for relevant demographic or clinical confounders. The Bonferroni method will be used to control the family-wise error rate at 0.10.	From start of active surveillance until any progression in primary, secondary, or a combination of Gleason grades, definitive treatment, or last follow-up, assessed up to 5 years
Discontinuation of active surveillance	The discontinuation of active surveillance will be summarized by group using standard Kaplan-Meier methods, where estimates of the median or specified rates will be obtained. Comparisons will be made between groups using the log-rank test. As exploratory analyses, Cox regression models may be considered to adjust for relevant demographic or clinical confounders. The Bonferroni method will be used to control the family-wise error rate at 0.10.	From start of active surveillance until discontinuation of active surveillance due to any cause or last follow-up, assessed up to 5 years
International Prostate Symptom Score (Quality-of-life)	Will be modeled as a function of group, timepoint, their two-way interaction, and a random subject effect using linear mixed models. Tests about the appropriate contrasts of model estimates will be used to compare mean changes in quality of life between groups at specified timepoints. All model assumptions will be verified graphically, and transformations applied as appropriate. As exploratory analyses, additional models may be considered to adjust for relevant demographic or clinical confounders. The Bonferroni method will be used to control the family-wise error rate at 0.10.	Up to 5 years
Sexual Health Inventory for Men score (Quality-of-life)	Will be modeled as a function of group, timepoint, their two-way interaction, and a random subject effect using linear mixed models. Tests about the appropriate contrasts of model estimates will be used to compare mean changes in quality of life between groups at specified timepoints. All model assumptions will be verified graphically, and transformations applied as appropriate. As exploratory analyses, additional models may be considered to adjust for relevant demographic or clinical confounders. The Bonferroni method will be used to control the family-wise error rate at 0.10.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic progression	Will assess change in the size of abnormal magnetic resonance imaging (MRI) lesions, if any. Will utilize the PRECISE scoring system, which considers factors such as changes in lesion volume or appearance on MRI and can provide a standardized and objective method for assessing progression. Will be summarized by group using standard Kaplan-Meier methods, where estimates of the median or specified rates will be obtained. Comparisons will be made between groups using the log-rank test.	From start of active surveillance until radiographic progression, definitive treatment, or last follow-up, assessed up to 5 years
Biochemical progression	Will be assessed by change in the PSA over time. Will be summarized by group using standard Kaplan-Meier methods, where estimates of the median or specified rates will be obtained. Comparisons will be made between groups using the log-rank test.	From the start of active surveillance until prostate specific antigen (PSA) progression, definitive treatment, or last follow-up, assessed up to 5 years
Incidence of testosterone replacement therapy (TRT)-related adverse events	Will be assessed in Group 2 patients. Will be summarized by attribution and grade using frequencies and relative frequencies.	Up to 5 years
Incidence of TRT-related complications	Will be assessed in Group 2 patients. Will be summarized by attribution and grade using frequencies and relative frequencies.	Up to 5 years
TRT discontinuation	Will be assessed in Group 2 patients.	Up to 5 years

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Ahmed Aly, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2025
• Primary Completion (Estimated): January 15, 2029
• Study Completion (Estimated): January 15, 2029

Study Registration Dates

• First Submitted: December 10, 2024
• First Submitted That Met QC Criteria: December 10, 2024
• First Posted (Actual): December 13, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Health Services Administration; Investigative Techniques; Methods; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Quality of Health Care; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Chemistry Techniques, Analytical; Spectrum Analysis; Gonadal Steroid Hormones; Gonadal Hormones; Androstenes; Androstanes; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Androstenols; Testosterone Congeners; Testosterone; Observation; Specimen Handling; Magnetic Resonance Spectroscopy; Watchful Waiting; Testosterone Propionate
• Other Study ID Numbers: I-3920923 (Other Identifier: Roswell Park Cancer Institute); NCI-2024-09551 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes