A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer

Dana-Farber Cancer Institute

Status and phase: Completed; Phase 2

Conditions: Prostate Cancer

Treatments: Drug: Placebo; Drug: LY2452473

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02499497

15-120

Details and patient eligibility

About

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

Full 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.

Enrollment: 114 patients

Sex: Male

Ages: 19+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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114 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

LY2452473 Dose 1

Active Comparator group

Description:

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.

Treatment:

Drug: LY2452473

LY2452473 Dose 2

Active Comparator group

Description:

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.

Treatment:

Drug: LY2452473

LY2452473 Dose 3

Active Comparator group

Description:

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.

Treatment:

Drug: LY2452473