A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer

• ClinicalTrials.gov Identifier: NCT02499497
• Recruitment Status: Completed
• First Posted: July 16, 2015
• Results First Posted: September 28, 2021
• Last Update Posted: September 28, 2021
• Sponsor: Dana-Farber Cancer Institute
• Collaborator: National Institute of Nursing Research (NINR)
• Information provided by (Responsible Party): Shalender Bhasin, MD, Dana-Farber Cancer Institute

Tracking Information

• First Submitted Date: July 6, 2015
• First Posted Date: July 16, 2015
• Results First Submitted Date: August 23, 2021
• Results First Posted Date: September 28, 2021
• Last Update Posted Date: September 28, 2021
• Actual Study Start Date: February 29, 2016
• Actual Primary Completion Date: October 31, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 27, 2021)

Change in Sexual Activity Score of Psychosexual Daily Questionnaire (PDQ-4) [ Time Frame: 12 weeks from baseline ]

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.

• Original Primary Outcome Measures (submitted: July 15, 2015): Harbor-UCLA 7-day Sexual Function Questionnaire [ Time Frame: 6 Months ]

Current Secondary Outcome Measures (submitted: September 27, 2021)

• Change in All Domains of International Index of Erectile Function (IIEF) [ Time Frame: 12 weeks from baseline ]
  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.
• Change in Sexual Activity, Interest, and Desire Scale (SAID) [ Time Frame: 12 weeks from baseline ]
  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.
• Change in Derogatis Index of Sexual Function Male II (DISF-M-II) [ Time Frame: 12 weeks from baseline ]
  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.
• Change in Three Domains of Men's Sexual Health Questionnaire (MSHQ) [ Time Frame: 12 weeks from baseline ]
  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.
• Change in Two Domains of Expanded Prostate Cancer Index Composite (EPIC) [ Time Frame: 12 weeks from baseline ]
  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.
• Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale [ Time Frame: 12 weeks from baseline ]
  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.
• Change in Hypogonadism Energy Diary (HED) [ Time Frame: 12 weeks from baseline ]
  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.
• Change in International Prostate Symptom Score (IPSS) [ Time Frame: 12 weeks from baseline ]
  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.
• Change in Positive and Negative Affect Scale (PANAS) [ Time Frame: 12 weeks from baseline ]
  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.
• Change in Body Mass Using DXA [ Time Frame: 12 weeks from baseline ]
  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.
• Change of Maximal Voluntary Muscle Strength [ Time Frame: 12 weeks from baseline ]
  The maximal voluntary muscle strength was measured in the leg press exercise using the 1-repetition method
• Change in Gait Speed in 6-minute Walk [ Time Frame: 12 weeks from baseline ]
  Tests of Physical Function and Task-Specific Performance measured by gait speed in 6-min walk
• Change of 50 Meters Walk Tests- Unloaded /Loaded [ Time Frame: 12 weeks from baseline ]
  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.
• Change in Power of Stair Climbing Tests- Unloaded/Loaded [ Time Frame: 12 weeks from baseline ]
  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.
• Change in Serum Total Testosterone Level [ Time Frame: 12 weeks from baseline ]
  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.
• Change in Free Testosterone Level [ Time Frame: 12 weeks from baseline ]
  Free testosterone level for screening was measured using an equilibrium dialysis method.
• Change in Serum Sex Hormone-binding Globulin (SHBG) Level [ Time Frame: 12 weeks from baseline ]
  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
• Change in Serum Luteinizing Hormone (LH) Level [ Time Frame: 12 weeks from baseline ]
  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
• Change in Estradiol Levels [ Time Frame: 12 weeks from baseline ]
  Estradiol level was measured by LC-MS/MS.
• Change of White Blood Cell [ Time Frame: 12 weeks from baseline ]
  White Blood Cell was measured for safety monitoring.
• Change of Red Blood Cell [ Time Frame: 12 weeks from baseline ]
  Red Blood Cell was measured for safety monitoring.
• Change in Hematocrit [ Time Frame: 12 weeks from baseline ]
  Hematocrit was measured for safety monitoring.
• Change in Hemoglobin [ Time Frame: 12 weeks from baseline ]
  Hemoglobin was measured for safety monitoring.
• Change of Mean Corpuscular Volume (MCV) [ Time Frame: 12 weeks from baseline ]
  Mean corpuscular volume was measured for safety monitoring.
• Change of Red Blood Cell Distribution Width (RDW) [ Time Frame: 12 weeks from baseline ]
  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
• Change in Platelet Count [ Time Frame: 12 weeks from baseline ]
  Platelet count was measured for safety monitoring.
• Change of Aspartate Aminotransferase (AST) [ Time Frame: 12 weeks from baseline ]
  Aspartate aminotransferase was measured for safety monitoring.
• Change of Alanine Aminotransferase (ALT) [ Time Frame: 12 weeks from baseline ]
  Alanine aminotransferase was measured for safety monitoring.
• Change of Total Bilirubin [ Time Frame: 12 weeks from baseline ]
  Total Bilirubin was measured for safety monitoring.
• Change in Serum Alkaline Phosphatase [ Time Frame: 12 weeks from baseline ]
  Serum alkaline phosphatase was measured for safety monitoring.
• Change of Lipid Panel [ Time Frame: 12 weeks from baseline ]
  Plasma lipids were measured for safety monitoring.
• Change in Fasting Glucose Levels [ Time Frame: 12 weeks from baseline ]
  Glucose will be measured in a fasting serum sample at Quest Lab.
• Change in Insulin [ Time Frame: 12 weeks from baseline ]
  Insulin will be measured using an immunoassay at Quest lab.

Original Secondary Outcome Measures (submitted: July 15, 2015)

• disease-specific quality of life questionnaire [ Time Frame: 6 Months ]
  HRQOL
• Fatigue The Functional Assessment of Chronic Illness Therapy (FACIT -1) Fatigue Scale [ Time Frame: 6 Months ]
• Lean body mass using DXA [ Time Frame: 6 months ]
• Number of participants with Adverse Events [ Time Frame: 6 months ]
• muscle strength [ Time Frame: 6 months ]
  The one-repetition maximum (1RM) test
• Continuous Scale Physical Functional Performance 10 [ Time Frame: 6 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer
• Official Title: A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer

Brief Summary

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

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Supportive Care
• Condition: Prostate Cancer

Intervention

• Drug: LY2452473
  LY2452473 is a selective androgen receptor modulator which is agonist on the muscle but which spares the prostate.
  Other Name: Selective Androgen Receptor Modulator
• Drug: Placebo
  The participants will receive pills containing no active drug.
  Other Name: Inactive comparator

Study Arms

• 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.
  Intervention: Drug: Placebo
• 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.
  Intervention: Drug: LY2452473
• 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.
  Intervention: Drug: LY2452473
• 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.
  Intervention: Drug: LY2452473

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 3, 2019): 114
• Original Estimated Enrollment (submitted: July 15, 2015): 350
• Actual Study Completion Date: October 31, 2020
• Actual Primary Completion Date: October 31, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 19 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02499497
• Other Study ID Numbers: 15-120
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Shalender Bhasin, MD, Dana-Farber Cancer Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Dana-Farber Cancer Institute
• Original Study Sponsor: Same as current
• Collaborators: National Institute of Nursing Research (NINR)

Investigators

• Principal Investigator: Shalender Bhasin, MD; Brigham and Women's Hospital

• PRS Account: Dana-Farber Cancer Institute
• Verification Date: September 2021