Improving Quality of Life of Prostate Cancer Survivors With Androgen Deficiency

The purpose of this phase II trial is to determine the efficacy and safety of testosterone replacement therapy (TRT) in improving the symptoms of androgen deficiency and health-related quality of life in men with prostate cancer who have undergone radical prostatectomy.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Testosterone Cypionate 100 MG/ML; Drug: Placebo

Detailed Description

The overall objective is to conduct a proof-of-concept double-blind, placebo-controlled, parallel group, randomized trial to determine the efficacy and safety of testosterone replacement therapy (TRT) in improving the symptoms of androgen deficiency (sexual symptoms, low energy, and physical dysfunction) and overall health-related quality of life in men with prostate cancer who have undergone radical prostatectomy for organ-localized disease (pT2,N0,M0), Gleason score < 7 (3+4), who have undetectable PSA (<0.1 ng/mL using a sensitive PSA assay) for > 2 years after radical prostatectomy, and who have androgen deficiency.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Men with prostate cancer, who have Stage pT2, N0, M0 lesions (confined to the gland); Combined Gleason score of 7 (3+4 elements) or less; Preoperative PSA less than 10 ng/ml; Stable and undetectable PSA level (PSA less than 0.1 ng/mL using an assay that has a functional sensitivity of 0.1 ng/mL) for at least two years after radical prostatectomy.

• Age: 40 years and older
• Presence of symptoms related to sexual dysfunction, fatigue/low vitality, or physical dysfunction.
• An average of two fasting, early morning serum testosterone levels, measured by LC-MS/MS, less than 275 mg/dL and/or free testosterone by equilibrium dialysis <60 pg/mL. middle-aged and older men with mean testosterone levels > 300 ng/dL.
• Ability and willingness to provide informed consent

Exclusion Criteria:

• Men who have undergone radiation therapy
• Men receiving androgen deprivation therapy will be excluded.
• Hemoglobin <10 g/dL or >16.5 g/dL
• Severe untreated sleep apnea
• Allergy to sesame oil
• Uncontrolled heart failure
• Myocardial infarction, acute coronary syndrome, revascularization surgery, or stroke within 3 months
• Serum creatinine >2.5 mg/dL; ALT 3x upper limit of normal;
• Hemoglobin A1c >7.5% or diabetes requiring insulin therapy
• Body mass index (BMI) >40 kg/m2
• Untreated depression. Subjects with depression who have been on stable anti-depressant medication, or undergoing CBT for more than three months are eligible.
• Men with axis I psychiatric disorder, such as schizophrenia, will be excluded.
• Subjects who have used the following medications within the past 6 months: testosterone, DHEA, estrogens, GnRH analogs, antiandrogens, spironolactone, ketoconazole, rhGH, megestrol acetate, prednisone 20 mg daily or equivalent doses of other glucocorticoids for more than two weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment Arm; Weekly IM administration of 100 mg testosterone cypionate for 12 weeks.	Drug: Testosterone Cypionate 100 MG/ML; 100 mg testosterone cypionate administered by intramuscular injection weekly for 12 weeks.; Other Names: Depo-Testosterone
Placebo Comparator: Control Arm; Weekly IM administration of placebo for 12 weeks.	Drug: Placebo; Placebo administered by intramuscular injection weekly for 12 weeks.; Other Names: Inactive comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Biochemical Recurrence of Prostate Cancer	The primary safety endpoint is the number of participants with biochemical recurrence of prostate cancer. Biochemical recurrence is defined as two or more consecutive serum PSA levels of 0.2 ng/mL or higher.	the 12-week treatment and the 3-month follow-up
Change From Baseline in Overall Sexual Activity, Assessed Using Psychosexual Diary Questionnaire (PDQ) Question 4	The primary efficacy endpoint is the change from baseline in overall sexual activity, assessed using Psychosexual Diary Questionnaire (PDQ) Question 4. Subjects complete the PDQ questionnaire daily for 7 consecutive days before each visit. The PDQ covers 3 domains:1) sexual desire, enjoyment, and performance; 2) sexual activity score; and 3) mood. Sexual activity (PDQ-4) is assessed using a checklist of 12 sexual activities including sexual interactions, masturbation, intercourse, erection, orgasm, and ejaculation on each of the 7 days. The value is recorded as 0 (none) or 1 (any) for each of the sexual activities. Weekly value is the sum of "any" responses for the week. The sexual activity score is the average of the weekly values. The score ranges from 0 to 12, with 0 indicating no activity had taken place that week and with higher values indicating more sexual activity.	Week 6, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PSA	The secondary safety endpoint is change in PSA levels. Change from baseline in PSA could not be computed because the majority of the participants had undetectable PSA levels at baseline and post-baseline. Here, the number of participants with various PSA levels is reported.	Week 12
Change From Baseline in Lower Urinary Tract Symptoms, Ascertained Using the International Prostate Symptom Score (IPSS)	The secondary safety endpoint is the change from baseline in lower urinary tract symptoms, ascertained using the International Prostate Symptom Score (IPSS). The IPSS is a validated 8-question survey (7 symptom questions, 1 quality-of-life question) used to assess the severity of lower urinary tract symptoms (LUTS) associated with BPH, ranging from 0-35, with a higher score indicating a more severe negative symptoms.	Week 6, Week 12
Change From Baseline in Hemoglobin	The secondary safety endpoint is the change from baseline in hemoglobin levels.	Week 6, Week 12
Change From Baseline in Hematocrit	The secondary safety endpoint is the change from baseline in hematocrit levels.	Week 6, Week 12
Number of Participants With Erythrocytosis in the Two Study Arms	The secondary safety endpoint is the number of participants with erythrocytosis (confirmed hemoglobin > 18.0 g/dL) in the two study arms.	Week 12
Number of Participants With Clinical Prostate Cancer Recurrence in the Two Study Arms	The secondary safety endpoint is the number of participants with clinical prostate cancer recurrence in the two study arms.	Week 12
Change From Baseline in Sexual Desire, Assessed by the DeRogatis Inventory of Sexual Function Sexual Desire (DISF-SD) Questionnaire	The secondary efficacy endpoint is sexual desire, assessed by the DeRogatis Inventory of Sexual Function Sexual Desire (DISF-SD) Questionnaire. The DISF evaluates an individual's sexual health across five primary domains: sexual cognition/fantasy, arousal, behavior/experience, orgasm, and sexual drive/relationship. The Sexual Desire (SD) subset assesses an individual's subjective libido and frequency of sexual drive. The Sexual Desire score can range from 0 to 33, with a higher score indicating more sexual desire.	Week 6, Week 12
Change in Erectile Function Assessed by the International Index of Erectile Function (IIEF) Questionnaire.	The secondary efficacy endpoint is erectile function will be assessed by the International Index of Erectile Function (IIEF) Questionnaire. The IIEF is a 15-item questionnaire that covers 4 domains of sexual function: erectile function, sexual desire, orgasmic function, and intercourse satisfaction. Each question has a potential score of 0 to 5 for a maximal score of 75 for the entire scale. Our focus in this study is on erectile function domain score, which can range from 0 to 30, lower scores indicating poor erectile function, and higher score indicating better erectile function.	Week 6, Week 12
Change in Energy Level, Assessed Using the Hypogonadism Energy Diary (HED)	The secondary efficacy endpoint is energy level, assessed using the Hypogonadism Energy Diary (HED). The total HED scale score is the sum of each of the six item weekly scores, with higher scores corresponding to greater energy level. The HED total score is linearly transformed to a scale of 0-100. Lower scores indicate lower energy (or more tiredness) and higher scores indicate more energy (less tiredness).	Week 6, Week 12
Change in Mood, Assessed by the Positive and Negative Affect Schedule (PANAS)	Mood and well-being will be assessed by the Positive and Negative Affect Schedule (PANAS). The PANAS is a 20-item self-report measure to assess positive affect (PA) and negative affect (NA), with scores ranging from 10 to 50 for both the PA score and the NA score. For the PA score (10-50), higher scores represent higher levels of positive emotions, engagement, and enthusiasm. For the NA score (10-50), higher scores indicate higher levels of negative engagement, distress, and anxiety.	Week 6, Week 12
Change From Baseline in Prostate Cancer-related Quality of Life, Measured Using the Hormonal and Sexual Domains of the Expanded Prostate Cancer Index Composite (EPIC)	The secondary efficacy endpoint is change from baseline in prostate cancer-related quality of life measured using the hormonal and sexual domains of the Expanded Prostate Cancer Index Composite (EPIC). Expanded Prostate Cancer Index Composite Instrument (EPIC-26) for Measuring Health-Related Quality of Life Among Prostate Cancer Survivors EPIC QOL is a 26-item questionnaire that assesses quality of life in 5 domains: urinary incontinence, urinary irritation/obstruction, bowel, sexual and vitality/hormonal domain scores. All domains for EPIC-26 are reported on a 0 to 100 score, with higher scores representing favorable Health-Related Quality of Life (HRQOL).	Week 6, Week 12
Change From Baseline in Self-reported Physical Function, Assessed Using the Physical Function Component of MOS SF-36 (PF10)	The secondary efficacy endpoint is change from baseline self-reported physical function, assessed using the physical function component of MOS SF-36 (PF10). The PF-10 (Physical Functioning Scale) is the 10-item subscale within the MOS SF-36 assessing the extent to which health limits physical activities, such as self-care, walking, and lifting. Scores range from 0 to 100, where higher numbers mean better physical function and fewer limitations.	Week 6, Week 12
Change From Baseline in Performance-based Physical Function, Assessed by Measuring Loaded Stair Climbing Power	The secondary efficacy endpoint is change from baseline in performance-based physical function, assessed by measuring loaded stair climbing power.	Week 12
Change From Baseline in Chest Press Strength	The secondary efficacy endpoint is the change from baseline in Chest Press Max weight	Week 12
Change From Baseline in Leg Press Strength	The secondary efficacy endpoint is the change from baseline in Leg Press Max weight	Week 12
Change in Aerobic Capacity (VO2peak) Achieved During Cardiopulmonary Exercise Testing	The secondary efficacy endpoint is aerobic capacity (VO2peak) achieved during cardiopulmonary exercise testing.	Week 12
Change in Lean Body Mass	Change from baseline in whole body, appendicular, and trunk lean tissue mass measured using dual energy X-ray absorptiometry (DXA).	Week 12
Change in Fat Body Mass	Change from baseline in whole body, appendicular, and trunk fat tissue mass measured using dual energy X-ray absorptiometry (DXA).	Week 12

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Shalender Bhasin, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Bhasin S, Burnett AL, Gagliano-Juca T, Storer TW, Reid KF, Shang YV, Privat F, Chandra MS, Weiss M, Memish-Beleva Y, Lam H, Kibel AS, Pencina KM. Testosterone Treatment in Prostate Cancer Survivors With Hypogonadism: A Randomized Clinical Trial. JAMA Intern Med. 2026 Jul 1;186(7):805-814. doi: 10.1001/jamainternmed.2026.1343.
• Sentana-Lledo D, Saraf A, Morgans AK. Symptom Burden and Survivorship Care for Patients With Prostate Cancer on Androgen Deprivation Therapy. J Natl Compr Canc Netw. 2024 Dec 20;23(1):e247047. doi: 10.6004/jnccn.2024.7047.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2019
• Primary Completion (Actual): May 16, 2025
• Study Completion (Actual): July 16, 2025

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: October 22, 2018
• First Posted (Actual): October 23, 2018

Study Record Updates

• Last Update Posted (Actual): July 16, 2026
• Last Update Submitted That Met QC Criteria: June 18, 2026
• Last Verified: January 1, 2025

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; Antineoplastic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anabolic Agents; Androgens; testosterone 17 beta-cypionate
• Other Study ID Numbers: 18-733; 5R01AG060539-05 (U.S. NIH Grant/Contract)

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.: No