Prostate Cancer
Conditions
Brief summary
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.
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.
Interventions
100 mg testosterone cypionate administered by intramuscular injection weekly for 12 weeks.
DRUGPlacebo
Placebo administered by intramuscular injection weekly for 12 weeks.
Sponsors
Dana-Farber Cancer Institute
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Biochemical Recurrence of Prostate Cancer | the 12-week treatment and the 3-month follow-up | 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. |
| Change From Baseline in Overall Sexual Activity, Assessed Using Psychosexual Diary Questionnaire (PDQ) Question 4 | Week 6, Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in PSA | Week 12 | 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. |
| Change From Baseline in Lower Urinary Tract Symptoms, Ascertained Using the International Prostate Symptom Score (IPSS) | Week 6, Week 12 | 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. |
| Change From Baseline in Hemoglobin | Week 6, Week 12 | The secondary safety endpoint is the change from baseline in hemoglobin levels. |
| Change From Baseline in Hematocrit | Week 6, Week 12 | The secondary safety endpoint is the change from baseline in hematocrit levels. |
| Number of Participants With Erythrocytosis in the Two Study Arms | Week 12 | The secondary safety endpoint is the number of participants with erythrocytosis (confirmed hemoglobin \> 18.0 g/dL) in the two study arms. |
| Number of Participants With Clinical Prostate Cancer Recurrence in the Two Study Arms | Week 12 | The secondary safety endpoint is the number of participants with clinical prostate cancer recurrence in the two study arms. |
| Change From Baseline in Sexual Desire, Assessed by the DeRogatis Inventory of Sexual Function Sexual Desire (DISF-SD) Questionnaire | Week 6, Week 12 | 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. |
| Change in Erectile Function Assessed by the International Index of Erectile Function (IIEF) Questionnaire. | Week 6, Week 12 | 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. |
| Change in Energy Level, Assessed Using the Hypogonadism Energy Diary (HED) | Week 6, Week 12 | 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). |
| Change in Mood, Assessed by the Positive and Negative Affect Schedule (PANAS) | Week 6, Week 12 | 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. |
| 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) | Week 6, Week 12 | 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). |
| Change From Baseline in Self-reported Physical Function, Assessed Using the Physical Function Component of MOS SF-36 (PF10) | Week 6, Week 12 | 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. |
| Change From Baseline in Performance-based Physical Function, Assessed by Measuring Loaded Stair Climbing Power | Week 12 | The secondary efficacy endpoint is change from baseline in performance-based physical function, assessed by measuring loaded stair climbing power. |
| Change From Baseline in Chest Press Strength | Week 12 | The secondary efficacy endpoint is the change from baseline in Chest Press Max weight |
| Change From Baseline in Leg Press Strength | Week 12 | The secondary efficacy endpoint is the change from baseline in Leg Press Max weight |
| Change in Aerobic Capacity (VO2peak) Achieved During Cardiopulmonary Exercise Testing | Week 12 | The secondary efficacy endpoint is aerobic capacity (VO2peak) achieved during cardiopulmonary exercise testing. |
| Change in Lean Body Mass | Week 12 | Change from baseline in whole body, appendicular, and trunk lean tissue mass measured using dual energy X-ray absorptiometry (DXA). |
| Change in Fat Body Mass | Week 12 | Change from baseline in whole body, appendicular, and trunk fat tissue mass measured using dual energy X-ray absorptiometry (DXA). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORShalender Bhasin, MD
Brigham and Women's Hospital
Participant flow
Pre-assignment details
We initially planned to enroll 71 men per arm for a total of 142 men. As the study progressed, the loss-to-follow rates were substantially lower. Accordingly, with the concurrence of the trial's Data and Safety Monitoring Board (DSMB) and the NIA program staff, the target sample size was revised to 134 subjects as planned enrollment anticipating that it will still provide the same statistical power as originally assumed. In the end,136 subjects were enrolled and randomized.
Baseline characteristics
| Characteristic | — |
|---|---|
| Aerobic Capacity (VO2peak) Achieved During Cardiopulmonary Exercise Testing | 1.9 L/min STANDARD_DEVIATION 0.5 |
| Age, Continuous | 68.6 Years STANDARD_DEVIATION 6.5 |
| Chest Press Strength | 689.1 Newtons STANDARD_DEVIATION 302.9 |
| Energy Level, Assessed Using the Hypogonadism Energy Diary (HED) | 29.0 Score STANDARD_DEVIATION 7.6 |
| Erectile Function Assessed by the International Index of Erectile Function (IIEF) Questionnaire | 6.7 Score STANDARD_DEVIATION 7.2 |
| Fat Body Mass Appendicular Fat Mass | 12.7 kg STANDARD_DEVIATION 3.7 |
| Fat Body Mass Trunk Fat Mass | 16.6 kg STANDARD_DEVIATION 5.3 |
| Fat Body Mass Whole Body Fat Mass | 30.9 kg STANDARD_DEVIATION 8.2 |
| Hematocrit | 44.8 percentage of total blood STANDARD_DEVIATION 3 |
| Hemoglobin | 14.8 g/dL STANDARD_DEVIATION 1.1 |
| Lean Body Mass Appendicular Lean Mass | 24.7 kg STANDARD_DEVIATION 3.5 |
| Lean Body Mass Trunk Lean Mass | 27.2 kg STANDARD_DEVIATION 3.4 |
| Lean Body Mass Whole Body Lean Mass | 55.4 kg STANDARD_DEVIATION 7 |
| Leg Press Strength | 2366.9 Newtons STANDARD_DEVIATION 576.3 |
| Lower Urinary Tract Symptoms, Ascertained Using the International Prostate Symptom Score (IPSS) | 6.9 Score STANDARD_DEVIATION 4.5 |
| Mood, Assessed by the Positive and Negative Affect Schedule (PANAS) Negative Affect (NA) Score | 14.7 Score STANDARD_DEVIATION 5 |
| Mood, Assessed by the Positive and Negative Affect Schedule (PANAS) Positive Affect (PA) Score | 34.9 Score STANDARD_DEVIATION 6.9 |
| Performance-based Physical Function, Assessed by Measuring Loaded Stair Climbing Power | 404.0 Watts STANDARD_DEVIATION 158.4 |
| Prostate Cancer-related Quality of Life, Measured Using the Hormonal and Sexual Domains of the Expan Hormonal Score | 87.1 Score STANDARD_DEVIATION 11.2 |
| Prostate Cancer-related Quality of Life, Measured Using the Hormonal and Sexual Domains of the Expan Sexual Function Score | 25.5 Score STANDARD_DEVIATION 18 |
| PSA <0.1 ng/mL | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 16 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants |
| Race/Ethnicity, Customized Non Hispanic or Latino | 63 Participants |
| Race/Ethnicity, Customized Not Known | 10 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized White | 117 Participants |
| Self-reported Physical Function, Assessed Using the Physical Function Component of MOS SF-36 (PF10) | 86.4 Score STANDARD_DEVIATION 18.2 |
| Sex/Gender, Customized Male | 136 Participants |
| Sexual Activity (PDQ-Question 4 Mean Score 0-12) | 1.6 Score STANDARD_DEVIATION 1.3 |
| Sexual Desire, Assessed by the DeRogatis Inventory of Sexual Function Sexual Desire (DISF-SD) | 15.6 Score STANDARD_DEVIATION 7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 64 |
| other Total, other adverse events | 49 / 66 | 47 / 64 |
| serious Total, serious adverse events | 3 / 66 | 1 / 64 |
Outcome results
None listed