Clinical trial NCT02499497: A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer
Official title: A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Prostate Cancer
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Institute of Nursing Research (NINR)
First posted: 2015-07-16
Enrollment: 114
Sex: MALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Change in Sexual Activity Score of Psychosexual Daily Questionnaire (PDQ-4)
timeFrame: 12 weeks from baseline
Secondary outcomes:
measure: Change in All Domains of International Index of Erectile Function (IIEF)
timeFrame: 12 weeks from baseline
measure: Change in Sexual Activity, Interest, and Desire Scale (SAID)
timeFrame: 12 weeks from baseline
measure: Change in Derogatis Index of Sexual Function Male II (DISF-M-II)
timeFrame: 12 weeks from baseline
measure: Change in Three Domains of Men's Sexual Health Questionnaire (MSHQ)
timeFrame: 12 weeks from baseline
measure: Change in Two Domains of Expanded Prostate Cancer Index Composite (EPIC)
timeFrame: 12 weeks from baseline
measure: Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale
timeFrame: 12 weeks from baseline
measure: Change in Hypogonadism Energy Diary (HED)
timeFrame: 12 weeks from baseline
measure: Change in International Prostate Symptom Score (IPSS)
timeFrame: 12 weeks from baseline
measure: Change in Positive and Negative Affect Scale (PANAS)
timeFrame: 12 weeks from baseline
measure: Change in Body Mass Using DXA
timeFrame: 12 weeks from baseline
measure: Change of Maximal Voluntary Muscle Strength
timeFrame: 12 weeks from baseline
measure: Change in Gait Speed in 6-minute Walk
timeFrame: 12 weeks from baseline
measure: Change of 50 Meters Walk Tests- Unloaded /Loaded
timeFrame: 12 weeks from baseline
measure: Change in Power of Stair Climbing Tests- Unloaded/Loaded
timeFrame: 12 weeks from baseline
measure: Change in Serum Total Testosterone Level
timeFrame: 12 weeks from baseline
measure: Change in Free Testosterone Level
timeFrame: 12 weeks from baseline
measure: Change in Serum Sex Hormone-binding Globulin (SHBG) Level
timeFrame: 12 weeks from baseline
measure: Change in Serum Luteinizing Hormone (LH) Level
timeFrame: 12 weeks from baseline
measure: Change in Estradiol Levels
timeFrame: 12 weeks from baseline
measure: Change of White Blood Cell
timeFrame: 12 weeks from baseline
measure: Change of Red Blood Cell
timeFrame: 12 weeks from baseline
measure: Change in Hematocrit
timeFrame: 12 weeks from baseline
measure: Change in Hemoglobin
timeFrame: 12 weeks from baseline
measure: Change of Mean Corpuscular Volume (MCV)
timeFrame: 12 weeks from baseline
measure: Change of Red Blood Cell Distribution Width (RDW)
timeFrame: 12 weeks from baseline
measure: Change in Platelet Count
timeFrame: 12 weeks from baseline
measure: Change of Aspartate Aminotransferase (AST)
timeFrame: 12 weeks from baseline
measure: Change of Alanine Aminotransferase (ALT)
timeFrame: 12 weeks from baseline
measure: Change of Total Bilirubin
timeFrame: 12 weeks from baseline
measure: Change in Serum Alkaline Phosphatase
timeFrame: 12 weeks from baseline
measure: Change of Lipid Panel
timeFrame: 12 weeks from baseline
measure: Change in Fasting Glucose Levels
timeFrame: 12 weeks from baseline
measure: Change in Insulin
timeFrame: 12 weeks from baseline
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Baltimore
country: United States
facility: John Hopkins Medical Center
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (Referring site only)
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shalender Bhasin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.