Improved survival of men with prostate cancer has focused attention on the impact of treatment on quality of life, especially on sexual symptoms, physical dysfunction, and fatigue, which are important contributors to poor quality of life. Androgen deficiency is common and an important remediable contributor to these symptoms; however, uncertainty about the risk of testosterone replacement in men with a history of prostate cancer has rendered physicians reticent to use testosterone even in men who are deemed cured after a radical prostatectomy. A novel selective androgen receptor modulator - LY SARM - is ideal for alleviating symptoms of androgen deficiency and mitigating concerns about disease recurrence associated with testosterone therapy because it acts as an androgen agonist on the muscle, bone, and sexual function, but as an antagonist on the prostate. Our objective is to conduct a staged, double-blind, placebo-controlled, dose response study to determine the efficacy and safety of LY SARM in improving sexual symptoms, fatigue, and physical dysfunction in men with prostate cancer who have undergone radical prostatectomy for organ-localized prostate cancer, are deemed to be at low risk of recurrence, and who have androgen deficiency. In stage 1, 10 subjects will be randomized to either placebo or 1 mg dose. If no safety signal is observed, additional subjects will be randomized to 0, 1 or 5 mg dose.
Our first aim i s to compare 0, 1 or 5 mg of LY SARM in men, who have undergone radical prostatectomy for organ-localized prostate cancer, have symptomatic androgen deficiency, and with regard to sexual function (sexual activity score, sexual desire, erectile function, distress ad sexual life quality).
The second aim i s to compare the effects of 0, 1 or 5 mg of SARM on fatigue, well-being and affectivity balance, and disease-specific quality of life.
Our third aim i sto determine whether SARM administration improves muscle mass and strength, physical function, and aerobic capacity more than placebo. Men >19-years, who have undergone radical prostatectomy for organ-localized cancer (pT2,N0,M0), Gleason score <6, undetectable PSA (<0.1 ng/mL) for >2 years after radical prostatectomy and symptoms of sexual dysfunction, fatigue, or physical dysfunction, and low total (<300 ng/dL) and/or free testosterone <60 pg/ml, will be randomized to 0, 1 or 5 mg LY SARM daily for 3 months. Outcomes include changes in sexual symptoms (sexual activity score, sexual desire, erectile function, sexual distress, sexual life quality), affectivity balance, mood, fatigue, disease-specific quality of life, measures of physical function, muscle strength, and aerobic capacity (VO2max , VO2 peak, lactate threshold). We will monitor hematocrit, PSA, and biochemical recurrence, defined as PSA of >0.2 ng/mL with a confirmatory level of >0.2 ng/mL. Careful selection of subjects with very low risk of recurrence, rigorous safety monitoring, clear stopping rules, an independent DSMB, selection of symptomatic men with low testosterone, and good trial design (block randomization, placebo-controlled, blinded) will maximize the chances of successful outcome of this SARM trial in a very needy patient population.
Improved survival of men with prostate cancer has focused attention on the impact of treatment on quality of life, especially on symptoms of sexual dysfunction, physical dysfunction, and fatigue/ low vitality, which are important contributors to poor quality of life. Androgen deficiency is an important remediable contributor to these symptoms; in this regard, the discovery of a novel selective androgen receptor modulator (LY SARM), which acts as an antagonist on the prostate, but is an agonist on the muscle, bone, and sexual function, is a remarkable development because if effective, this SARM would be ideal for alleviating symptoms of androgen deficiency and mitigating concerns about disease recurrence associated with testosterone therapy. We propose to conduct a double-blind, placebo-controlled, parallel group, randomized trial to determine the efficacy and safety of a SARM in improving sexual symptoms, fatigue/low vitality, and physical dysfunction and health-related quality of life in men with prostate cancer who have undergone radical prostatectomy for organ- localized cancer, have low risk of disease recurrence, and have androgen deficiency.
