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: Recruiting
• 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 (Estimated): 142
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shalender Bhasin, MD; Phone Number: 617-525-9150; Email: sbhasin@partners.org
• Study Contact Backup: Name: Fabiola Privat; Phone Number: 617-525-9132; Email: fprivat@bwh.harvard.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University
      • Contact: Julia Faranetta; Phone Number: 410-502-2776; Email: jfarane1@jhmi.edu
      • Principal Investigator: Arthur Burnett, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Shalender Bhasin, MD; Phone Number: 617-525-9040; Email: sbhasin@partners.org
      • Principal Investigator: Shalender Bhasin, MD
      • Contact: Nancy Latham, PhD; Email: nklatham@bwh.harvard.edu
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana Farber Cancer Institute
      • Principal Investigator: Shalender Bhasin, MD
      • Contact: Shalender Bhasin
      • Contact: Nancy Latham, PhD; Email: nklatham@bwh.harvard.edu

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
Change in sexual activity	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.	5-8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in erectile function	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.	5-8 months
Change in sexual desire	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	5-8 months
Change in energy level	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).	5-8 months
Change in mood	Mood and well-being will be assessed by PANAS.	5-8 months
Change in physical function	Physical function will be assessed by measuring stair climbing power with and without a standardized load, walking speed.	5-8 months
Change in self-reported physical function	Self-reported physical function will be assessed using physical function domain of MOS SF-36 (PF10)	5-8 months
Change in maximal voluntary strength	Maximal voluntary strength in the leg press exercise by the 1-RM method.	5-8 months
Change in lean body mass	Lean body mass using dual energy X-ray absorptiometry (DXA).	5-8 months
Change in hormone Levels	Total testosterone, DHT and estradiol will be measured using LC-MS/MS in a CDC-certified laboratory, free testosterone by equilibrium dialysis.	5-8 months
Change in aerobic capacity	Aerobic capacity will be assessed by measuring VO2 peak.	5-8 months

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

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2019
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): October 1, 2024

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 (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: 18-733; 1R01AG060539-01 (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