A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer

This research study is studying the use of a targeted therapy called LY SARM, which is an investigational drug from a new class of molecules called Selective Androgen Receptor Modulators (SARMs) as a possible improvement in quality of life for participants who have undergone radical prostatectomy. Androgens are a group of hormones that play a role in male traits and reproductive activity.

The names of the study interventions involved in this study are:

- LY2452473

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Placebo; Drug: LY2452473

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved LY SARM/LY2452473 as a treatment for any disease.

In this research study, the investigators are studying a new investigational drug called LY SARM (LY2452473). Concerns about the potential adverse effects of testosterone on the prostate have led to the development of molecules called SARMs (Selective Androgen Receptor Modulators). This investigational drug may improve sexual function, quality of life, muscle and bone mass in men with prostate cancer. This molecule was chosen because there is some evidence that shows it may help to improve sexual function and aid in the improvement of muscle mass while not having any influence on the prostate.

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • John Hopkins Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center (Referring site only)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria

• Age 19 years of age or older

• History of prostate cancer

  • Stage pathological tumor-2 (pT2) N0, M0 lesions (If American Joint Committee on Cancer (AJCC) staging is not available in medical records, the investigators will infer the staging based on extensive review of the pathology report)
  • Combined Gleason score < 7 (3+4)
  • Radical prostatectomy two or more years ago
  • Preoperative prostate-specific antigen (PSA)<10 ng/ml (if pre-operative PSA is not available in medical records, low-risk subjects with a Gleason score of 6(3+3) and who are at least 5 years out of surgery will be considered for enrollment)
  • PSA <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

• Serum testosterone, measured by Liquid chromatography-tandem mass spectrometry (LC-MS/MS), <300 mg/dL and/or free testosterone by equilibrium dialysis <60 pg/mL.

  * Derogatis Index of Sexual Function Male II (DISF-M-II) score ≤20, fatigue (FACIT-F score <30), or physical dysfunction (self-reported difficulty in walking a 1/4 mile or climbing two flights of stairs, short physical performance battery score 4 to 9).

• Ability to understand and the willingness to sign a written informed consent document.

  • Agree to use adequate contraception prior to receiving the study drug, for the duration of study participation, and 4 months after completion of LY SARM administration.

Exclusion Criteria

• History of radiation monotherapy
• History of androgen deprivation therapy
• Use of testosterone, dehydroepiandrosterone (DHEA), estrogens, gonadotropin-releasing hormone (GnRH) analogs, antiandrogens, spironolactone, ketoconazole, recombinant human growth hormone (rhGH), or megestrol acetate within the past 6 months
• Use of prednisone 20 mg daily or equivalent doses of other glucocorticoids for more than two weeks within the past 6 months
• Use of Clarithromycin, telithromycin, chloramphenicol, itraconazole, nefazodone, cobicistat within the past 6 months
• Use of penile implants, vacuum pump devices, intra-cavernosal injections
• Hematocrit >50%
• Serum creatinine >2.5 mg/dL
• Aspartate aminotransferase (AST) greater than 3x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) greater than 3x ULN
• Hemoglobin A1c >7.5%
• Body mass index (BMI) >40 kg/m2
• Diabetes requiring insulin therapy
• Severe untreated sleep apnea (treatment is defined as therapy with continuous positive airway pressure (CPAP), BiPAP, adaptive servo-ventilation (ASV), or other positive air pressure device)
• Uncontrolled heart failure (NYHA class 3 or 4)
• History of HIV
• Myocardial infarction within the last 3 months
• Acute coronary syndrome within the last 3 months
• Revascularization surgery within the last 3 months
• Stroke within the last 3 months
• Diagnosed schizophrenia or bipolar disorder or untreated depression
• Not appropriate for study based on physician discretion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Subjects who meet the eligibility criteria, will be randomized, to either placebo, LY SARM Dose 1, LY SARM Dose 2 or LY SARM Dose 3 daily, oral per cycle.	Drug: Placebo; The participants will receive pills containing no active drug.; Other Names: Inactive comparator
ACTIVE_COMPARATOR: LY2452473 Dose 1; Subjects who meet the eligibility criteria, will be randomized, to either placebo, LY SARM Dose 1, LY SARM Dose 2 or LY SARM Dose 3 daily, oral per cycle.	Drug: LY2452473; LY2452473 is a selective androgen receptor modulator which is agonist on the muscle but which spares the prostate.; Other Names: Selective Androgen Receptor Modulator
ACTIVE_COMPARATOR: LY2452473 Dose 2; Subjects who meet the eligibility criteria, will be randomized, to either placebo, LY SARM Dose 1 or LY SARM Dose 2 or LY SARM Dose 3 daily, oral per cycle.	Drug: LY2452473; LY2452473 is a selective androgen receptor modulator which is agonist on the muscle but which spares the prostate.; Other Names: Selective Androgen Receptor Modulator
ACTIVE_COMPARATOR: LY2452473 Dose 3; Subjects who meet the eligibility criteria, will be randomized, to either placebo, LY SARM Dose 1, LY SARM Dose 2 or LY SARM Dose 3 daily, oral per cycle.	Drug: LY2452473; LY2452473 is a selective androgen receptor modulator which is agonist on the muscle but which spares the prostate.; Other Names: Selective Androgen Receptor Modulator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Sexual Activity Score of Psychosexual Daily Questionnaire (PDQ-4)	The primary outcome is change in sexual activity score, assessed by the Psychosexual Daily Questionnaire (PDQ). The questionnaire covered 3 different domains: 1) sexual desire, enjoyment, and performance; 2) sexual activity score; and 3) mood. Sexual activity was assessed using a checklist format (12-item) and the score range of 0 to 12 with higher scores representing better sexual activity.	12 weeks from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in All Domains of International Index of Erectile Function (IIEF)	IIEF is a validated, 15-item questionnaire that assesses 5 domains of sexual function: erectile function (range 1-30), orgasmic function (range 0-10), sexual desire (range 2-10), intercourse satisfaction (range 0-15), and overall sexual satisfaction (range 2-10). Each question was answered on a 6-point or 5-point scale from 0/1 to 5 (best) with a total possible score (sum of 5 domains) range of 5 to 75 with higher scores representing better function.	12 weeks from baseline
Change in Sexual Activity, Interest, and Desire Scale (SAID)	The Sexual Activity, Interest, and Desire Scale (SAID) is an 8-item questionnaire that evaluates 3 response domains, including sexual thinking, sexual arousal, and sexual activity. The score was linearly transformed to a 0 to 100 scale for each item. The average score ranges 0-100. The higher the score, the better the sexual function.	12 weeks from baseline
Change in Derogatis Index of Sexual Function Male II (DISF-M-II)	Derogatis Index of Sexual Function Male II (DISF-M-II) is a 25-item questionnaire that provides an estimate of perceived quality of sexual activities in 5 response domains: sexual desire/drive (range 0-33), sexual arousal (range 0-33), sexual activity (range 0-35), orgasm (range 0-26), and sexual satisfaction/partner relationship (range 0-25). The total possible score (sum of 5 domains) range of 0 to 152 with higher scores representing better function.	12 weeks from baseline
Change in Three Domains of Men's Sexual Health Questionnaire (MSHQ)	Men's Sexual Health Questionnaire (MSHQ), a 25-item questionnaire, assesses sexual function and satisfaction. It consists 5 domains: Erection (3 items, ranging from 0 to 15 (best)), Ejaculation (7 items, ranging from 1 to 35 (best)), Satisfaction (6 items, ranging from 6 to 30 (best)), Sexual desire (4 items, ranging 4-20 (best)), and Sexual activity (3 items, ranging 3-15 (best)). Erection, Ejaculation and Satisfaction domains were measured and the higher score representing better sexual function and satisfaction.	12 weeks from baseline
Change in Two Domains of Expanded Prostate Cancer Index Composite (EPIC)	Expanded Prostate Cancer Index Composite (EPIC) is a 50-item, comprehensive instrument designed to evaluate patient function and bother after prostate cancer treatment. Of its four domains, the sexual domain (range 0-100) and hormonal domain (range 0-100) were utilized. The response for each item is standardized to a 0 to 100 scale. Higher score yields better quality of life.	12 weeks from baseline
Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale	The FACIT Fatigue Scale is a 13-item questionnaire that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four-point scale (4 = not at all fatigued to 0 = very much fatigued). Score ranges 0-52. The higher the score, the better the quality of life.	12 weeks from baseline
Change in Hypogonadism Energy Diary (HED)	Hypogonadism Energy Diary (HED) is a 4-item questionnaire that intended to assess real-time energy levels. Score ranges 0 to100 with higher scores representing higher energy. each question uses an 11-point numerical rating scale (0-10) with 10 corresponding to full of energy or extreme tiredness. HED score was the average of the scores for these 4 items. Scores were linearly transformed to a 0 to 100 scale. Higher scores representing higher energy.	12 weeks from baseline
Change in International Prostate Symptom Score (IPSS)	International Prostate Symptom Score (IPSS) is a 8-item, extensively validated and widely used self-reported measure of lower urinary tract symptoms questionnaire. It includes Urinary Symptoms (item1-7, range 0-35) and Quality of Life Due to Urinary Symptoms (item 8, range 0-6). The higher the score, the severer of the urinary symptoms and worse quality of life due to symptoms.	12 weeks from baseline
Change in Positive and Negative Affect Scale (PANAS)	The Positive and Negative Affect Schedule (PANAS) is a self-report questionnaire that consists of two 10-item scales to measure both positive and negative affect. Each item is rated on a 5-point scale of 1 (very slightly or not at all) to 5 (extremely). Score ranges 10-50 for both positive and negative affect. The higher scores represent higher levels of positive/negative affect.	12 weeks from baseline
Change in Body Mass Using DXA	Whole body, appendicular, and trunk lean mass were measured using dual energy X- ray absorptiometry (DXA), calibrated using a soft tissue phantom before each scan.	12 weeks from baseline
Change of Maximal Voluntary Muscle Strength	The maximal voluntary muscle strength was measured in the leg press exercise using the 1-repetition method	12 weeks from baseline
Change in Gait Speed in 6-minute Walk	Tests of Physical Function and Task-Specific Performance measured by gait speed in 6-min walk	12 weeks from baseline
Change of 50 Meters Walk Tests- Unloaded /Loaded	Tests of Physical Function and Task-Specific Performance measured by 50-meter timed walk + 20% load carry. Physical Function was evaluated using test of 50-meter loaded walking speed. One test consisted of walking 50 meters as rapidly as possible without running (unloaded) while the second test required participants to carry a load equivalent to 20% of their baseline body weight evenly distributed in two canvas tote bags(loaded). Time was measured electronically with a digital clock. Speed in meters per second is calculated by the following: 50/time.	12 weeks from baseline
Change in Power of Stair Climbing Tests- Unloaded/Loaded	Tests of Physical Function and Task-Specific Performance measured by Stair-climbing power +/- 20% load carry. Physical Function was evaluated using two tests of stair climb power using an indoor 12-step staircase. One test consisted of ascending the 12-steps as rapidly as possible without running (unloaded stair climb) while the second test required participants to carry a load equivalent to 20% of their baseline body weight evenly distributed in two canvas tote bags (loaded stair climb). Time to ascend the stairs was measured electronically with a digital clock and switch mats placed at the base of the steps and on the 12th step. Power in watts is calculated by the following: [body weight (kilograms) * distance (meters)/ (time/60)] /6.12.	12 weeks from baseline
Change in Serum Total Testosterone Level	Serum total testosterone levels during screening was measured in the Quest Diagnostics Laboratory, Chantilly, VA, using liquid chromatography tandem mass spectrometry (LC-MS/MS) method certified by the Hormone Standardization Program for Testosterone (HoST) of the Centers for Disease Control and Prevention, Atlanta, Georgia.	12 weeks from baseline
Change in Free Testosterone Level	Free testosterone level for screening was measured using an equilibrium dialysis method.	12 weeks from baseline
Change in Serum Sex Hormone-binding Globulin (SHBG) Level	Serum SHBG level was measured using two-site directed immuno-chemiluminescence assays with sensitivity 2.5 nmol/L, and coefficients of variation less than 10% in low, medium and high range	12 weeks from baseline
Change in Serum Luteinizing Hormone (LH) Level	Serum LH level was measured using two-site directed immuno-chemiluminescence assays with sensitivity 0.1 U/L, and coefficients of variation less than 10% in low, medium and high range	12 weeks from baseline
Change in Estradiol Levels	Estradiol level was measured by LC-MS/MS.	12 weeks from baseline
Change of White Blood Cell	White Blood Cell was measured for safety monitoring.	12 weeks from baseline
Change of Red Blood Cell	Red Blood Cell was measured for safety monitoring.	12 weeks from baseline
Change in Hematocrit	Hematocrit was measured for safety monitoring.	12 weeks from baseline
Change in Hemoglobin	Hemoglobin was measured for safety monitoring.	12 weeks from baseline
Change of Mean Corpuscular Volume (MCV)	Mean corpuscular volume was measured for safety monitoring.	12 weeks from baseline
Change of Red Blood Cell Distribution Width (RDW)	Red blood cell distribution width (RDW) was measured for safety monitoring. RDW was calculated with: standard deviation of the mean cell size divided by the mean corpuscular volume of the red cells multiplied by 100	12 weeks from baseline
Change in Platelet Count	Platelet count was measured for safety monitoring.	12 weeks from baseline
Change of Aspartate Aminotransferase (AST)	Aspartate aminotransferase was measured for safety monitoring.	12 weeks from baseline
Change of Alanine Aminotransferase (ALT)	Alanine aminotransferase was measured for safety monitoring.	12 weeks from baseline
Change of Total Bilirubin	Total Bilirubin was measured for safety monitoring.	12 weeks from baseline
Change in Serum Alkaline Phosphatase	Serum alkaline phosphatase was measured for safety monitoring.	12 weeks from baseline
Change of Lipid Panel	Plasma lipids were measured for safety monitoring.	12 weeks from baseline
Change in Fasting Glucose Levels	Glucose will be measured in a fasting serum sample at Quest Lab.	12 weeks from baseline
Change in Insulin	Insulin will be measured using an immunoassay at Quest lab.	12 weeks from baseline

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: National Institute of Nursing Research (NINR)

Publications and helpful links

General Publications

• Pencina KM, Burnett AL, Storer TW, Guo W, Li Z, Kibel AS, Huang G, Blouin M, Berry DL, Basaria S, Bhasin S. A Selective Androgen Receptor Modulator (OPK-88004) in Prostate Cancer Survivors: A Randomized Trial. J Clin Endocrinol Metab. 2021 Jul 13;106(8):2171-2186. doi: 10.1210/clinem/dgab361.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 29, 2016
• Primary Completion (ACTUAL): October 31, 2020
• Study Completion (ACTUAL): October 31, 2020

Study Registration Dates

• First Submitted: July 6, 2015
• First Submitted That Met QC Criteria: July 15, 2015
• First Posted (ESTIMATE): July 16, 2015

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Prostate Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens
• Other Study ID Numbers: 15-120