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Improving Quality of Life of Prostate Cancer Survivors With Androgen Deficiency

Phase 2
Active, not recruiting
Conditions
Prostate Cancer
Interventions
Registration Number
NCT03716739
Lead Sponsor
Dana-Farber Cancer Institute
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
137
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Treatment ArmTestosterone Cypionate 100 MG/MLWeekly IM administration of 100 mg testosterone cypionate for 12 weeks.
Control ArmPlaceboWeekly IM administration of placebo for 12 weeks.
Primary Outcome Measures
NameTimeMethod
PSA Recurrence5-8 months

The proportion of enrolled participations with PSA recurrence.

Change in sexual activity5-8 months

Change in sexual activity is assessed by the Psychosexual Daily Questionnaire (PDQ), question 4. Subjects complete the 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 desire, sexual enjoyment, and mood are rated on a 7-point Likert-type scale from 0 to 7, with 0 indicating none and 7 indicating high. Activity is assessed using a checklist. Subjects record whether they had sexual daydreams; anticipation of sex; flirting; sexual interactions; and erection, masturbation, intercourse, orgasm, and ejaculation on each of the 7 days. The value is recorded as 0 (none) or 1 (any) for analysis. Weekly value is the sum of "any" responses for the week. The sexual activity score is the average of the weekly values. The score is 0 if no activity has taken place. Higher values indicate more activity and lower values indicate lower activity.

Secondary Outcome Measures
NameTimeMethod
Change in PSABaseline to 5-8 months

Change in PSA from baseline to final assessment

Clinical Disease Recurrence5-8 months

Proportion of enrolled participants with clinical disease recurrence

Change in sexual desire5-8 months

Sexual desire will be assessed by DeRogatis Inventory of Sexual Function. HRQOL 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 HRQOL

Change in erectile function5-8 months

Erectile function will be assessed by IIEF. The International Index of Erectile Function (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 level5-8 months

Energy level will be 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 score indicate lower energy (or more tiredness0 and higher scores indicate more energy (less tiredness).

Change in mood5-8 months

Mood and well-being will be assessed by PANAS.

Change in physical function5-8 months

Physical function will be assessed by measuring stair climbing power with and without a standardized load, walking speed.

Change in self-reported physical function5-8 months

Self-reported physical function will be assessed using physical function domain of MOS SF-36 (PF10)

Change in maximal voluntary strength5-8 months

Maximal voluntary strength in the leg press exercise by the 1-RM method.

Change in lean body mass5-8 months

Lean body mass using dual energy X-ray absorptiometry (DXA).

Change in hormone Levels5-8 months

Total testosterone, DHT and estradiol will be measured using LC-MS/MS in a CDC-certified laboratory, free testosterone by equilibrium dialysis.

Change in aerobic capacity5-8 months

Aerobic capacity will be assessed by measuring VO2 peak.

Trial Locations

Locations (3)

Johns Hopkins University

🇺🇸

Baltimore, Maryland, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

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