Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Collaborator:
National Institute of Nursing Research (NINR)
Information provided by (Responsible Party):
Shalender Bhasin, MD, Dana-Farber Cancer Institute

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


Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: LY2452473 Drug: Placebo Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 114 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Official Title: A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer
Actual Study Start Date : February 29, 2016
Actual Primary Completion Date : October 31, 2020
Actual Study Completion Date : October 31, 2020


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 Name: 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 Name: 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 Name: 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 Name: Selective Androgen Receptor Modulator




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Change in Free Testosterone Level [ Time Frame: 12 weeks from baseline ]
    Free testosterone level for screening was measured using an equilibrium dialysis method.

  17. 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

  18. 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

  19. Change in Estradiol Levels [ Time Frame: 12 weeks from baseline ]
    Estradiol level was measured by LC-MS/MS.

  20. Change of White Blood Cell [ Time Frame: 12 weeks from baseline ]
    White Blood Cell was measured for safety monitoring.

  21. Change of Red Blood Cell [ Time Frame: 12 weeks from baseline ]
    Red Blood Cell was measured for safety monitoring.

  22. Change in Hematocrit [ Time Frame: 12 weeks from baseline ]
    Hematocrit was measured for safety monitoring.

  23. Change in Hemoglobin [ Time Frame: 12 weeks from baseline ]
    Hemoglobin was measured for safety monitoring.

  24. Change of Mean Corpuscular Volume (MCV) [ Time Frame: 12 weeks from baseline ]
    Mean corpuscular volume was measured for safety monitoring.

  25. 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

  26. Change in Platelet Count [ Time Frame: 12 weeks from baseline ]
    Platelet count was measured for safety monitoring.

  27. Change of Aspartate Aminotransferase (AST) [ Time Frame: 12 weeks from baseline ]
    Aspartate aminotransferase was measured for safety monitoring.

  28. Change of Alanine Aminotransferase (ALT) [ Time Frame: 12 weeks from baseline ]
    Alanine aminotransferase was measured for safety monitoring.

  29. Change of Total Bilirubin [ Time Frame: 12 weeks from baseline ]
    Total Bilirubin was measured for safety monitoring.

  30. Change in Serum Alkaline Phosphatase [ Time Frame: 12 weeks from baseline ]
    Serum alkaline phosphatase was measured for safety monitoring.

  31. Change of Lipid Panel [ Time Frame: 12 weeks from baseline ]
    Plasma lipids were measured for safety monitoring.

  32. Change in Fasting Glucose Levels [ Time Frame: 12 weeks from baseline ]
    Glucose will be measured in a fasting serum sample at Quest Lab.

  33. Change in Insulin [ Time Frame: 12 weeks from baseline ]
    Insulin will be measured using an immunoassay at Quest lab.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02499497


Locations
Layout table for location information
United States, Florida
University of Florida
Gainesville, Florida, United States, 32611
United States, Maryland
John Hopkins Medical Center
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Beth Israel Deaconess Medical Center (Referring site only)
Boston, Massachusetts, United States, 02115
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Institute of Nursing Research (NINR)
Investigators
Layout table for investigator information
Principal Investigator: Shalender Bhasin, MD Brigham and Women's Hospital
  Study Documents (Full-Text)

Documents provided by Shalender Bhasin, MD, Dana-Farber Cancer Institute:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Shalender Bhasin, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02499497    
Other Study ID Numbers: 15-120
First Posted: July 16, 2015    Key Record Dates
Results First Posted: September 28, 2021
Last Update Posted: September 28, 2021
Last Verified: September 2021
Keywords provided by Shalender Bhasin, MD, Dana-Farber Cancer Institute:
Prostate Cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs