Conditions: Prostate Cancer
Keywords: Prostate Cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 114
Healthy volunteers: no

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.

Arms:
arm 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. arm 2: 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. arm 3: 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. arm 4: 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.

Interventions: intervention 1: LY2452473 intervention 2: Placebo
Intervention descriptions: intervention 1: LY2452473 is a selective androgen receptor modulator which is agonist on the muscle but which spares the prostate. intervention 2: The participants will receive pills containing no active drug.

Protocol document:
Prot_SAP_000.pdf: 
DF/HCC BIOMEDICAL PROTOCOL 
Version:  February 5, 2019 
 
NCI Protocol #: 
Not Applicable 
 
DF/HCC Protocol #:  15-120 
DF/HCC Biomedical Protocol:  02/05/2019 
 
TITLE: A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer 
Protocol Version Date: 02/05/2019 Version  20.0 
 
 
Coordinating Center: 
 
 
Brigham and Women’s Hospital 
 
*Principal Investigator (PI): 
Shalender Bhasin, MD 
 
Brigham and Women’s Hospital 
 
 
Other Investigators: 
Shehzad Basaria, MD 
Brigham and Women’s Hospital 
 
 
Adam Kibel, MD 
Dana Farber Cancer Institute 
 
 
Donna Berry, PhD 
Dana Farber Cancer Institute 
 
 
Grace Huang, MD 
Brigham and Women’s Hospital 
 
 
Arthur Burnett, MD 
Johns Hopkins Medical Institute 
 
 
Thomas Storer, PhD 
Brigham and Women’s Hospital 
 
 
Peter Chang, MD, MPH 
Beth Israel Deaconess Medical Center 
 
Statistician: 
Study Coordinators: 
Maricelle Ramirez 
Brigham and Women’s Hospital 
617-525-9027 
FAX: 617-525-9148 
mramirez5@partners.org 
 
Responsible Research Nurse: 
Haley J. Schram, N.P. 
Brigham and Women’s Hospital 
617-525-9027 
FAX: 617-525-9196 
hschram@partners.org 
Karol Pencina, PhD 
Brigham and Women’s Hospital 
617-525-9049 
kpencina@partners.org 
 
Emily Heckel 
Brigham and Women’s Hospital 
617-525-8407  
FAX: 617-525-9148 
eheckel@partners.org 
Responsible Data Manager: N/A  
 
 
 
 
 
 
 
 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 02/05/2019 
2 
 
 
 
NCI-Supplied Agent(s):  N/A 
Other Agent(s):  N/A  
 
 
Below, please describe the IND Status of this study by choosing IND #/Sponsor OR Exemption from IND 
requirements, making sure to delete the inapplicable field(s). 
 
IND#: 126806.  We have now received final approval from the FDA on our IND. 
IND Sponsor: Shalender Bhasin, the PI of the study is the IND holder. 
 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 02/05/2019 
3 
 
TABLE OF CONTENTS 
1. 
OBJECTIVES ......................................................................................................................5 
1.1 
Study Design ....................................................................................................................... 5 
1.2 
Primary Objectives.............................................................................................................. 5 
1.3 
Secondary Objectives.......................................................................................................... 5 
2. 
BACKGROUND .................................................................................................................6 
2.1 
Study Disease(s) ................................................................................................................. 6 
2.2 
IND Agent ........................................................................................................................... 6 
2.3 
Rationale ............................................................................................................................. 7 
2.4 
Correlative Studies Background ......................................................................................... 8 
3. 
PARTICIPANT SELECTION .............................................................................................8 
3.1 
Eligibility Criteria ............................................................................................................... 9 
3.2 
Exclusion Criteria ............................................................................................................... 9 
3.3 
Screening, Recruitment, and Enrollment .......................................................................... 10 
4. 
REGISTRATION PROCEDURES ...................................................................................11 
4.1 
General Guidelines for DF/HCC and DF/PCC Institutions .............................................. 11 
4.2 
Registration Process for DF/HCC and DF/PCC Institutions ............................................ 11 
4.3 
General Guidelines for Other Investigative Sites ............................................................. 12 
4.4 
Registration Process for Other Investigative Sites ............................................................ 12 
5. 
TREATMENT AND/OR IMAGING PLAN .....................................................................12 
5.1 
Criteria and Process for Unblinding ................................................................................. 12 
5.2 
Treatment Regimen ........................................................................................................... 12 
5.3 
Pre-Treatment Criteria ...................................................................................................... 14 
5.4 
Agent Administration........................................................................................................ 14 
5.5 
General Concomitant Medication and Supportive Care Guidelines ................................. 15 
5.6 
Criteria for Taking a Participant Off Protocol Therapy .................................................... 16 
5.7 
Duration of Follow Up ...................................................................................................... 17 
5.8 
Criteria for Taking a Participant Off Study ...................................................................... 17 
5.9 
Study Stopping Rules ........................................................................................................ 18 
6. 
DOSING DELAYS/DOSE MODIFICATIONS ...............................................................18 
7. 
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS ............................18 
7.1 
Adverse Event List(s) for LY SARM ............................................................................... 19 
7.2 
Adverse Event Characteristics .......................................................................................... 19 
7.3 
Expedited Adverse Event Reporting ................................................................................. 19 
7.4 
Expedited Reporting to the Food and Drug Administration (FDA) ................................. 20 
7.5 
Expedited Reporting to Hospital Risk Management ......................................................... 20 
7.6 
Routine Adverse Event Reporting .................................................................................... 20 
8. 
PHARMACEUTICAL INFORMATION ..........................................................................21 
8.1 
LY SARM ......................................................................................................................... 21 
8.2 
Placebo .............................................................................................................................. 23 
9. 
STUDY CALENDAR .......................................................................................................24 
10. 
MEASUREMENT OF EFFECT........................................................................................26 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 02/05/2019 
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10.1 
Primary Outcome .............................................................................................................. 26 
10.2 
Secondary outcomes ......................................................................................................... 26 
11. 
DATA REPORTING / REGULATORY REQUIREMENTS ...........................................27  
11.1 
Data Reporting .................................................................................................................. 27 
11.2 
Data Safety Monitoring..................................................................................................... 28 
11.3 
Transmission of DSMB Recommendations and Summary Reports of Adverse Events to IRBs ... 28 
11.4 
Transmission of Summary of Closed Deliberations to the NINR Staff ............................ 28 
11.5 
Protecting the Confidentiality of Participant Data ............................................................ 28 
11.6 
Multicenter Guidelines...................................................................................................... 28 
11.7 
Collaborative Agreements Language ................................................................................ 28 
12. 
STATISTICAL CONSIDERATIONS...............................................................................28 
12.1 
Descriptive Analyses ........................................................................................................ 29 
12.2 
Compliance Analysis ........................................................................................................ 29 
12.3 
Analytic plan ..................................................................................................................... 29 
12.4 
Missing data ...................................................................................................................... 30 
12.5 
Sample Size Estimates and Power Considerations ........................................................... 30 
12.6 
DATA MANAGEMENT.................................................................................................. 31 
12.7 
Sample Size, Accrual Rate and Study Duration ............................................................... 32 
12.8 
Stratification Factors ......................................................................................................... 33 
12.9 
Interim Monitoring Plan ................................................................................................... 33 
12.10 Analysis of Primary Endpoints ......................................................................................... 33 
12.11 Analysis of Secondary Endpoints ..................................................................................... 33 
12.12 Reporting and Exclusions ................................................................................................. 33 
12.13 Evaluation of Toxicity ...................................................................................................... 33 
12.14 Evaluation of the Primary Efficacy Endpoint ................................................................... 33 
13. 
PUBLICATION PLAN .....................................................................................................33 
REFERENCES ..............................................................................................................................34 
APPENDIX A ................................................................................................................................53 
APPENDIX B ................................................................................................................................66 
APPENDIX C ................................................................................................................................71 
 
 
 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 02/05/2019 
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1. OBJECTIVES 
 
Androgen deficiency is common and associated with bothersome symptoms of sexual dysfunction, physical 
dysfunction, and fatigue in men with organ-localized prostate cancer who have undergone radical 
prostatectomy and have undetectable PSA levels for 2 or more years after their surgery. LY2452473 (LY 
SARM), a highly selective SARM, is particularly attractive for the treatment of symptoms of androgen 
deficiency in these patients because it displays agonist activities on sexual function and muscle but 
antagonist activity in the prostate in preclinical models and in human trials of up to 6 months duration. Our 
overall objective is to conduct a double-blind, placebo-controlled, parallel group, randomized dose ranging 
trial to determine the efficacy and safety of a SARM in improving the symptoms of androgen deficiency 
(sexual symptoms, fatigue/low vitality, and physical dysfunction) in men with prostate cancer who have 
undergone radical prostatectomy for organ-localized prostate cancer (pT2,N0,M0), Gleason score < 7 (3+4) 
, who have undetectable PSA (<0.1 ng/mL using a sensitive PSA assay) for > 2 years after radical 
prostatectomy, and who have androgen deficiency. In addition to demonstrating its safety, our first aim is to 
compare  0, 1,5 or 15 mg of LY SARM in men, who have undergone radical prostatectomy for organ-
localized prostate cancer, have symptomatic androgen deficiency and very low risk of disease recurrence, 
with regard to sexual function (sexual activity score, sexual desire, erectile function, distress and sexual life 
quality). The second aim is to compare the effects of 0, 1, 5 or 15 mg of SARM on fatigue, well-being and 
affectivity balance, and disease-specific quality of life. Our third aim is to determine whether SARM 
administration improves muscle mass and strength, and self-reported and performance-based measures of 
physical function, and aerobic capacity (VO2max , VO2 peak, and lactate threshold)more than placebo.   
 
1.1 
Study Design 
 
This will be a staged phase IIA randomized, placebo-controlled, parallel group, double blind trial in men, 19 
years of age or older, who have undergone radical prostatectomy for organ-localized prostate cancer, have 
low testosterone levels and associated symptoms, and are deemed to be at low risk of recurrence. At the end,  
114 subjects will have been randomized to placebo (n=36), 1 mg (n=28), 5 mg (n=36), and 15 mg (n=14) 
doses.  A target sample size of 114participants from three trial sites will have 90% power to test the primary 
hypothesis. 
 
1.2 
Primary Objectives 
 
Our overall objective is to conduct a double-blind, placebo-controlled, parallel group, randomized dose 
ranging trial to determine the efficacy and safety of a SARM in improving the symptoms of androgen 
deficiency (sexual symptoms, fatigue/low vitality, and physical dysfunction) in men with prostate cancer 
who have undergone radical prostatectomy for organ-localized prostate cancer (pT2,N0,M0), Gleason score 
<7 (3+4) who have undetectable PSA (<0.1 ng/mL using a sensitive PSA assay) for > 2 years after radical 
prostatectomy, and who have androgen deficiency. In addition to demonstrating its safety, our first aim is to 
compare  0, 1, 5 or 15 mg of LY SARM in men, who have undergone radical prostatectomy for organ-
localized prostate cancer, have symptomatic androgen deficiency and very low risk of disease recurrence, 
with regard to sexual function (sexual activity score, sexual desire, erectile function, distress and sexual life 
quality).  
 
1.3 
Secondary Objectives 
 
• To compare the effects of 0, 1, 5 or 15 mg of SARM on fatigue, well-being and affectivity balance, and 
disease-specific quality of life.  


NCI Protocol #: Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 02/05/2019 
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• To determine whether SARM administration improves muscle mass and strength, and self-reported and 
performance-based measures of physical function, and aerobic capacity (VO2max , VO2 peak, and lactate 
threshold)more than placebo.   
 
2. BACKGROUND 
 
2.1 
Study Disease(s) 
 
Prostate cancer is the most common malignancy in American men, accounting for 29% of all diagnosed 
cancers and approximately 13% of all cancer deaths; its incidence is on the rise, partly due to increased 
screening with PSA52. In 2010, approximately 217,730 new cases of prostate cancer were diagnosed in the 
United States, and there were 32,050 deaths related to prostate cancer53. The majority of these men have 
low-grade, organ-confined prostate cancer and excellent prospects of long term survival54-57. Substantial 
improvement in survival in men with prostate cancer has focused attention on the high prevalence of sexual 
dysfunction, physical dysfunction, and low vitality in these men11-25, 58-61, which are important contributors 
to poor quality of life among these patients11-18, 23. The pathophysiology of these symptoms - sexual 
dysfunction, fatigue/low vitality, and depressed mood - after radical prostatectomy is multifactorial, but 
androgen deficiency is an important remediable contributor to these symptoms.  
 
2.2 
IND Agent 
 
Preclinical and Phase I and II Experience with LY SARM 
LY SARM, an oral, tissue-specific SARM, displays agonist effects on sexual function, anabolic effects on the 
muscle and bone, with antagonist effect on the prostate. Because of its AR antagonist properties on the prostate, 
its application is also being explored for the treatment of benign prostatic hypertrophy and prostate cancer.  
There were no potentially serious or life threatening toxicities for LY SARM in preclinical toxicology 
studies. LY SARM-induced pharmacological effects consistent with androgen receptor agonism in repeat dose 
toxicological studies. The primary adverse effects in rats and dogs involved changes in reproductive organs 
consistent with the expected effects of an androgen receptor agonist. Safety pharmacology studies of up to 6-
month duration indicate a high safety margin for the drug.  In toxicological studies, LY SARM demonstrated no 
drug-related effects at doses up to 1000 mg/kg in gastrointestinal (GI), renal, pulmonary, and cardiovascular 
function studies.  
In gonadectomized rodent model, LY SARM demonstrated anabolic effects on muscle and 
osteoanabolic properties on bone mass and biomechanical strength at doses that had no significant effect on 
prostate and seminal vesicles. Its nearly complete selectivity for AR has been demonstrated in preclinical 
models, and in phase I and II human trials. LY SARM has demonstrated agonistic activity on sexual function 
(stimulated mating behavior, sexual arousal, NOS, and PDE5 expression).  
LY SARM has shown high degree of tissue selectivity. In a canine model, the administration of LY 
SARM was associated with a 40% reduction of prostate volume, consistent with its AR antagonist properties in 
the prostate. In mice bearing explants of AR+ prostate cancer, LY SARM suppressed the growth of explants.   


NCI Protocol #: Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 02/05/2019 
7 
 
LY SARM has undergone testing in multiple phase I and II trials, which have established its safety in 
doses of up to 75 mg daily in humans. Clinical trials of up to 6-month duration have been conducted. In phase I 
dose ranging studies of 21 day duration (figure 1), LY SARM increased muscle volume by pQCT (figure 1, left 
panel) and suppressed PSA levels (figure 1, right panel), and exhibited no grade 2 or 3 toxicity.  LY SARM 
shares with other oral androgens the property of lowering HDL cholesterol as well as total cholesterol modestly. 
These data demonstrate LY SARM’s safety and tissue selectivity; it is an agonist on the skeletal muscle and an 
antagonist on the prostate. Consequently, unlike testosterone or other androgens, LY SARM would not be 
expected to promote the growth of prostate cancer. This is analogous to the use of tamoxifen, a selective 
estrogen receptor modulator (SERM), which acts as an agonist on the uterus and bone but as an antagonist in 
the breast tissue.  
 
 
 
 
 
 
In phase II efficacy trials of 12 week duration, 5 mg LY SARM daily was demonstrated to be safe 
and increased lean body mass by ~1.5 kg and muscle volume (by CT) by 4-6%, and significantly 
reduced fat mass in line with other SARMs and replacement doses of testosterone.  There was an 
expected decrease in total cholesterol and HDL cholesterol. No grade 2 or 3 toxicity was recorded.     
 
 
 
Several other SARM molecules have undergone phase I and II trials and one has undergone a 
phase III trial in patients with cancer cachexia. These trials have shown these SARM molecules to be 
generally safe. The class effects include a modest reversible decrease in total and HDL cholesterol, 
and mild transaminase elevations in a small fraction of subjects. 
 
2.3 
Rationale 
 
-0.6
-0.5
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
0.4
0 mg
1 mg
5 mg
15 mg
25 mg
Change from Baseline (ug/L
ay
8
S
a es o
y
4000
-3000
-2000
-1000
0
1000
2000
3000
4000
0 mg
1 mg
5 mg
Lean Body Mass Change (g)
Females
Males
Lean muscle 
with DEXA
Figure 1. Dose ranging study of LY2452473 in healthy volunteers demonstrates dose-dependent 
gains in muscle cross-sectional area measured by quantitative CT scan of thigh muscles (left panel) 
and a dose-related lowering of PSA levels (right panel). These data demonstrate LY SARM’s tissue 
selectivity; it is an agonist on the skeletal muscle and an antagonist on the prostate.  
Figure 2. In a phase II trial, healthy men and 
women were treated with 0, 1 or 5 mg SARM 
daily for 6 months.  Dose-dependent gains in 
LBM, measured by DXA are shown.  
-8
-6
-4
-2
0
2
4
6
8
10
12
0 mg
5 mg
25 mg
Muscle Area Change (cm2)
Left Side
Right Side
pQCT calf muscle area change


NCI Protocol #: Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 02/05/2019 
8 
 
Androgen deficiency in men who have undergone prostatectomy for organ-localized prostate cancer is 
common1-12 and often associated with bothersome symptoms13-17 and other adverse health effects that 
contribute to poor health-related quality of life (HRQOL)18-23. Improved survival of men with prostate 
cancer has focused attention on strategies to treat symptoms and improve the overall HRQOL18-23.  
Androgen signaling plays an important role in prostate cancer growth24-31. Testosterone therapy promotes 
the growth of metastatic prostate cancer and androgen deprivation causes regression of metastatic prostate 
cancer32-34. Not surprisingly, the expert guidelines of many professional societies list prostate cancer as a 
contraindication for androgen supplementation24-25. This proscriptive guidance does not fully reflect our 
new understanding of the complex relationship between testosterone and prostate cancer1-5, 34-42. 
Epidemiologic studies have revealed no consistent relationship between testosterone levels and prostate 
cancer risk34-40.  
Several elegant studies have found little or no effect of testosterone administration on intraprostatic 
androgen concentrations or on androgen-dependent gene expression in the prostate41-42. Several open-label 
trials of testosterone have reported very low rates of disease recurrence in men with prostate cancer who 
have undergone radical prostatectomy1-11,43-44. Consequently, testosterone use among men who have 
undergone radical prostatectomy has been increasing, even though neither the safety nor the efficacy of 
testosterone therapy in improving outcomes has been established in these patients. A confluence of 
historical factors – improved survival of men with prostate cancer, a growing recognition of the importance 
of symptom control in the lives of cancer survivors, increasing off-label use of testosterone in patients who 
have undergone radical prostatectomy, and accumulation of clinical experience from nonrandomized trials - 
has highlighted the need for randomized trials of androgen therapy in men with a history of prostate cancer, 
particularly for those, who experience symptoms of androgen deficiency – sexual dysfunction, fatigue, and 
physical dysfunction.  
Selective androgen receptor modulators (SARMs) are a new class of ligands that displays tissue-selective 
anabolic activity in the muscle, anti-resorptive and anabolic activity in bone, androgenic activity in 
maintaining sexual behavior, and robust selectivity for muscle versus prostate45-51. LY2452473 (LY 
SARM), a highly selective SARM, is particularly attractive in men with prostate cancer because it displays 
agonist activity on sexual function and muscle but antagonist activity in the prostate in preclinical models 
and in human trials of up to 6-month duration. Unlike testosterone, LY SARM induces prostate atrophy in 
dogs and lowers PSA in men. Consequently, the administration of Lilly SARM would not be expected to 
increase the risk of disease recurrence; it is, in fact, possible that it may reduce prostate cancer recurrence 
risk. This is analogous to the use of tamoxifen in women with breast cancer; tamoxifen, a selective estrogen 
receptor modulator (SERM), is an estrogen antagonist in the breast but an agonist on the endometrium and 
bone.  Thus, we believe that the clinical application of such a selective, prostate sparing SARM would be a 
very major scientific breakthrough. 
 
2.4 
Correlative Studies Background 
 
Not applicable 
 
3. PARTICIPANT SELECTION 
 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 02/05/2019 
9 
 
This will be a phase IIA randomized, placebo-controlled, parallel group, double blind trial in men, 19 years 
of age or older, who have undergone radical prostatectomy for organ-localized prostate cancer, have low 
testosterone levels and associated symptoms, and are deemed to be at low risk of recurrence. At the end, a 
total of 135 subjects will have been randomized; 36, 28, 26 and 14 men to placebo, 1 mg, 5 mg and 15 mg 
doses, respectively.   
 
3.1 
Eligibility Criteria 
 
3.1.1 Age 19 years or older.   
3.1.2 Prostate cancer, with organ-localized disease with very low risk of disease recurrence, as indicated by 
Stage pT2, N0, M0 lesions(if 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 of 7 (3+4) 
or less, and preoperative PSA<10 ng/ml.The rationale for selecting men with these criteria is that this 
group of men has <0.5% disease recurrence rate over ten years [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]. 
3.1.3 Stable and undetectable PSA level (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  
3.1.4 Serum testosterone, measured by LC-MS/MS, <300 ng/dL and/or calculated free testosterone ≤70 
pg/mL.  
3.1.5 Self-reported sexual dysfunction (DISF-M-II score ≤20 in the sexual desire domain), and/or fatigue 
(FACIT-F score<30), or physical dysfunction (self-reported difficulty in walking a 1/4 mile or climbing 
two flights of stairs, and short physical performance battery score (SPPB) between 4 to 9).  
3.1.6 Ability to understand and willingness to sign a written informed consent document. 
3.1.7 Agreeing 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. The effects of LY2452473 
(LY SARM) on the developing human fetus are unknown.  For this reason and because SARM agents are 
known to be teratogenic, women of child-bearing potential and men must agree to use adequate 
contraception (hormonal or barrier method of birth control, or abstinence) prior to study entry and for 
the duration of study participation.  Should a woman become pregnant or suspect she is pregnant while 
her partner is participating in this study, she should inform her treating physician immediately.   
 
3.2 
Exclusion Criteria 
3.2.1 Men who have undergone radiation therapy alone will be excluded because defining biochemical 
recurrence can be difficult in these men due to fluctuating PSA levels.  
3.2.2 Prior or current androgen deprivation therapy 
3.2.3 Hematocrit > 50% 
3.2.4 Severe untreated sleep apnea (treatment is defined as therapy with CPAP, BiPAP, ASV, or other 
positive air pressure device) 
3.2.5 Uncontrolled heart failure as defined by New York Heart Association(NYHA)class 3 or 4 
3.2.6 History of HIV (protease inhibitors can have interaction with the SARM)  
3.2.7 Myocardial infarction, acute coronary syndrome, revascularization surgery, or stroke within 3 months 
3.2.8 Serum creatinine >2.5 mg/dL; ALT or AST outside normal limits for the lab being used 
3.2.9 Hemoglobin A1c >7.5% or diabetes requiring insulin therapy 
3.2.10 Body mass index (BMI) >40 kg/m2 
3.2.11 Major psychiatric disorder, such as schizophrenia, bipolar disorder, or untreated depression (treatment 
for depression is defined as current therapy with antidepressant medication or cognitive behavioral 
therapy (CBT)). 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 02/05/2019 
10 
 
3.2.12 Use of any of the following medications within the past 6 months: testosterone, DHEA, estrogens, 
GnRH analogs, antiandrogens, spironolactone, ketoconazole, rhGH, megesterol acetate, prednisone 20 
mg daily or equivalent doses of other glucocorticoids for more than two weeks 
3.2.13 Use of any of the following medications within the past 6 months: Clarithromycin, telithromycin, 
chloramphenicol, itraconazole, nefazodone, cobicistat. 
 
3.2.14 Use of the following treatments for erectile dysfunction (ED): penile implants, vacuum pump devices,  
intracavernosal injections 
 
3.3 
Screening, Recruitment, and Enrollment 
 
Participant Screening 
 
Participants identified through institutional urology groups will be prescreened using medical records to 
determine if they are potentially eligible.  The potentially eligible subjects will be contacted for further 
screening.  If participants are interested, verbal consent will be obtained via an IRB approved script prior to 
administering a telephone screening with a standardized script and questionnaire.  
 
At the Brigham and Women’s Hospital site (BWH), use of EPIC and at the Beth Israel Deaconess Medical 
Center (BIDMC) subject referring site, use of the PIMS will be utilized to identify potential study subjects. 
 
After obtaining consent, to determine eligibility, a directed medical history will be obtained and blood 
count, chemistries, total and free testosterone, and PSA will be measured. The pathological stage and 
pretreatment PSA level will be obtained from medical records. Subjects meeting eligibility criteria will be 
scheduled for baseline studies. 
 
Participant Recruitment and Enrollment 
Participants will be enrolled from the urology clinics at BWH and BIDMC (subject referring site only), 
from the oncology clinics at Dana Farber Cancer Center at the Boston site, from the Brady Urological 
Research Institute at the Johns Hopkins Medical Institute at the Baltimore site, and from the urology clinics 
and from the general community at the UFL site. At BWH we also will employ direct mailings to patients 
with prostate cancer identified through the institutional urology groups and medical records, institutional 
portals such as the Research Patient Data Registry (RPDR) and Research Study Volunteer Program (RSVP), 
whose use for subject recruitment has been IRB-approved.  
 
RPDR is a centralized clinical data registry, or data warehouse. The RPDR gathers data from various 
hospital legacy systems and stores it in one place. The RPDR has two related but separate functions. First, 
an online Query Tool provides users with aggregate numbers of patients with user-defined characteristics 
such as diagnoses, procedures and/or laboratory results. Patient identifiers are not available at this function 
level. Secondly, the RPDR Data Acquisition Engine (DAE) allows the user to receive more detailed medical 
record information about the queried patients. 
 
Research Study Volunteer Program (RSVP for Health) is a database that allows researchers to search by 
disease area, age, race, gender, and ethnicity. Once the researcher identifies the population they'd like to 
contact, RSVP for Health sends potential volunteers an email containing the IRB-approved study 
announcement and prepares letters for those who wish to be contacted through US mail. The identity of 
potential volunteers is maintained until they choose to contact the research team.  
 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 02/05/2019 
11 
 
4. REGISTRATION PROCEDURES 
 
4.1 
General Guidelines for DF/HCC and DF/PCC Institutions 
 
Institutions will register eligible participants with the DF/HCC Office of Data Quality (ODQ) central 
registration system. Registrations must occur prior to the initiation of protocol therapy. Any participant not 
registered to the protocol before protocol therapy begins will be considered ineligible and registration will 
be denied. 
 
An investigator will confirm eligibility criteria and a member of the study team will complete the (ODQ) 
protocol-specific eligibility checklist. 
 
Patients are randomized at the time of registration, and treatment assignment will be communicated to each 
respective site investigational pharmacy so that the proper treatment assignment can be allocated to each 
patient. The biostatistician will provide the (ODQ) Registrars with the treatment assignment list prior to 
study activation. At the time of registration, the confirmation of registration would be sent to the study team, 
while the treatment assignment would be sent directly to pharmacy. 
 
Following registration, participants may begin protocol therapy. Issues that would cause treatment delays 
should be discussed with the Overall Principal Investigator (PI). Notify the (ODQ) Registrar of registration 
cancellations as soon as possible. 
 
4.2 
Registration Process for DF/HCC and DF/PCC Institutions 
 
The (ODQ) registration staff is accessible on Monday through Friday, from 8:00 AM to 5:00 PM Eastern 
Standard Time. In emergency situations when a participant must begin protocol therapy during off-hours or 
holidays, call the (ODQ) registration line at 617-632-3761 and follow the instructions for registering 
participants after hours. 
 
The registration procedures are as follows: 
 
• Obtain written informed consent from the participant prior to the performance of any protocol 
specific procedures or assessments.  
 
• Complete the (ODQ) protocol-specific eligibility checklist using the eligibility assessment 
documented in the participant’s medical record and/or research chart. To be eligible for registration 
to the protocol, the participant must meet all inclusion and exclusion criterion as described in 
the protocol and reflected on the eligibility checklist. 
 
• Reminder: Confirm eligibility for ancillary studies at the same time as eligibility for a treatment 
protocol. Registration to both treatment and ancillary protocols will not be completed if eligibility 
requirements are not met for all studies.  
 
• Fax the eligibility checklist(s) and all pages of the consent form(s) to the (ODQ) at 617-632-2295. 
For Phase I protocols, attach participant dose level assignment confirmation from the sponsor. 
 
• The (ODQ) Registrar will (a) review the eligibility checklist, (b) register the participant on the 
protocol, and (c) randomize the participant when applicable. 


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• An email confirmation of the registration will be sent to the Overall PI, study coordinator(s) from the 
Lead Site, treating investigator and registering person immediately following the registration. 
Treatment assignment will be sent directly to pharmacy via fax. 
 
4.3 
General Guidelines for Other Investigative Sites 
 
Eligible participants will be entered in to the study centrally at the Brigham and Women’s Hospital by the 
Study Coordinator.   
 
Following registration, participants should begin protocol therapy within 5 days. Issues that would cause 
treatment delays should be discussed with the Overall PI.  The Study Coordinator should be notified of 
cancellations as soon as possible. 
 
Research activities for participants originating from Beth Israel Deaconess Medical Center will occur at 
Brigham and Women’s Hospital and will be registered by the Brigham and Women’s Hospital study 
coordinator.  Participants referred from BIDMC will continue their routine clinical care outside of the 
research protocol. 
 
4.4 
Registration Process for Other Investigative Sites 
 
The registration process for other investigative sites is located in the DSMP in section 15.7.1. 
 
 
5. TREATMENT AND/OR IMAGING PLAN 
 
5.1 
Criteria and Process for Unblinding 
In both urgent and non-urgent situations: Only the trial’s Data and Safety Monitoring Board is authorized to 
request unblinding of participant-level intervention assignment in one or more subjects in non-urgent 
situations should a safety concern so warrants. In urgent situations, the Principal Investigator may direct the 
study physician to unblind the intervention assignment should this information be deemed necessary by the 
patient’s primary care provider or emergency department clinician to manage an urgent medical condition.  
 
5.2 
Treatment Regimen 
 
LY SARM or Placebo will be administered daily for a period of 12 weeks.  LY SARM or Placebo will be 
dispensed to the subject in pill form in four week supplies.  The drug or placebo will be dispensed at 
baseline (Visit 2b), week 4, and week8.   Reported adverse events and potential risks are described in 
Section 7.  No investigational or prohibited therapies other than those described below may be administered 
during the course of this study. 
 
The study medication should be taken daily in the morning on an empty stomach at about the same time 
each day.  The medication should be swallowed whole with water.  The bottle containing the medication 
should be stored at room temperature.  The medication does not need refrigeration.  If the subject vomits 
after taking the dose and sees the study drug capsule in the emesis, he should wait for an hour and then 
retake a new capsule of the medication.  If the subject does not see the study drug capsule in the emesis, he 
should not take another dose.  If the subject forgets to take the drug in the morning and remembers it later 
during the day including bedtime, he should go ahead and take the drug for that day as soon as it is 


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remembered.  The medication is best taken in the morning on a fasting stomach at least 30 minutes before 
any meal, although if the participant forgets to take a dose but remembers later in the day, he should take the 
medication at that time. It may not be practical for many individuals, who are employed, to fast during the 
day.   Breakfast can be eaten 30 minutes or later after taking the study medication.  There are no prohibited 
foods.  The drug is supplied in capsules. At one time, subjects will be provided sufficient medicine for a 
period of 4 weeks. At the end of the 4 week period, they should return any unused medication to the study 
staff along with the filled–in drug diary.  
 
We will measure compliance using medication logs and pill counts, which provide the best trade-off 
between accuracy and cost283-284. The participant will be requested to maintain a medication diary of each 
dose of medication that will be provided to them by the study staff.  The medication diary will be returned 
to clinic staff at the end of each cycle.  Furthermore, pill counts will be done to measure compliance.  
Medication logs will be collected and unused pills will be counted. Adherence will be assessed as number of 
pills used divided by number of days.  
 
1. LY2452473 is supplied as an oral capsule drug product in size 2 opaque white gelatin capsules. Each 
capsule contains 1 mg, 5 mg or 15 mg of LY2452473 and the inactive ingredients pregelatinized starch 
and dimethicone. LY2452473 is intended to be supplied for the proposed clinical trial as capsules 
packaged in 30 count white, induction sealed high density polyethylene (HDPE) bottles with child-
resistant closures.  
2. The drug product will be packaged and supplied to the IDS by Catalent Pharma Solutions, Kansas 
City, Missouri, USA. 
3. The drug product will be stored at room temperature (25°C) with allowable excursions between 15 - 
30°C. 
4. The drug will be dispensed by the IDS in an amount sufficient for 30 days.  
5. The IDS will release the study medication to an authorized study staff upon receipt of a prescription 
written and signed by a study clinician. The study staff will dispense the study medication to the 
participant in accordance with the study protocol along with a set of written instructions on how to 
take the medication. 
6. The study staff will retrieve the unused medication from the participant for the purpose of assessing 
adherence.    
 
Subject Intervention  
The study intervention includes placebo and three doses of LY SARM (1, 5 and 15 mg daily). Subjects who 
meet the eligibility criteria, will be randomized, to either placebo, 1 mg SARM, 5 mg SARM or 15 mg 
SARM daily.  The subject assignment will be based on the randomization tables, using permuted blocks 
with varying blocks sizes. Subjects will be stratified by age (19-50 and >50) and use of phosphodiesterase 5 
inhibitors (PDEIs); PDEIs may influence sexual function (and mood and HRQOL) independently228-231. 
Stratification variables will be included as covariates in analyses. 
 
SARM Doses and Regimen 
The participants will be randomly assigned to receive either placebo, 1 mg LY SARM, 5 mg LY SARM, or 
15 mg LY SARM daily for 12 weeks. In phase II trials of up to 6-month duration, these doses were safe and 
effective in increasing lean body mass. 5 mg dose increased fat-free mass by an average 1.5 kg in men.  
 


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Intervention Duration 
The effects of SARM as well as testosterone on sexual function, muscle mass, strength, well being and 
mood become apparent within 3 months48, 171-177; PSA levels rise within 3-4 weeks and reach a plateau by 
12-weeks109-110. Thus, 3-month duration will be sufficient to detect meaningful changes in outcomes and 
PSA. 
 
Phosphodiesterase Inhibitors Use 
PDEIs may independently affect sexual function (and HRQOL)226-231. To minimize confounding due to 
PDEI use, we will stratify randomization based on PDEI use. PDEI use will be used as a covariate in 
analyses. 
 
5.3 
Pre-Treatment Criteria 
 
Prior to subject’s enrollment, the study coordinators will explain the purpose of the study, the study 
procedures, and potential risks and benefits of participation in this trial, and answer any questions. The 
subjects will be asked to sign the IRB-approved consent form. To determine eligibility, a directed medical 
history will be obtained, and blood count, chemistries, total and free testosterone, and PSA will be 
measured. The pathological stage and pretreatment PSA level will be obtained from medical records. 
Subjects meeting eligibility criteria will be scheduled for baseline studies. Subjects, who meet the eligibility 
criteria will undergo baseline studies, which include baseline complete blood count, blood chemistries, and 
baseline assessment of physical function, sexual function, fatigue, as described in the protocol. The subjects 
who are eligible and have completed the baseline assessments will be randomized.  
 
5.4 
Agent Administration 
 
Administration –The dose will be 0 mg (placebo), 1 mg, 5 mg, or 15 mg of LY SARM depending upon 
which study group that the subject is randomly assigned to.  LY SARM or Placebo will be taken orally, 
once per day.  The intervention period is twelve weeks.  Subjects will be given the drug in four week 
supplies at baseline (Visit 2b), week 4 and week 8.  Their compliance will be measured by pill counts at 
week 4, week 8 and week 12.  In addition, medication logs will be given to subjects. 
 
Protocol specific procedures –A study physician will obtain consent. The safety laboratory results will be 
reviewed by one of the study physicians. During each visit, a research coordinator will ask the participants 
about any adverse events. A study clinician will perform a physical examination at screening and during 
weeks 6 and 12.A study physician will be available if an issue arises at the study visits with the research 
coordinator. 
 
The research staff will take interim status during baseline, weeks 2, 4, 6, 8, and 12.  During interim status, 
the subject will be asked questions about any changes in health or medication.  Blood tests will be done at 
screening, baseline, as well as during weeks 2, 4, 6, and 12.  DXA and strength assessments will be 
performed at baseline and during week 12.   
 
Infusion Reactions – Subjects will be monitored for PSA level, hematocrit, hemoglobin, HDL level, and 
liver enzymes. 
 
Sometimes due to scheduling issues, staff availability, inclement weather or subject availability, we may ask 
the subject to return to our research clinic in order to complete a visit or a specific procedure at a different 
time or day. This may affect some of the procedures at any visit. In case of such an event, if the subject 


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parks in our valet parking area, their parking will be validated.  
 
The investigators may omit any strength assessments (muscle performance or physical function procedures) 
for safety purposes. In such instances, the investigators will determine which procedures will be omitted and 
this will be documented in the subject’s study file.   
 
Caregiver Precautions -  
Nurse’s/ Study Staff’s Instructions to Patients  
1. The medication should not be dispensed by a woman who is pregnant or may become pregnant. 
Women who are pregnant or may become pregnant must use caution when cleaning up vomited 
matter. 
2. Please, take your study medication daily in the morning on an empty stomach at about the same time 
each day. 
3. The medication should be swallowed whole with water. 
4. The bottle containing the medication should be stored at room temperature.  The medication does not 
need refrigeration. 
5. If you vomit after taking the dose, please wait for an hour and then retake the medication. 
6. If you forget to take your medication in the morning and remember it later during the day including 
bedtime, please go ahead and take your medication for that day as soon as you remember it. If you 
forget to take your dose in the morning after an overnight fast, please do not eat or drink anything 
(other than water) for two hours prior to taking the drug.  Once you have taken the drug, please do 
not eat or drink anything other than water for 30 minutes. After that, you may resume your regular 
diet. 
7. The medication is best taken in the morning on a fasting stomach and continue fasting for at least 30 
minutes before any meal. 
8. You can eat your breakfast 30 minutes or later after taking the study medication.  
9. There are no prohibited foods.  
10. Please record the medication in the drug diary as soon as you take the medication. The drug diary 
will be provided to you by the study staff. 
11. The drug is supplied in capsules. At one time, you will be provided sufficient medicine for a period 
of 4 weeks. At the end of the 4 week period, please return any unused medication to the study staff 
along with the filled–in drug diary.  
 
5.4.1 IND agent 
The IND agent is discussed in detail in Section 8. 
 
5.4.2 Other Agent(s) 
N/A 
 
5.4.3 Other Modality(ies) or Procedures 
N/A 
 
5.4.4 Investigational Imaging Agent Administration 
N/A 
 
5.5 
General Concomitant Medication and Supportive Care Guidelines 
 


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The case report form will be developed to capture the concurrent use of all other drugs, over-the-counter 
medications, or alternative therapies.   
 
• The use of the following medications if not allowed during the course of the study: testosterone, 
DHEA, estrogens, GnRH analogs, antiandrogens, spironolactone, ketoconazole, rhGH, megesterol 
acetate, prednisone 20 mg daily or equivalent doses of other glucocorticoids 
 
5.6 
Criteria for Taking a Participant Off Protocol Therapy 
 
Treatment will continue for 12 weeks or until one of the following criteria applies: 
 
• An increase in PSA to 0.2 ng/mL or higher, if confirmed by a repeated test, will result in treatment 
discontinuation and referral to a urologist. An increase in PSA will be confirmed by a repeat test which 
may result in removal from the study. The study team will contact the participant within a week after 
test result becomes available for scheduling the repeat test if the first test revealed an increase in PSA. 
If the repeat test confirms the elevation, the intervention will be stopped and the participant will 
continue to be followed in the study per intent-treat analytical design. The study medication will 
continue until the results of the repeated test become available. The participant will also be referred to 
a urologist, medical oncologist, or a primary care provider depending on the nature of the problem. If 
the repeat test does not confirm the elevation, the participant will continue in the study and have the 
next set of lab tests per study protocol. 
• Any other sign of disease recurrence (e.g., evidence of bone metastasis detected by the subject’s 
oncologist) 
• Myocardial infarction or stroke   
• Unacceptable adverse event(s) 
• Participant demonstrates an inability or unwillingness to comply with the oral medication regimen 
and/or documentation requirements 
• Participant decides to withdraw from the protocol therapy 
• General or specific changes in the participant's condition render the participant unacceptable for 
further treatment in the judgment of the treating investigator 
• Other DLTs include hematocrit increase above 54% and transaminase elevation above 1.25 times the 
upper limit of normal, confirmed by repeating these tests. An increase in hematocrit and transaminase 
will be confirmed by a repeat test which may result in removal from the study. The study team will 
contact the participant within a week after test result becomes available for scheduling the repeat test 
if the first test revealed an increase in hematocrit or transaminases. If the repeat test confirms the 
elevation, the intervention will be stopped and the participant will continue to be followed in the study 
per intent-treat analytical design. The study medication will continue until the results of the repeated 
test become available. The participant will also be referred to a urologist, medical oncologist, or a 
primary care provider depending on the nature of the problem. If the repeat test does not confirm the 


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elevation, the participant will continue in the study and have the next set of lab tests per study protocol. 
Any abnormal liver function test, defined by a value that is greater than 1.25 times the upper limit of 
normal, will also require a repeat blood test within 3-7 days, to confirm the result and observe the 
trend. If the participant’s levels do not exceed 1.25 times the upper limit of normal, they will continue 
on the study medication and transaminases will be monitored.  
 
 
Note that for an abnormal lab value to meet the DLT definition, the lab test must be repeated and the repeat 
test must confirm the elevation.  
 
If the participants experience a grade 4 non-hematological toxicity, the study medication will be stopped and 
the participant will be referred to his medical oncologist, urologist, or the primary care provider depending 
on the nature of the toxicity. However, study assessments will continue per study’s intent-to-treat design. 
 
Participants will be removed from the protocol therapy when any of these criteria apply.  The reason for 
removal from protocol therapy, and the date the participant was removed, will be documented in the case 
report form (CRF). Alternative care options will be discussed with the participant. 
 
A ODQ Treatment Ended/Off Study Form will be filled out when a participant is removed from protocol 
therapy. This form can be found on the ODQ website or obtained from the ODQ registration staff. The 
QACT Treatment Ended/Off Study Form will be completed by each site and then sent the Coordinating 
Center for all study participants. 
 
In the event of unusual or life-threatening complications, treating investigators must immediately notify the 
Overall PI, Shalender Bhasin, MD at 617-525-9040.  
 
5.7 
Duration of Follow Up 
 
The subjects who come off the study medication for disease recurrence or adverse events will be referred to 
their urologist or medical oncologist or primary care provider for further evaluation and treatment, 
depending on the nature of the problem. Because of the intent-to-treat analytical design, they will continue 
to be followed in the study for further study assessments per protocol. 
 
5.8 
Criteria for Taking a Participant Off Study 
 
Participants will be removed from study when any of the following criteria apply: 
• Lost to follow-up 
• Withdrawal of consent 
• Death 
Consistent with the intent-to-treat primary analytical strategy, we will encourage all participants, including 
those in whom the study medication is discontinued because of the reasons listed above, to continue with 
their follow-up study assessments.  
 
The reason for taking a participant off study, and the date the participant was removed, will be documented 
in the case report form (CRF). 
 


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A ODQ Treatment Ended/Off Study Form will be filled out when a participant comes off study. This form 
can be found on the ODQ website or obtained from the ODQ registration staff.  
 
The ODQ Treatment Ended/Off Study Form will be completed by each site and then sent to the 
Coordinating Center for all study participants. 
 
5.9 
Study Stopping Rules 
 
In light of the phase I and II trials data, we anticipate very low rates of grade II or III toxicity. The main 
reason for trial’s early termination would be unexpectedly high rates of PSA recurrence. By virtue of the 
eligibility criteria, this population should have very low recurrence rates (<0.5% over 5 years).  
 
Among the first 50 enrolled subjects, we assume that we should have about 16 in placebo and about 34 or so 
in the two SARM arms.   
 
In the control group, we expect a recurrence rate of <0.5% over 5 years (for the purpose of this calculation, we 
assumed a recurrence rate of 0.5% over 5 years). We will accept a difference of no more than 3 between the 
placebo and the   SARM arms in aggregate after 50 subjects have been randomized. If the PSA recurrence 
occurs in 3 or more cases in the two SARM arms in aggregate or 3 or more cases in any one SARM arm, the 
DSMB may stop the trial. The probability of a single recurrence is 0.005 (probability of 'not recurrent' is 
0.995 at 5 years). Thus, if the bar is set at 3 recurrences, the probability of making an error and stopping early 
when in fact there is no extra risk conferred by SARM is only 1 in 1250.   
 
At 4 or more recurrences, the chance of erroneous early stoppage is 1 in 25000, which seems large. Therefore, 
we submit that a difference of 3 recurrences between the placebo arm and the 2 SARM arms in aggregate is 
reasonable as a stopping rule that DSMB will consider in its decision. The DSMB has the discretion of 
stopping the trial for other reasons.  
 
6. DOSING DELAYS/DOSE MODIFICATIONS 
 
No dose modifications are allowed. Dose modification is not planned in the context of this double blind 
phase II randomized trial for several reasons. One aim of the trial is to assess the dose response relationship 
of dose with the study’s outcomes, which could be compromised if the dose adjustment were to occur. The 
study is blinded; dose adjustment may unblind the study. Also, the drug will be manufactured in either 1 
mg, 5 mg or 15 mg capsules. Therefore, we do not have any mechanism for administering intermediate 
doses.  Furthermore, based on the preclinical animal data, and phase I and II previous human studies, we 
anticipate very low frequency of DLT. Also, we do not have any previous data to guide rational dose 
adjustment. 
 
If the subject forgets to take one or more doses, he will be asked to record the missed doses in the 
medication log and re-initiate the usual daily dosing. Study staff will encourage all participants to take all 
the pills as specified in the protocol. We will also perform pill counts and use drug logs to monitor 
compliance. However, because of the intent-to-treat analytical plan, the participants will continue in the 
study for their assessments per protocol. 
 
7. ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS 
 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial.  The following list of 


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reported and/or potential AEs (Section 7.1) and the characteristics of an observed AE (Section 7.2) will 
determine whether the event requires expedited reporting in addition to routine reporting. 
 
7.1 
Adverse Event List(s) for LY SARM 
In previous phase I and II studies of LY SARM, the drug was well tolerated and no drug-related grade II or III 
toxicities were recorded. A modest decrease in total cholesterol and HDL cholesterol was noted, which is a 
class effect of oral androgens. There were no clinically significant changes in liver function. No significant 
changes in hemoglobin and hematocrit were noted. In phase I studies, a decrease in PSA was noted. The class 
effects of oral androgens and SARMs include a decrease in total and HDL cholesterol, increase in hematocrit 
(not observed with this SARM), and mild increases in AST and ALT. There may also be a risk of disease 
recurrence although that risk would be very small because of LY SARM’s selectivity. 
 
7.2 
Adverse Event Characteristics 
 
• CTCAE term (AE description) and grade:  The descriptions and grading scales found in the revised 
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE 
reporting.  All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.  A 
copy of the CTCAE version 4.0 can be downloaded from the CTEP web site 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
 
• For expedited reporting purposes only:   
- 
AEs for the agent(s) that are listed above should be reported only if the adverse event varies in 
nature, intensity or frequency from the expected toxicity information which is provided. 
- 
Other AEs for the protocol that do not require expedited reporting are outlined in the next 
section(Expedited Adverse Event Reporting) under the sub-heading of Protocol-Specific Expedited 
Adverse Event Reporting Exclusions. 
 
• Attribution of the AE: 
- 
Definite – The AE is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE may be related to the study treatment. 
- 
Unlikely – The AE is doubtfully related to the study treatment. 
- 
Unrelated – The AE is clearly NOT related to the study treatment. 
 
7.3 
Expedited Adverse Event Reporting 
 
7.3.1 Investigators must report to the Overall PI any serious adverse event (SAE) that occurs after the initial 
dose of study treatment, during treatment, or within 30 days of the last dose of treatment on the local 
institutional SAE form.  
 
7.3.2 For multi-institution studies where a DF/HCC investigator is serving as the Overall Principal 
Investigator, each participating institution must abide by the reporting requirements set by the DF/HCC. 
This applies to any medical event equivalent to an unexpected grade 2 or 3 with a possible, probable or 
definite attribution, unexpected grade 4 toxicities, and grade 5 (death) regardless of study phase or 
attribution. 
 
7.3.3 
DF/HCC Expedited Reporting Guidelines 
 


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Investigative sites within DF/HCC and DF/PCC will report SAEs directly to the DFCI Office for Human 
Research Studies (OHRS) per the DFCI IRB reporting policy. 
 
Other investigative sites will report SAEs to their respective IRB according to the local IRB’s policies 
and procedures in reporting adverse events. A copy of the submitted institutional SAE form will be 
forwarded to the Overall PI within the timeframes detailed in the table below.  
 
 
 
 
Attribution 
DF/HCC Reportable AEs 
Gr. 2 & 3 AE 
Expected 
Gr. 2 & 3 AE 
Unexpected 
Gr. 4 AE Expected 
Gr. 4 AE 
Unexpected 
Gr. 5 AE 
Expected or 
Unexpected 
Unrelated 
Unlikely 
Not required 
Not required 
5 calendar days# 
5 calendar days 
24 hours* 
Possible 
Probable 
Definite 
 
Not required 
 
5 calendar days 
 
5 calendar days# 
 
5 calendar days 
 
24 hours* 
# If listed in protocol as expected and not requiring expedited reporting, event does not need to be reported. 
 
* For participants enrolled and actively participating in the study or for AEs occurring within 30 days of the last 
intervention, the AE should be reported within 24 business hours of learning of the event. 
 
 
The Overall PI will submit SAE reports from outside institutions to the DFCI OHRS according to DFCI 
IRB policies and procedures in reporting adverse events.  
 
7.3.4 
Protocol-Specific Expedited Adverse Event Reporting Exclusions 
N/A 
 
7.4 
Expedited Reporting to the Food and Drug Administration (FDA) 
 
The Overall PI, as study sponsor, will be responsible for all communications with the FDA. The Overall PI 
will report to the FDA, regardless of the site of occurrence, any serious adverse event that meets the FDA’s 
criteria for expedited reporting following the reporting requirements and timelines set by the FDA. 
 
7.5 
Expedited Reporting to Hospital Risk Management 
 
Participating investigators will report to their local Risk Management office any participant safety reports or 
sentinel events that require reporting according to institutional policy.  
 
7.6 
Routine Adverse Event Reporting 
 
All Adverse Events must be reported in routine study data submissions to the Overall PI on the toxicity case 
report forms.  AEs reported through expedited processes (e.g., reported to the IRB, FDA, etc.) must 
also be reported in routine study data submissions. 
 
7.7Adverse Event Reporting to Sponsor 
 
A summary report of adverse events that the DCC will prepare for the DSMB report will be sent to 
Transition Therapeutics. 
 


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8. PHARMACEUTICALINFORMATION 
 
A list of the adverse events and potential risks associated with the investigational agent administered in this 
study can be found in Section 7.1. 
 
8.1 
LY SARM 
 
8.1.1 
Description 
 
LY2452473 is a white to practically white solid. The chemical name is: carbamic acid, N-[(2S)-7-cyano-
1,2,3,4-tetrahydro-4-(2-pyridinylmethyl)cyclopent[b]indol-2-yl]-,1-methylester. The alternate chemical 
name is: (S)-(7-cyano-4-pyridin-2-ylmethyl-1,2,3,4-tetrahydro-cyclopenta[b]-carbamic acid isopropyl 
ester. The molecular formula is C22H22N4O2 and the molecular weight is 374.45 gmol-1. LY2452473 is 
practically insoluble in water, has a pKa of 3.17, pH of 9.2 and is stable when stored at room temperature. 
The chemical structure of LY2452473 is presented below: 
 
 
The plasma concentration-time profiles for LY2452473 after single dose up to 1000 mg showed 
measurable concentrations from 1 hour postdose, with maximum observed drug concentrations Cmax 4 to 
5 hours following dosing. The LY2452473 concentrations appeared to decline in a biexponential fashion 
characterized by a short distribution phase and a long terminal phase, with median terminal half-lives (t1/2) 
ranging between 26.6 and 55.1 hours across doses. Mean apparent oral clearance was low to moderate, 
ranging from 10.9 to 41.5 L/h across dose levels. The mean apparent volume of distribution at steady state 
(Vss/F) ranged from 388 to 2290 L across doses. Multiple dosing at 1 mg and 5 mg of LY2452473, also 
showed decline in a biexponential fashion characterized by a short distribution phase and a long terminal 
phase, with median terminal t½ ranging between 23.3 and 44.4 hours across doses The variability of Cmax 
at steady state (Cmax,ss) ranged from 14% to 84% across dose levels. The variability of AUC over the 
dosing interval at steady state (AUC[τ,ss]) ranged from 9% to 70% across dose levels. The pharmacokinetic 
characteristics observed supported once daily (QD) dosing. 
8.1.2 
Form 
LY2452473 is supplied for clinical use as an oral capsule drug product in size 2 opaque white gelatin 
capsules. Each capsule contains 1 mg, 5 mg or 15 mg of LY2452473 and the inactive ingredients 
pregelatinized starch and dimethicone. LY2452473 is intended to be supplied for the proposed clinical 
trial as capsules packaged in 30 count white, induction sealed high density polyethylene (HDPE) bottles 
with child-resistant closures. 
Our contractual agreement is with Transition Therapeutics.  The drug product will be packaged and 


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distributed by Catalent Pharma Solutions, Kansas City, Missouri, USA. 
8.1.3 
Storage and Stability 
 
The drug product will be stored at room temperature (25°C) with allowable excursions between 15 - 
30°C. The drug product, previously packaged in blister packages (2 mil Aclar, 10 count), was shown to 
be stable for 2 years under long-term storage conditions and for 6 months under accelerated storage 
conditions. Stability of the drug product in the current packaging configuration (HDPE bottle with child 
resistant closure) will be monitored under both long-term and accelerated conditions to ensure that the 
product meets stability specifications over the duration of the proposed clinical trial.     
8.1.4 
Compatibility 
 
Not applicable, as no adjunctive therapies will be used. 
 
8.1.5 
Handling 
 
Qualified personnel, familiar with procedures that minimize undue exposure to themselves and the 
environment, should undertake the preparation, handling, and safe disposal of the chemotherapeutic 
agent in a self-contained and protective environment.  
 
Since the drug product is supplied as an oral capsule, no special precautions or safety equipment are 
required for dispensing of the drug. The drug product must be stored at room temperature (25°C). 
 
8.1.6 
Availability 
 
Collaborative Agreement – Not available 
 
The drug product will be packaged and distributed by Catalent Pharma Solutions, Kansas City, 
Missouri, USA. 
 
8.1.7 
Preparation 
 
Not Applicable. The drug will be supplied as an oral capsule (size 2 opaque white gelatin) packaged in 
30 count white, induction sealed high density polyethylene (HDPE) bottles with child-resistant closures.  
 
8.1.8 
Administration 
 
The study medication will be taken orally, daily for 12-weeks. 
 
8.1.9 
Ordering 
 
The investigational drug will be ordered through Transition Therapeutics via the Data Coordinating 
Center.  The drug product will then be shipped directly to each site’s pharmacy.   
 
8.1.10 Accountability 
 
The investigator, or a responsible party designated by the investigator, should maintain a careful record 
of the inventory and disposition of the agent using the NCI Drug Accountability Record Form (DARF) 
or another comparable drug accountability form.  (See the NCI Investigator’s Handbook for Procedures 


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23 
 
for Drug Accountability and Storage.) 
 
The site study staff, designated by the investigator, will maintain a record of the inventory and 
disposition of the drug using the drug accountability form. The BWH Investigational Drug Services will 
also maintain a record of the study medication received from the manufacturer, the amount of study drug 
dispensed, and the amount returned or destroyed. 
 
8.1.11 Destruction and Return 
 
The unused supplies of the study drug will be returned by the study staff to BWH Investigational Drug 
Services, recorded, and destroyed by the BWH IDS. 
 
8.2 
Placebo 
 
The capsules containing the placebo and the LY SARM will be identical and they will be packaged in 
identical bottles and the label will not indicate whether the bottle contains active medication or placebo. 
Each capsule contains inactive ingredients pregelatinized starch and dimethicone similar in amount to that in 
active drug-containing capsules.  
 
The manufacturer will provide bulk supplies of placebo and active LY SARM 1 mg, 5 mg and 15 mg 
capsules. Although the placebo and LY SARM capsules will be identical in appearance and will have 
identical packaging, the pharmacy will have information on which bottles contain placebo and which 
contain active drug.  The BWH Investigational Drug Service utilizes the Investigational Drug Service 
Informatics System (IDSIS) to dispense placebo and investigational products in numerous clinical trials. 
The Investigational Drug Service Informatics System (IDSIS) employs bar scanning technology to verify 
the investigational medications dispensed against the subject’s treatment assignment in the clinical trials. 
 


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24 
9. STUDY CALENDAR 
Table 3. Schedule of Events 
 
Pre-screening 
Screening 
Baseline 
Intervention Period 
Off Treatment 
Day or Week 
 
Day -42 to 
Randomization 
Week 
2 
Week 
4 
Week 
6 
Week 
8 
Week 
12 
30 Days Post 
Last Dose 
Visit Number 
 
1 
2A 
2B 
 3 
 4 
 5 
 6 
7A 
7B 
 
Study Procedure 
 
 
 
 
 
 
 
 
 
Phone Prescreening 
X 
 
 
 
 
 
 
 
 
Informed Consent 
 
X 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
Review of Eligibility Criteria 
 
X 
 
 
 
 
 
 
 
Medical History 
 
X 
 
 
 
 
 
 
 
Concomitant Medications 
 
X 
 
 
 
 
 
 
 
Short Physical Performance Battery (SPPB) 
 
X 
 
 
 
 
 
 
 
Average Weekly Alcohol Consumption 
X 
X 
X 
X 
X 
X 
X 
X 
 
Questionnaires 
 
X 
X 
 
 
X 
 
X 
 
- 
FACIT-F, DISF 
 
X 
 
 
 
X 
 
X 
 
- 
Harbor-UCLA 7-Day Diary, EPIC, MSHQ, PANAS, SF-36, IPSS, IIEF, 
HED, SAID 
 
 
X 
 
 
X 
 
X 
 
Vital Signs 
 
X 
X 
 
 
X 
 
X 
 
Blood Draw* 
 
X 
X 
X 
X 
X 
 
X 
 
- 
HbA1c 
 
X 
 
 
 
 
 
 
 
- 
CBC, CMP with eGFR§, lipid panel 
 
X 
X 
 
 
X 
 
X 
 
- 
PSA 
 
X 
 
X 
X 
X 
 
X 
 
- 
Total testosterone, calculated free testosterone, SHBG 
 
X 
X 
 
 
X 
 
X 
 
- 
DHT, LH, estradiol 
 
 
X 
 
 
X 
 
X 
 
Physical Exam 
 
X 
 
 
 
X 
 
X 
 
EKG 
 
X 
 
 
 
 
 
 
 
Whole Body DXA 
 
 
X 
 
 
 
 
X 
 
Muscle Performance, Physical Function, and Aerobic Capacity Tests** 
 
 
X 
 
 
 
 
X 
 
Randomization 
 
 
X 
 
 
 
 
 
 
Drug Dispensing
 
 
X 
 
X 
 
X 
 
 
Adverse Events Monitoring 
 
 
X 
X 
X 
X 
X 
X 
X 
Interim Status 
 
 
X 
X 
X 
X 
X 
X 
X 
Medication Compliance Check 
 
 
 
 
X 
 
X 
X 
 
Planned Follow-Up Phone Call 
 
 
 
 
 
 
 
 
X 
Additional Blood Draw for Substudy*** 
- 
Bone markers (osteocalcin, C-telopeptide, P1NP, bone specific 
alkaline phosphatase), Apolipoproteins (A1 and B, lipoprotein 
particles),  Inflammatory markers (CRP, IL-6, C1 esterase inhibitor), 
HDL efflux, (TC) Insulin, (TC) HbA1c
 
 
X 
 
 
X 
 
X 
 
Note: Intervention visits window is +/- 3 days. Screening procedures may take place over the course of two visits if necessary.  
Baseline and Week 12 procedures will take place over the course of two visits. 
*All blood draws are fasting and will be completed at or before 11:00. 
**Aerobic capacity testing and muscle strength and physical function testing will take place on separate days. 


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25 
***Optional substudy participants only 
§ eGFR will be calculated retrospectively. 


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26 
 
10. MEASUREMENT OF EFFECT 
10.1 
Primary Outcome 
Our primary outcome is change in sexual activity score, assessed by the Harbor-UCLA 7-day Sexual Function 
Questionnaire, because sexual dysfunction is one of the most prevalent symptoms in men, who have undergone 
radical prostatectomy, and it affects HRQOL. This scale has been used widely in testosterone trials, and sexual 
activity scores, assessed by this instrument, are responsive to therapy. The scale covers 3domains: 1) sexual desire 
and enjoyment;2) sexual activity; and 3) mood.  
 
10.2 
Secondary outcomes 
Other measures of sexual function. Erectile function will be assessed by IIEF, SAID, and DISF-M-II.  
The IIEF which has been validated in many trials of ED therapies, and shown to be responsive to androgen therapy 
in men with ED and low testosterone. The IIEF is a 15-item questionnaire that evaluates 5 response domains, 
including erectile function, intercourse satisfaction, and overall satisfaction. It has been shown to have high degree 
of specificity and sensitivity, reliability, internal consistency, and construct validity.  
The DISF-M-IIis a 25-item questionnaire that provides an estimate of perceived quality of sexual activities in 5 
response domains: sexual desire/drive, sexual arousal, sexual activity, orgasm, and sexual satisfaction/partner 
relationship. It comprehensively evaluates sexual desire and has been shown to have androgen-treatment sensitivity. 
The DISF-M was the main sexual function questionnaire in the NIA-funded The Testosterone Trial which is a trial of 
800 men evaluating the role of androgens on sexual function.  
The SAID is an 8-item questionnaire that evaluates 3 response domains, including sexual thinking, sexual arousal, 
and sexual activity. This questionnaire was validated using separate qualitative studies and provides an assessment 
of items associated with hypogonadism291, 292. 
Sexual desire will be assessed by Men’s Sexual Health Questionnaire (MSHQ) and by libido-related questions in 
IIEF, SAID, and DISF-M-II. MSHQ, a25-item questionnaire, provides a more robust assessment of libido than IIEF, 
especially in men with urogenital symptoms240, has high degree of internal consistency, reliability, and ability to 
discriminate between men with and without lower urinary tract symptoms (LUTS) and sexual dysfunction.  
We will measure the impact of androgen deficiency and sexual dysfunction on HRQOL using the hormonal and 
sexual domains of the Expanded Prostate Cancer Index Composite (EPIC). The EPIC is a 50-item, disease-
specific HRQOL questionnaire designed to evaluate the impact of treatments on HRQOL in men with prostate 
cancer. Of its four domains, we will utilize the sexual and hormonal domains, which are affected by androgen 
deficiency and expected to improve with SARM therapy, and which are important to men with prostate cancer but 
are not weighed appropriately in generic HRQOL instruments. This instrument has been used in numerous prostate 
cancer trials, and shown to have high Cronbach alpha coefficient, construct validity, and excellent sensitivity to 
change in response to hormonal treatment.  
Fatigue will be assessed by the 13-item Functional Assessment of Chronic Illness Therapy fatigue scale(FACIT-F) 
and by the 4-item Hypogonadism Energy Diary (HED).  
The FACIT-F has been well-validated and responsive to treatment. SF-36 Vitality scale has also been used to assess 
vitality, but the FACIT-F is more sensitive to change in those with low vitality/high fatigue than SF36. Another 
reason for selecting FACIT-F is its inclusion as “legacy instrument” for the NIH Roadmap PROMIS Fatigue item 
bank. This will ensure comparability to PROMIS.  
The HED has been validated using separate qualitative studies and provides an assessment of low energy related to 
hypogonadism291, 292. 
Mood and well-being will be assessed by PANAS affectivity balance scale, which includes 10 questions each for 
Positive Affect and Negative Affect. Many behavioral scientists consider affectivity balance as the cleanest window 
on an individual’s wellbeing. The affectivity balance incorporates negative affects (e.g., anxiety, depression) as well 


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Protocol Version Date: 09/12/2018 
 
27 
as positive affects (e.g., joy).Testosterone has been reported to improve mood and affect in hypogonadal men. 
Alphas for negative and positive affect scales are 0.85 and 0.88, respectively; one-week test-retest reliabilities are 
0.81 and 0.79. The instrument can detect changes in well being related to chronic illnesses and cancer. 
Muscle Performance and Physical Function. We will assess physical function by measuring walking speed in the 
6-min walk, stair climbing power, and load carrying time, self-reported physical function by the PF10 (physical 
function domain of MOS SF-36), maximal voluntary strength in the leg press exercise by the 1-RM method, and 
skeletal muscle mass by dual energy X-ray absorptiometry (DXA). We have used these measures in many previous 
trials and they have been shown to be androgen-responsive.  
Hormone Levels. Total testosterone, DHT and estradiol will be measured by LC-MS/MS, free testosterone by 
equilibrium dialysis, and LH by an IFMA. These methods have been used in PI’s lab for >25 yrs.  
Safety measures: We will measure PSA, complete blood counts, plasma lipids, AST, ALT, bilirubin and alkaline 
phosphatase levels for safety monitoring.  A structured evaluation of cardiovascular adverse events will be 
performed using a form, developed for NIA-funded T trials. 
Physiologic measures. We will measure lean body mass using dual energy X-ray absorptiometry (DXA), and 
maximal voluntary strength as mediators of improvements in physical function. VO2max and to a lesser extent VO2 
peak are markers of a person’s aerobic capacity. The lactate threshold is a marker of one’s capacity for prolonged, 
submaximal work without lactate accumulation and fatigue. We recognize that relationships of these physiologic 
mechanisms for aerobic energy production to fatigue are complex because in addition to these physiologic 
mechanisms, psychological factors, such as depressive symptoms, mood and wellbeing affect an individual’s 
perception of fatigue; accordingly, we will also assess mood and depressive symptoms. We propose to split the 
assessments for muscle performance and physical function into two non-consecutive days of testing in order to 
reduce subject burden and ensure more accurate data. 
At baseline, we propose to perform the cardiopulmonary exercise test (CPXT) alone on the first day of baseline 
testing. It is a longer test requiring progressively increasing subject effort to volitional fatigue and requires about 60 
minutes to administer. It also provides valuable safety data that may be used prior to other physical function 
assessments. The remainder of the tests (the 6-minute walk test, the stair climb power tests, the 50-m walk tests, and 
the leg press strength test)will be administered on the second day of baseline testing with appropriate and 
standardized rest periods between tests.  
At baseline, we propose to perform the cardiopulmonary exercise test (CPXT) alone on the first day of testing. It is a 
longer test requiring progressively increasing subject effort to volitional fatigue and requires about 60 minutes to 
administer. It also provides valuable safety data that may be used prior to other physical function assessments. The 
remainder of the tests (the 6-minute walk test, the stair climb power tests, the 50-m walk tests, and the leg press 
strength test)will be administered on the second day of baseline testing with appropriate and standardized rest 
periods between tests.  
For the Week-12 (end of study) assessments, efforts will be made to repeat the test procedures in the same sequence 
and time of day; however, they could be altered to accommodate subject convenience and scheduling.  
 
11. DATA REPORTING / REGULATORY REQUIREMENTS 
 
Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 7.0 (Adverse Events: List 
and Reporting Requirements). 
 
11.1 
Data Reporting 
 
11.1.1 Method 
 
The ODQ will manage and coordinate quality checks on the data for this study. 


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28 
 
11.1.2 Responsibility for Data Submission 
 
All investigative sites are responsible for submitting data and/or data forms to the ODQ according to the 
schedule set by the ODQ. 
 
11.2 
Data Safety Monitoring 
 
In accordance with the National Institute of Nursing Research (NINR) requirements, an independent Data and 
Safety Monitoring Board will review and monitor study progress, toxicity, safety and other data from this study. The 
components of this committee and their safety review procedures are described in the NINR Data and Safety 
Monitoring Plan, located in Appendix B.” 
 
11.3 
Transmission of DSMB Recommendations and Summary Reports of Adverse Events to IRBs 
 
The transmission of DSMB Recommendations and Summary Reports of Adverse Events to IRBs for this trial is 
described in Appendix B.   
 
11.4 
Transmission of Summary of Closed Deliberations to the NINR Staff 
 
This is described in Appendix B.   
 
11.5 
Protecting the Confidentiality of Participant Data 
 
This is described in Appendix B.   
 
11.6 
Multicenter Guidelines 
 
This protocol will adhere to the policies and requirements of the DF/HCC Multi-Center Data and Safety Monitoring 
Plan.  The specific responsibilities of the Overall PI, Coordinating Center, and Participating Institutions and the 
procedures for auditing are presented in Appendix A. 
 
• The Overall PI/Coordinating Center is responsible for distributing all IND Action Letters or Safety Reports 
to all participating institutions for submission to their individual IRBs for action as required. 
 
• Mechanisms will be in place to ensure quality assurance, protocol compliance, and adverse event reporting at 
each site. 
 
• Except in very unusual circumstances, each participating institution will order the study agent(s) directly 
from supplier.  A participating site may order the agent(s) only after the initial IRB approval for the site has 
been forwarded to the Coordinating Center. 
 
11.7 
Collaborative Agreements Language 
N/A 
 
12. STATISTICAL CONSIDERATIONS 
 


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Protocol Version Date: 09/12/2018 
 
29 
STATISTICAL ANALYSIS 
 
12.1 
Descriptive Analyses 
 
Descriptive measures for each outcome and potential covariate will be computed. Graphical and tabular displays 
will be used to establish the distributional properties of outcomes and assess need for transformation. Preliminary 
assessments of association between covariates and outcomes will be obtained using semiparametric penalized 
likelihood approach implemented in generalized additive models256. We will use summary statistics and graphical 
techniques to compare baseline characteristics of groups.  
 
12.2 
Compliance Analysis 
 
Subject’s compliance will be assessed in terms of the number of doses used, based on pill counts, expressed as a 
percent of the total number of doses that should have been used.  
 
12.3 
Analytic plan 
 
Following appropriate variable transformations, the primary analysis will utilize mixed effects regression controlling 
for baseline values, randomization, and stratification. Primary inferential targets of interest will be difference in 
outcomes measures between the 4 arms, estimated using treatment contrasts. Secondary analyses will incorporate 
control for additional factors based on the results of exploratory analyses mentioned above. We will consider the 
possibility of potential bias due to three stages of enrollment by performing sensitivity analyses with stage effect 
adjustment293,294.Missing data will be accommodated using multiple imputation, with imputed values generated in 
accordance with the mixed effects model as implemented in the mice library in R257-259. Point estimates will be 
accompanied by 95% confidence intervals, and type-I error probability for hypothesis testing set at 0.05. Statistical 
analyses will be conducted using SAS version 9.3 or higher and R version 2.15.0.  
Specific Aim 1 is concerned with change in sexual function as measured by the Harbor-UCLA 7-day Sexual 
Function Questionnaire (SFQ) and other outcomes measured at baseline and during weeks 6 and 12. Six and 12 
week data will be analyzed simultaneously using mixed effects linear regression controlling for baseline measures as 
well as stratification factors (age and PDEI use), with site and subject treated as random effects. The primary 
analysis will be supplemented by comparisons of 12 week change in function, estimated via treatment contrast with 
statistical significance evaluated via likelihood ratio test. We will also compare the proportion of men achieving 
increase of >1 point on sexual function score (thought to approximate the minimal clinically important difference on 
the SFQ) using generalized estimating equations256 and modified Poisson regression approach257-259, which can 
accommodate repeated measurements and is preferable to odds ratio in prospective designs. If the rate of 
improvement is very low, a zero-inflated alternative will be considered210.  
 
Secondary Hypotheses. Specific Aim 2 is concerned with estimation of the effects of SARM administration on 
well-being, affectivity balance, fatigue and HRQOL. These will be obtained at randomization and at 6 and 12 
weeks. We will follow an analytic plan parallel to that described for Aim 1. Aim 3 is concerned with the effects of 
SARM on strength and physical function. As in Aims 1 and 2 we will utilize mixed effects regression. 
We will also consider further exploratory analyses of the primary endpoint. For example, we will use linear 
regression to determine whether changes in muscle strength and measures of physical function correlate with 
changes in muscle mass and whether improvements in aerobic capacity are associated with improved fatigue scores. 
Appropriate techniques will assess assumptions of linearity and homoscedasticity. 
 


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12.4 
Missing data 
 
All subjects who are randomized will be included in the analyses. We will use multiple imputation using chained 
equations (MICE) to accommodate missing data. Further, our analyses will use simple linear mixed models that use 
additional intermediate time points when available. These methods use available information more efficiently, thus 
reducing type II error. We recognize that missingness may be associated with outcome, in which case there exists 
the potential for biased estimates of treatment effect. Sensitivity analyses will be employed to assess this possibility.  
 
12.5 
Sample Size Estimates and Power Considerations 
 
Initially, we had estimated that 126 men will be needed to test the primary hypothesis based on assumptions of two 
sided type I error rate of 0.05, attrition rate of 20% and 90% power. Our primary outcome is change in sexual 
activity score derived from Harbor-UCLA Seven Day Sexual Function Questionnaire221. The primary targets of 
estimation was overall dose effect as well as the direct comparison of highest dose group (15 mg) to placebo, 
however due to stoppage of 15-mg dose group, the primary aim of this study will be comparison of 5-mg group to 
placebo. There are no randomized trial data on the effects of SARM on sexual function in men with prostate cancer. 
In several trials in hypogonadal men178, 183-184, testosterone therapy increased sexual activity score by an average of 
1.5 points. Here we assume that the difference of interest in the change in sexual activity score between the 15 mg 
dose and placebo over 3 months is 1.5 points with a standard deviation of 1.8 (1.27 within each group). We estimate 
that the difference between 1 mg and placebo is 0.3 points with SD 1.2 and, as previously assumed, between 5 mg 
and placebo is 1.2 with SD 1.8. Under these assumptions, group allocation of 36:28:36:14 (for placebo, 1mg, 5 mg 
and 15 mg groups, respectively) subjects per arm will achieve more than 95% power to reject the null hypothesis of 
no overall dose effect, and to detect the difference between the 15 mg group and placebo. As enrollment to 15-mg 
group has been stopped and insufficient number of participants were randomized to this group (N=14), there will not 
be any formal analysis testing difference between 15-mg arm to placebo. 
 
We will similarly obtain good power to detect clinically meaningful effects on other measures of sexual function. 
We hypothesize that the mean difference in change in sexual desire scores between the 15 mg and placebo groups is 
1.8 (SD 2.1). The proposed sample size has >95% power to detect this difference. Similarly, we will obtain >95% 
power to detect between group differences of 4 points in change in erectile function domain (EFD) of International 
Index of Erectile Dysfunction (IIEF) (assumed SD 6 points), a threshold deemed clinically significant222-225. The 
average increase in EFD score in trials of PDE5 inhibitors is 7153, 226-228. 
 
Assuming mean (SD) LBM changes of 0 (1) kg in placebo, 0.8 (1.2) at 1 mg, 1.5 (2.1) kg at 5 mg and 1.8 (2.1) kg at 
15 mg dose, simulation results indicate that this design achieves more than 90% power to demonstrate an overall 
dose-response relationship and to detect the advantage of 15 mg dose over placebo, where both tests are performed 
at the 0.05 level. Using the Holm-Bonferroni correction for these two non-independent hypotheses (both hypotheses 
must be rejected at the 0.05 level, and at least one at the 0.025 level, preserving the overall type-I error rate of 0.05), 
results indicate that the design achieves more than 80% power to reject both nulls simultaneously. Recent SARM 
trials have reported average gains of ~1.5 kg in lean body mass45, 48,116. In a testosterone trial in HIV-infected men, a 
difference of 2.9 kg in fat-free mass was observed between testosterone and placebo groups173. Testosterone trials in 
older men that used smaller doses of testosterone observed an increase of ~1.5 kg186.  
 
We anticipate that the change in leg press strength at 15 mg dose will be 15 kg (SD 18), at 5 mg dose 12 kg (SD 18 
kg) and at the 1 mg dose 4 kg (SD 6 kg), while placebo group is assumed to have no increase (SD 6). This 
assumption is based on testosterone trials in older men175,195, HIV-infected men173, and in men with COPD185. A 15 


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31 
 kg increase in leg press strength is deemed clinically significant because a 10 kg increase in leg strength was 
associated with improvements in walking speed232. Under these assumptions, simulation results demonstrate that the 
planned randomization will provide >90% power to jointly detect an overall dose-response pattern and a significant 
difference between the5 mg and placebo groups. In a SARM trial48, the increase in stair climbing power in men 
receiving enobosarm averaged 15% (SD 20%). The proposed sample size provides >80% power to detect a similar 
difference between 5 mg and placebo arms. For physical function domain of MOS-SF36, the difference of interest 
between 5 mg and placebo group is 4 points (SD 7 points), which is a moderate effect.  
 
In randomized trials in older men with low testosterone, the difference in change in physical function domain score 
between testosterone and placebo groups was 4 points186. Ware et al233 have determined that a 4-point change in the 
physical function domain of the MOS SF36 score is clinically meaningful. A proposed sample size provides >80% 
power to detect this effect size between placebo and 5 mg dose group.   
 
Absent intervention, the clinical PSA recurrence rate in this group of men should be <1% over 10 years54-57, so that 
few, if any clinical recurrences, are expected in the placebo arm over the three-month trial duration. We likewise 
anticipate few if any recurrences among subjects randomized to SARM. To insure that analyses are sensitive to even 
limited evidence of safety concerns, we will conduct a one-sided comparison of the proportion of subjects 
experiencing events in each arm using a Fisher’s exact test with type-I error probability set at 0.20, as recommended 
by some FDA panels. Assuming recurrence risk on placebo is 1%, this comparison will have 85% power to detect 
an increased risk of 10% in the 15 mg group.  
 
To accommodate attrition of up to 20%, we will enroll 37:25:37:36 men (for placebo, 1 mg, 5 mg and 15 mg groups, 
respectively) for a total of 135 men. Assumption of 20% attrition rate is conservative; the attrition in our 
testosterone trial in older men was 12%174. Even in a 3-year intervention trial to determine the effects of testosterone 
on atherosclerosis, the loss-to-follow-up has been <20%. The incorporation of 6-week measurement in the mixed 
effects model and the inclusion of all 114 subjects made possible by use of multiple imputation will provide even 
higher power than that claimed here.  
 
12.6 
DATA MANAGEMENT 
 
The Data Management Center (DMC) will provide data management and statistical programming under the 
supervision of Dr. Travison. A randomization application will be available online. Upon completion of Eligibility 
Form, a subject ID will be generated, and the randomization table will be queried for study arm designation. 
Database will track subjects, provide documentation of eligibility and consent, and provide alerts to study staff 
about due dates. The database will reside on a secure, password protected server, and backed up on a nightly basis. 
The DMC will prepare standardized data collection forms to ensure that all data fields are unambiguous, items are 
easily read, response categories are in standardized units, and the instructions are clearly worded. Validation rules 
including built-in edits such as range and logic checks will be incorporated into the verification process. After forms 
have been verified, programming codes will check across-form internal inconsistencies. The statistical programmer 
will be responsible for cleaning the data, creating analytic data sets, standardized protocols for coding data, and a 
data dictionary of variables, and for writing the analysis code for all analyses. 
 
The target sample size is 114 participants study-wide.  In order to randomize 114 subjects, we estimate that we will 
need 450 subjects to enroll (sign consent).  The study intervention includes placebo and three doses of LY SARM ( 
1, 5 and 15 mg daily).  It is planned for the recruitment to be split among the Brigham and Womens Hospital 
(BWH), the University of Florida (UFL), and Johns Hopkins Medical Institutes (JHMI). Ultimately, it is planned to 
have 68 subjects randomized at BWH, 27 subjects randomized at UFL, and 40 subjects randomized at Johns 


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32 
Hopkins Medical Institute.  A target sample size of 114 participants from two trial sites will have >90% power to 
test the primary hypothesis. 
 
Randomization: After protocol amendment, last 10 subjects who meet the eligibility criteria will be randomized to 
either the placebo or 5mg SARM daily.  Due to inclusion of new treatment arm (15 mg) in the study and stopping 
enrollment into the 1 mg group, and later stopping enrollment into the 15-mg group, participants will have been 
randomized in three stages. In the first stage, then=80 subjects were randomized to one of 3 groups: placebo, 1 mg 
and 5 mg, with allocation ratio of 1:1:1; this randomization scheme was ended after the amendment was approved. 
In the second stage, (according to protocol amendment, after stopping the enrolment in 1 mg group and inclusion of 
new 15 mg LYSARM dose group) N=24 participants were randomized with allocation ratio of 1:1:3 to placebo, 5 
mg and 15 mg groups, respectively. In the third stage, after stopping the enrollment in 15-mg group, due to safety 
signal, we anticipate to randomize 10 more participants with allocation ratio 3:2 (6 in placebo and and 4 in 5-mg 
dose). At the end of the trial we expect to enroll 114 participants (80 in the first stage, 24 in the second stage and 10 
in the third stage) with group allocation of 36:28:36:14 participants, for placebo, 1 mg, 5 mg and 15 mg groups, 
respectively.. The subject assignment will be based on the randomization tables, using permuted blocks with varying 
blocks sizes. Subjects will be stratified by age (19-50 and >50) and use of phosphodiesterase 5 inhibitors (PDEIs); 
PDEIs may influence sexual function (and mood and HRQOL) independently228-231. Stratification variables will be 
included as covariates in analyses. 
 
12.7 
Sample Size, Accrual Rate and Study Duration 
 
The revised planned sample size is114.  Enrollment is targeted to be completed in 3years from start of study 
initiation.  We anticipate that enrollment will average 45 subjects per year over the three years.  If enrollment is 
slower at the start, efforts will be enhanced to meet the 3 year enrollment goal.  There is a 12-week intervention 
period after the screening and baseline measures are obtained.  Section 9 of this document contains the Schedule of 
Events. Women are not eligible for this trial as this is a study of men with prostate cancer. 
 
 
 
Accrual Targets 
Ethnic Category 
Sex/Gender 
Females 
 
Males 
 
Total 
Hispanic or Latino 
0 
+ 
17 
= 
17 
Not Hispanic or Latino 
0 
+ 
118 
= 
118 
Ethnic Category: Total of all subjects 
0 
(A1) + 
135 
(B1) = 
135 
(C1) 
Racial Category 
 
American Indian or Alaskan Native 
0 
+ 
1 
= 
1 
Asian 
0 
+ 
1 
= 
1 
Black or African American 
0 
+ 
13 
= 
13 
Native Hawaiian or other Pacific 
Islander 
0 
+ 
0 
= 
0 
White 
0 
+ 
120 
= 
120 
Racial Category: Total of all subjects 
0 
(A2) + 
135 
(B2) = 
135 
(C2) 
 
(A1 = A2) 
 
(B1 = B2) 
 
(C1 = C2) 
 


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33 
12.8 
Stratification Factors 
 
There is no stratification in this study design. 
 
12.9 
Interim Monitoring Plan 
 
Please refer to the Data Safety Monitoring Plan in Section 11. 
 
12.10 Analysis of Primary Endpoints 
 
Please reference the analysis section 12 of this document. 
 
12.11 Analysis of Secondary Endpoints 
 
Please reference the analysis section 12 of this document. 
 
12.12 Reporting and Exclusions 
 
12.13 Evaluation of Toxicity 
Please reference Section 5.5 of this document. 
 
12.14 Evaluation of the Primary Efficacy Endpoint 
 
Please reference Section 12 of this document. 
 
13. 
PUBLICATION PLAN 
 
 
The results will be made public within 24 months of reaching the end of the study. The end of the study is the time 
point at which the last data items are to be reported, or after the outcome data are sufficiently mature for analysis.  
 
 


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34 
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APPENDIX A 
 
Dana-Farber/Harvard Cancer Center 
Multi-Center Data and Safety Monitoring Plan 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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APPENDIX A-TABLE OF CONTENTS 
1. 
OBJECTIVES ...................................................................................................................... 5 
1.1 
Study Design ....................................................................................................................... 5 
1.2 
Primary Objectives .............................................................................................................. 5 
1.3 
Secondary Objectives .......................................................................................................... 5 
2. 
BACKGROUND ................................................................................................................. 6 
2.1 
Study Disease(s) .................................................................................................................. 6 
2.2 
IND Agent ........................................................................................................................... 6 
2.3 
Rationale ............................................................................................................................. 7 
2.4 
Correlative Studies Background .......................................................................................... 8 
3. 
PARTICIPANT SELECTION ............................................................................................ 8 
3.1 
Eligibility Criteria ............................................................................................................... 9 
3.2 
Exclusion Criteria ................................................................................................................ 9 
3.3 
Screening, Recruitment, and Enrollment .......................................................................... 10 
4. 
REGISTRATION PROCEDURES ................................................................................... 11 
4.1 
General Guidelines for DF/HCC and DF/PCC Institutions .............................................. 11 
4.2 
Registration Process for DF/HCC and DF/PCC Institutions ............................................. 11 
4.3 
General Guidelines for Other Investigative Sites .............................................................. 12 
4.4 
Registration Process for Other Investigative Sites ............................................................ 12 
5. 
TREATMENT AND/OR IMAGING PLAN .................................................................... 12 
5.1 
Criteria and Process for Unblinding .................................................................................. 12 
5.2 
Treatment Regimen ........................................................................................................... 12 
5.3 
Pre-Treatment Criteria ....................................................................................................... 14 
5.4 
Agent Administration ........................................................................................................ 14 
5.5 
General Concomitant Medication and Supportive Care Guidelines ................................. 15 
5.6 
Criteria for Taking a Participant Off Protocol Therapy .................................................... 16 
5.7 
Duration of Follow Up ...................................................................................................... 17 
5.8 
Criteria for Taking a Participant Off Study ....................................................................... 17 
5.9 
Study Stopping Rules ........................................................................................................ 18 
6. 
DOSING DELAYS/DOSE MODIFICATIONS ............................................................... 18 
7. 
ADVERSE EVENTS:  LIST AND REPORTING REQUIREMENTS ............................ 18 
7.2 
Adverse Event Characteristics .......................................................................................... 19 
7.3 
Expedited Adverse Event Reporting ................................................................................. 19 
7.4 
Expedited Reporting to the Food and Drug Administration (FDA) .................................. 20 
7.5 
Expedited Reporting to Hospital Risk Management ......................................................... 20 
7.6 
Routine Adverse Event Reporting ..................................................................................... 20 
8. 
PHARMACEUTICAL INFORMATION ......................................................................... 21 
8.1 
LY SARM ......................................................................................................................... 21 
8.2 
Placebo .............................................................................................................................. 23 
9. 
STUDY CALENDAR ....................................................................................................... 24 
10. 
MEASUREMENT OF EFFECT ....................................................................................... 26 


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10.1 
Primary Outcome .............................................................................................................. 26 
10.2 
Secondary outcomes .......................................................................................................... 26 
11. 
DATA REPORTING / REGULATORY REQUIREMENTS ........................................... 27 
11.1 
Data Reporting .................................................................................................................. 27 
11.2 
Data Safety Monitoring ..................................................................................................... 28 
11.6 
Multicenter Guidelines ...................................................................................................... 28 
11.7 
Collaborative Agreements Language ................................................................................ 28 
12. 
STATISTICAL CONSIDERATIONS .............................................................................. 28 
12.7 
Sample Size, Accrual Rate and Study Duration ................................................................ 32 
12.8 
Stratification Factors ......................................................................................................... 33 
12.9 
Interim Monitoring Plan .................................................................................................... 33 
12.10 Analysis of Primary Endpoints ......................................................................................... 33 
12.11 Analysis of Secondary Endpoints ..................................................................................... 33 
12.12 Reporting and Exclusions .................................................................................................. 33 
13. 
PUBLICATION PLAN ..................................................................................................... 33 
REFERENCES .............................................................................................................................. 34 
284. 
Miller L, Hays RD 2000 Measures of adherence to antiretroviral drugs in clinical trials. HIV Clinical 
Trials 2000; 1:36-46. PMID: 11590488 ............................................................................ 52 
285. 
Davis LL, Broome ME, Cox RP. Maximizing retention in community-based clinical trials. Journal of 
Nursing Scholarship. 2002; 34:47-53 PMID: 11901967 ................................................... 52 
APPENDIX A................................................................................................................................ 53 
1. 
INTRODUCTION ............................................................................................................. 57 
1.1 
Purpose .............................................................................................................................. 57 
1.2 
Multi-Center Data and Safety Monitoring Plan Definitions ............................................. 57 
2. 
GENERAL ROLES AND RESPONSIBILITIES ............................................................. 57 
2.1 
DF/HCC Sponsor .............................................................................................................. 57 
2.2 
Coordinating Center .......................................................................................................... 58 
2.3 
Participating Institution ..................................................................................................... 58 
3. 
DF/HCC REQUIREMENTS FOR MULTI-CENTER PROTOCOLS ............................. 59 
3.1 
Protocol Distribution ......................................................................................................... 59 
3.2 
Protocol Revisions and Closures ....................................................................................... 59 
3.3 
Informed Consent Requirements ....................................................................................... 59 
3.4 
IRB Documentation........................................................................................................... 60 
3.5 
IRB Re-Approval .............................................................................................................. 60 
3.6 
Participant Confidentiality and Authorization Statement.................................................. 60 
3.7 
DF/HCC Multi-Center Protocol Registration Policy ........................................................ 60 
3.8 
DF/HCC Protocol Case Number ....................................................................................... 61 
3.9 
Safety Assessments and Toxicity Monitoring ................................................................... 62 
3.10 
Data Management ............................................................................................................. 63 
4. 
REQUISITIONING INVESTIGATIONAL DRUG ......................................................... 63 
5. 
MONITORING: QUALITY CONTROL .......................................................................... 63 


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5.1 
Ongoing Monitoring of Protocol Compliance ................................................................... 63 
5.2 
Monitoring Reports ........................................................................................................... 63 
5.3 
Accrual Monitoring ........................................................................................................... 64 
6. 
AUDITING: QUALITY ASSURANCE ........................................................................... 64 
6.1 
Audit Plan: NCI Sponsored Trials .................................................................................... 64 
6.3 
Audit Notification ............................................................................................................. 64 
6.4 
Audit Reports .................................................................................................................... 64 
6.5 
Participating Institution Performance ................................................................................ 64 
7. 
ThisquestionnaireisdesignedtomeasureQualityofLifeissuesinpatientswithProstatecancer. 
Tohelpusgetthemostaccuratemeasurement,itisimportantthatyouanswerallquestionshonestlyandcomple
tely. .................................................................................................................................... 80 
8. 
Today'sDate(pleaseenterdatewhensurveycompleted):MonthDayYear ............................... 80 
1. 
duringthelast4 weeks? ........................................................................ 82 
 
 
 


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1. INTRODUCTION 
 
1.1 
Purpose 
 
To establish standards that will ensure that a Dana-Farber/Harvard Cancer Center Multi-Center protocol will 
comply with Federal Regulations, Health Insurance Portability and Accountability Act (HIPAA) requirements and 
applicable DF/HCC Standard Operating Procedures.         
 
1.2 
Multi-Center Data and Safety Monitoring Plan Definitions 
 
DF/HCC Multi-Center Protocol:  A research protocol in which one or more outside institutions are collaborating 
with Dana-Farber/Harvard Cancer Center where a DF/HCC investigator is the sponsor. DF/HCC includes Dana-
Farber/Partners Cancer Care (DF/PCC) Network Clinical Trial Affiliates.  
 
Lead Institution:  Brigham and Women’s Hospital (BWH))  
 
DF/HCC Sponsor:  Shalender Bhasin, MD 
 
Participating Institutions:  Johns Hopkins Medical Institute and the University of Florida 
 
Supporting Referral Site to BWH:  Beth Israel Deaconess Medical Center 
 
Coordinating Center: Brigham and Women’s Hospital 
 
DF/HCC Office of Data Quality: ODQ 
 
2. GENERAL ROLES AND RESPONSIBILITIES 
 
2.1 
DF/HCC Sponsor 
 
The DF/HCC Sponsor, Shalender Bhasin, MD accepts responsibility for all aspects of conducting a DF/HCC Multi-
Center protocol which includes but is not limited to:  
• Oversee the coordination, development, submission, and approval of the protocol as well as subsequent 
amendments.  
• Ensure that the investigators, study team members, and Participating Institutions are qualified and 
appropriately resourced to conduct the protocol.   
• Include the Multi-Center Data and Safety Monitoring Plan as an appendix to the protocol. 
• Ensure all Participating Institutions are using the correct version of the protocol. 
• Ensure that each participating investigator and study team member receives adequate protocol training 
and/or a Site Initiation Visit prior to enrolling participants and throughout trial’s conduct as needed. 
• Ensure the protocol will be provided to each participating site in a language understandable to all applicable 
site personnel when English is not the primary language.  
• Monitor progress and overall conduct of the study at all Participating Institutions.  
• Ensure all DFCI Institutional Review Board (IRB), DF/HCC, NINR, and FDA reporting requirements are 
met.  
• Review data and maintain timely submission of data for study analysis.  
• Act as the single liaison with FDA (investigator-held IND trials) 


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• Ensure compliance with all requirements as set forth in the Code of Federal Regulations, applicable 
DF/HCC requirements, HIPAA requirements, and the approved protocol. 
• Commit to the provision that the protocol will not be rewritten or modified by anyone other than the 
DF/HCC Sponsor. 
• Identify and qualify Participating Institutions and obtain accrual commitments prior to extending the 
protocol to that site. 
• Monitor accrual and address Participating Institutions that are not meeting their accrual requirements.  
 
2.2 
Coordinating Center 
 
The general responsibilities of the Coordinating Center may include but are not limited to: 
• Assist in protocol development.  
• Maintain FDA correspondence. 
• Review registration materials for eligibility and register participants from Participating Institutions with 
DF/HCCODQ. 
• Distribute protocol and informed consent document updates to Participating Institutions as needed. 
• Oversee the data collection process from Participating Institutions. 
• Maintain documentation of Serious Adverse Event (SAE) reports and deviations/violation submitted by 
Participating Institutions and provide to the DF/HCC Sponsor for timely review.   
• Distribute serious adverse events reported to the DF/HCC Sponsor that fall under the DFCI IRB Adverse 
Event Reporting Policy to all Participating Institutions. 
• Provide Participating Institutions with information regarding DF/HCC requirements that they will be 
expected to comply with. 
 
• Carry out plan to monitor Participating Institutions either by on-site or remote monitoring.  
Conduct regular communications with all Participating Institutions (conference calls, emails, etc) with 
relevant documentation maintained.  
 
2.3 
Participating Institution 
 
The Johns Hopkins Medical Institute and the University of Florida are expected to comply with all applicable 
federal regulations and DF/HCC requirements, the protocol and HIPAA requirements.  
 
The general responsibilities of the Participating Institution include but are not limited to: 
• Document the delegation of research specific activities to study personnel. 
• Commit to the accrual of participants to the protocol. 
• Submit protocol and/or amendments to their local IRB. 
• Maintain regulatory files as per sponsor requirements. 
• Provide the Coordinating Center with regulatory documents or source documents as requested. 
• Participate in protocol training prior to enrolling participants and throughout the trial as required (i.e. 
teleconferences). 
• Update Coordinating Center with research staff changes on a timely basis. 
• Register participants through the Coordinating Center prior to beginning research related activities.  
• Submit Serious Adverse Event (SAE) reports to local IRB per local requirements and to the Coordinating 
Center, in accordance with DF/HCC requirements.  
• Submit protocol deviations and violations to local IRB per local requirements and to the DF/HCC Sponsor 
in accordance with DF/HCC requirements. 


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• Order, store and dispense investigational agents and/or other protocol mandated drugs per federal guidelines 
and protocol requirements. 
• Have office space, office equipment, and internet access that meet HIPAA standards. 
• Participate in any quality assurance activities and meet with monitors or auditors at the conclusion of a visit 
to review findings. 
• Promptly provide follow-up and/or corrective action plans for any monitoring queries or audit findings. 
 
3. DF/HCC REQUIREMENTS FOR MULTI-CENTER PROTOCOLS 
 
 
3.1 
Protocol Distribution 
 
The Coordinating Center will distribute the final DFCI IRB approved protocol and any subsequent amended 
protocols to all Participating Institutions.    
 
3.2 
Protocol Revisions and Closures 
 
The Participating Institutions will receive notification of protocol revisions and closures from the Coordinating 
Center.  It is the individual Participating Institution’s responsibility to notify its IRB of these revisions. 
 
• Non life-threatening revisions: Participating Institutions will receive written notification of protocol 
revisions regarding non life-threatening events from the Coordinating Center. Non-life-threatening protocol 
revisions must be IRB approved and implemented within 90 days from receipt of the notification. 
 
• Revisions for life-threatening causes: Participating Institutions will receive immediate notification from 
the Coordinating Center concerning protocol revisions required to protect lives with follow-up by fax, mail, 
e-mail, etc.  Life-threatening protocol revisions will be implemented immediately followed by IRB request 
for approval. 
 
• Protocol closures and temporary holds: Participating Institutions will receive notification of protocol 
closures and temporary holds from the Coordinating Center. Closures and holds will be effective 
immediately.  In addition, the Coordinating Center, will update the Participating Institutions on an ongoing 
basis about protocol accrual data so that they will be aware of imminent protocol closures. 
 
3.3 
Informed Consent Requirements 
 
 
Participating Institutions will send their version of the informed consent document and HIPAA authorization, if a 
separate document, to the Coordinating Center for review and approval prior to submission to their local IRB. The 
approved consent form must also be submitted to the Coordinating Center after approval by the local IRB for all 
consent versions. 
 
The Principal Investigator (PI) at each Participating Institution will identify the physician members or responsible 
study members of the study team who will be obtaining consent and signing the consent form for therapeutic 
protocols.  Participating institutions must follow the DF/HCC requirement that only attending physicians obtain 
informed consent and re-consent to interventional trials (i.e. drug and/or device trials).   
 


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3.4 
IRB Documentation 
 
The following must be on file with the Coordinating Center: 
• Initial approval letter of the Participating Institution's IRB.  
• Copy of the Informed Consent Form(s) approved by the Participating Institution’s IRB.  
• Participating Institution’s IRB approval for all amendments. 
• Annual approval letters by the Participating Institution's IRB. 
 
 
3.5 
IRB Re-Approval 
 
Verification of IRB re-approval from the Participating Institutions is required in order to continue research 
activities.  There is no grace period for continuing approvals. 
 
The Coordinating Center will not register participants if a re-approval letter is not receive from the Participating 
Institution on or before the anniversary of the previous approval date.   
 
 
3.6 
Participant Confidentiality and Authorization Statement 
 
The Coordinating Center, with the approval from the DFCI IRB, will provide a consent template, with 
information regarding authorization for the disclosure of protected health information. Subject confidentiality will 
be maintained except as may be required by law. All identifying information will be kept in a secure area at all 
times. Consent form(s) will be maintained in a separate folder from original Case Report Forms at the conclusion 
of the study. Only de-identified data will be used for analyses. 
The DF/HCC Sponsor will use all efforts to limit its use of protected health information in its trials. However, 
because of the nature of these trials, certain protected health information must be collected. DF/HCC has chosen to 
use authorizations, signed by the participant in the trial, rather than limited data sets with data use agreements. 
 
3.6.1 
 DF/HCC Multi-Center Protocol Confidentiality 
 
All documents, investigative reports, or information relating to the participant are strictly confidential. Whenever 
reasonably feasible, any participant specific reports submitted to the Coordinating Center should be de-identified. 
It is recommended that the assigned DF/HCC ODQ case number be used for all participant specific documents. 
Participant initials may be included or retained for cross verification of identification.  
 
3.7 
DF/HCC Multi-Center Protocol Registration Policy 
 
3.7.1 
 Participant Registration and Randomization  
The following documents will be completed by the Participating Institution and e-mailed to the Coordinating 
Center, Maricelle Ramirez (mramirez5@partners.org) 
• Copy of required laboratory tests including: CBC, PSA, chemistry panel, TSH, total and free 
testosterone 
• Copy of the signed informed consent document (original to remain on site) 
• HIPAA authorization form (if separate from the informed consent document) 


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• Other appropriate forms: Eligibility Screening Worksheet, Registration form 
 
The Coordinating Center will review the submitted documents in order to verify eligibility and consent. To 
complete the registration process, the Coordinating Center will: 
• Register the participant on the study with the DF/HCC ODQ 
• Upon receiving confirmation of registration by the ODQ, the Coordinating Center will inform the 
Participating Institution and provide the study specific participant case number. The QACT will 
communicate the treatment assignment directly to the site’s research pharmacy.  
 
Treatment may not begin without confirmation from the Coordinating Center that the participant has been 
registered.  
 
• It should be noted that subjects referred through BIDMC to BWH will be registered via the BWH 
registration procedures. 
 
 
3.7.2 
 Initiation of Therapy 
 
Participants must be registered with the DF/HCC ODQ before receiving treatment.  Treatment may not be initiated 
until the Participating Institution receives confirmation of the participant’s registration from the Coordinating 
Center. The DF/HCC Sponsor and DFCI IRB must be notified of any violations to this policy. 
 
3.7.3 
 Eligibility Exceptions 
 
The DF/HCC ODQ will make no exceptions to the eligibility requirements for randomized trials.  
 
3.8 
DF/HCC Protocol Case Number 
 
At the time of registration, ODQ requires the following identifiers for all subjects: initials, date of birth, gender, 
race and ethnicity. Once eligibility has been established and the participant successfully registered, the participant 
is assigned a unique protocol case number.  Participating Institutions should submit all de-identified subsequent 
communication and documents to the Coordinating Center, using this case number to identify the subject.   
 
3.8.1 
Protocol Deviations, Exceptions and Violations 
 
The site investigators are not allowed to initiate changes in approved research without IRB review and approval, 
except when necessary to eliminate apparent immediate hazards to the participant. Any departure from the defined 
procedures set forth in the IRB approved protocol must be reported to the DF/HCC Sponsor, who in turn is 
responsible for reporting to the DFCI IRB. 
 
 
3.8.2 
 Definitions 
 
Protocol Deviation: Any departure from the defined procedures set forth in the IRB-approved protocol which is 
prospectively approved prior to its implementation. 
 
Protocol Exception:  Any protocol deviation that relates to the eligibility criteria, e.g. 
enrollment of a participant who does not meet all inclusion/exclusion criteria. 


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Protocol Violation: Any protocol deviation that was not prospectively approved by the IRB prior to its initiation or 
implementation.  
 
 
3.8.3 
 Reporting Procedures 
 
DF/HCC Sponsor, Shalender Bhasin, MD, is responsible for ensuring that clear documentation is available in the 
medical record and/or regulatory documents to describe all protocol exceptions, deviations and violations. The 
DF/HCC Sponsor will also be responsible for ensuring that all protocol violations/deviations are promptly reported 
per DFCI IRB guidelines.  
 
Participating Institutions: Protocol deviations require prospective approval from the DFCI IRB. The Participating 
Institution must submit the deviation request to the Coordinating Center who will then submit the deviation request 
to the DFCI IRB. Upon DFCI IRB approval the deviation is submitted to the Participating Institution IRB, per 
institutional policy. A copy of the Participating Institution’s IRB report and determination will be forwarded to the 
Coordinating Center within 10 business days after the original submission.  
 
All protocol violations must be sent to the Coordinating Center in a timely manner.  
 
Coordinating Center:  Upon receipt of the violation/deviation report from the Participating Institution, the 
Coordinating Center will submit the report to the DF/HCC Sponsor for review. Subsequently, the Participating 
Institution’s IRB violation/deviation report will be submitted to the DFCI IRB for review per DFCI IRB reporting 
guidelines. DF/HCC will forward all violation reports to CTEP via an internal DF/HCC process, as applicable. 
 
3.9 
Safety Assessments and Toxicity Monitoring 
 
The study teams at all participating institutions are responsible for protecting the safety, rights and well-being of 
study participants. Recording and reporting of adverse events that occur during the course of a study help ensure 
the continuing safety of study participants.  
 
All participants receiving investigational agents and/or other protocol mandated treatment will be evaluated for 
safety. The safety parameters include complete blood counts, blood chemistries, PSA, periodic physical 
examination findings, and spontaneous reports of adverse events reported by participants.  All toxicities 
encountered during the study will be evaluated according to the criteria specified in the protocol. Life-threatening 
toxicities must be reported immediately to the DF/HCC Sponsor via the Coordinating Center.  
 
3.9.1 
Guidelines for Reporting Serious Adverse Events  
 
Guidelines for reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) are detailed in the Data and 
Safety Monitoring Plan (appended to this document). 
 
 
 
 
Participating Institutions must report the SAEs to the DF/HCC Sponsor and the Coordinating Center following the 
DFCI IRB Adverse Event Reporting Policy.  
 
The Coordinating Center will maintain documentation of all Participating Institution Adverse Event reports and be 
responsible for communicating to all participating investigators, any observations reportable under the DFCI IRB 


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Reporting Requirements.  Participating Institutions will review and submit to their IRB according to their 
institutional policies and procedures 
 
3.9.2 
Guidelines for Processing IND Safety Reports  
 
The DF/HCC Sponsor will review all IND Safety Reports and ensure that all IND Safety Reports are distributed 
to the Participating Institutions. Participating Institutions will review and submit to their IRB according to their 
institutional policies and procedures. 
 
 
3.10 
Data Management 
 
The trial’s Data Coordinating Center in collaboration with the study team will develop case report forms (CRF), 
for use with the protocol.  These forms are designed to collect data for each study. Each institution is responsible 
for its own data quality and review. 
 
Data is required to be entered within 14 days of data collection. 
 
 
4. REQUISITIONING INVESTIGATIONAL DRUG 
 
The ordering of investigational agent is specified in the protocol section 8.0. 
 
5. MONITORING: QUALITY CONTROL 
 
The Coordinating Center, with the aid of the ODQ provides quality control oversight for the protocol. 
 
5.1 
Ongoing Monitoring of Protocol Compliance 
 
The Coordinating Center will implement ongoing monitoring activities to ensure that Participating Institutions are 
complying with regulatory and protocol requirements, data quality, and participant safety. Monitoring will occur 
during protocol performance and through study completion. Additional monitoring practices may include but are 
not limited to; source verification, review and analysis of the following: eligibility requirements of all participants, 
informed consent procedures, adverse events and all associated documentation, study drug administration/treatment, 
regulatory files, protocol departures, pharmacy records, response assessments, and data management.  
Monitoring will occur every 6 months during the first year and then annually.  Additional monitoring may occur at 
the discretion of the DF/HCC Sponsor if incidences of non-compliance are discovered. 
Participating institutions will be required to participate in monthly Coordinating Center initiated teleconferences.  
Source documentation verification (SDV) will be conducted by having access to participants’ complete study 
records and source documents. 
 
5.2 
Monitoring Reports 
 
The DF/HCC Sponsor, Shalender Bhasin, MD, will review all monitoring reports for on-site and remote monitoring 
of Participating Institutions to ensure protocol compliance. Participating Institutions may also be subject to an audit 
as determined by the DF/HCC Sponsor. 


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5.3 
Accrual Monitoring 
 
Prior to extending a protocol to an external site, the DF/HCC Sponsor will establish accrual requirements for each 
participating institution. Each site will accrue at least 3  subjects per year. Accrual will be monitored for each 
participating institution by the DF/HCC Sponsor or designee. Sites that are not meeting their accrual expectations 
may be subject to termination.  
 
6. AUDITING: QUALITY ASSURANCE 
 
6.1 
Audit Plan: NCI Sponsored Trials 
 
Not applicable 
 
6.2 Audit Plan: DF/HCC Sponsored Trials 
 
One on-site audit will be scheduled by the ODQ, assuming at least three participants have been treated on protocol 
at the site. Approximately 3-4 participants would be audited at the site over a 2 day period.  If violations which 
impact participant safety or the integrity of the study are found, more participant records may be audited.  
 
6.3 
Audit Notification 
 
It is the Participating Institution’s responsibility to notify the Coordinating Center of all scheduled audit dates 
(internal or NCI) and re-audit dates (if applicable), which involve this protocol. All institutions will forward a copy 
of final audit and/or re-audit reports and corrective action plans (if applicable) to the Coordinating Center, within 
12 weeks after the audit date.  
 
6.4 
Audit Reports 
 
The DF/HCC Sponsor, Shalender Bhasin, MD, will review all final audit reports and corrective action plans if 
applicable. The Coordinating Center, will forward these reports to the DF/HCC ODQ per DF/HCC policy for 
review by the DF/HCC Audit Committee. Based upon the audit assessments the DF/HCC Audit Committee could 
accept or conditionally accept the audit rating and final report. Conditional approval could require the DF/HCC 
Sponsor to implement recommendations or require further follow-up.  For unacceptable audits, the DF/HCC Audit 
Committee would forward the final audit report and corrective action plan to the DFCI IRB as applicable. 
 
6.5 
Participating Institution Performance 
 
The DF/HCC Sponsor is charged with considering the totality of an institution’s performance in considering 
institutional participation in the protocol. 
6.5.1 
Corrective Actions 
 
Participating Institutions that fail to meet the performance goals of accrual, submission of timely and accurate data, 
adherence to protocol requirements, and compliance with state and federal regulations, may be recommended for a six-
month probation period. Such institutions must respond with a corrective action plan and must demonstrate during the 
probation period that deficiencies have been corrected, as evidenced by the improved performance measures. Participating 
Institutions that fail to demonstrate significant improvement will be considered by the DF/HCC Sponsor for revocation 


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of participation. A DF/HCC Sponsor may terminate a site’s participation if it is determined that a site is not fulfilling its 
responsibilities as described above. 


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DFCI IRB Protocol #: 15-120 
 
 
 
 
 
APPENDIX B- NINR Data and Safety Monitoring Plan 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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DATA AND SAFETY MONITORING PLAN 
1RO1NR014502-01A1, PI: Bhasin, Shalender 
 
The Data and Safety Monitoring Plan (DSMP) for this trial, described below, will be reviewed and approved by 
the NINR staff prior to the commencement of any human subjects activities in this trial. The DSMP approved by 
the NINR staff will then be submitted to the local IRB for its review and approval. It is understood that the IRB 
approval of the NINR-approved DSMP is required before human subjects activities can take place within the trial, 
and that the awardee institution is responsible for approving the DSMB. 
The responsibility for compliance with the DSMP rests with the PI. The oversight of the monitoring activity 
described in the DSMP is the responsibility of the NINR staff. NINR will be notified within 7 days if the human 
subjects research or DSMP is changed prior to or during the implementation of the clinical trial. The NINR 
program staff must approve the changes prior to implementation.   
 
The essential components of the DSM Plan are the following: 
a. A Data and Safety Monitoring Board (DSMB), an independent committee charged with reviewing safety 
and trial progress and providing advice with respect to study continuation, modification, and termination, 
will assume oversight of the study, in accordance with NINR policy, once the study is underway. The 
procedures that will be used for data and safety monitoring are outlined below. 
b. The DSMB will include five individuals, including a chair and a separate executive secretary. All five 
members will be voting members. The DSMB members will have expertise in prostate cancer, androgen 
biology, biostatistical analysis of clinical trials data, and the conduct and oversight of clinical trials in 
prostate cancer patients.  These individuals will be approved by the institutional review board for human 
subjects research (IRB) after review of their expertise and potential conflicts of interest. The composition 
of the DSMB will consist of the following:  
• Two nationally or internationally recognized experts in prostate cancer and clinical trials of men with prostate 
cancer  
• An expert with nursing background and experience in symptom management including fatigue and other 
outcomes being assessed in this trial 
• An endocrinologist with expertise in clinical trials of androgens in men 
• A biostatistician with expertise in the design and analysis of clinical trials 
 
Safety Review Procedures: 
1.) 
The DSMB will meet to review the safety data every 6 months.   This review will take place by 
teleconference.  A majority must be present at the DSMB meeting to have a quorum.  
2.) 
Generation of safety reports. The Study’s PI, with the assistance of the Data Management Center 
(DMC) will prepare and submit the safety reports for DSMB review, This will be done in a blinded 
fashion, while protecting the confidentiality of participant data.  The reports will be given to an 
independent third party who will add a code (A, B, or C) to the data for each treatment group.  The 
third party will place the finished report into an envelope, seal the envelope and sign across the seal.  


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He/she will place this envelope containing the coded safety report into Fed Ex envelopes, pre-
prepared by the research coordinators, and seal those.  The reports will be sent, by Fed Ex, to the 
various DSMB members.  This will allow the DSMB to review the safety data by individual treatment 
groups.  The third party will store, in a locked cabinet, the code for the trial.  In the event that the 
DSMB requests unblinding of the study, the code will be sent from the third party directly to the 
DSMB. Thus, the DSMB members can have access to the categorized data, while the investigating 
team remains blinded.  
3.) 
Review of all adverse events will be performed by treatment group (coded A, B, or C). 
4.) 
Each safety report will include the enrollment status, including the number of subjects recruited, 
screened, and randomized.  In addition, it will incorporate the number of dropouts and the reason for 
the dropouts.  The investigating team will comply with NIH, FDA, and institutional policies on 
reporting adverse events.  The report will list all adverse events since the previous reporting period.  
In addition, a cumulative list of all adverse events will also be provided to the DSMB members. The 
summary of all adverse events will allow for a comprehensive overview or analysis of the events 
rates.  All AE’s will be evaluated for severity and attribution.  In order to protect participant 
confidentiality, the data provided to the DSMB will be coded so that individual patients cannot be 
identified. 
5.) 
Each DSMB meeting will be comprised of 2 portions.  Research personnel will arrange and be 
present for the “open discussions” at the start of the DSMB meetings.  The initial “open” portion of 
the meeting will have study personnel available to give a brief update on the status of the trial and to 
respond to any questions that the DSMB may have.  The second portion of the meetings will be 
“closed” to study personnel so that DSMB members may have independent deliberations.  Provisions 
will be made for study personnel to be available to the DSMB committee during these deliberations, 
should their input be required. 
6.) 
In addition to these review procedures the DSMB will receive copies of all serious adverse events, 
with study group assignment (A or B), as they occur. 
Transmission of DSMB Recommendations and Summary Reports of Adverse Events to IRBs  
A summary of the DSMB review and recommendations without treatment assignment information will be sent to 
the Principal Investigator after each DSMB meeting.  The PI will then forward the DSMB report, including the 
DSMB’s assessment of adverse events within the trial, to the IRBs of the participating institutions. 
Transmission of Summary of Closed Deliberations to the NINR Staff 
The NINR Program Officer will receive a copy of the “closed” deliberations. This information will be kept in a secure 
file, accessible only to the NINR Program Staff. 
Procedures for monitoring study safety: 
1. Monitoring schedule 
a. Adverse events are solicited and recorded by study staff at each study visit. 
b. PSA is measured at screening and weeks 2, 4, 6, and 12. 
c. Other safety labs – complete blood counts and chemistries – are measured at screening, baseline and 
during weeks 6 and 12. 
2. Auditing of selected cases for compliance with IRB requirements, conformance with informed consent 
requirements, verification of source documents, and investigator compliance will be performed by Brigham 
and Women’s Hospital’s institutional compliance officer annually. 


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3. Procedures for minimizing research-associated risk.  
All subjects will be monitored by frequent physical examinations, blood counts, chemistries and PSA levels. We 
will follow hematocrit, plasma lipids, blood chemistries, PSA and record all adverse events reported by the subjects 
every 4-weeks.  
The risks of blood drawing will be minimized by having only experienced practitioners perform phlebotomy.  
 
The risk of injury from participating in exercise testing will be minimized by several safety measures.  The 
subjects will be instructed in proper technique and the risks minimized by careful supervision.  Patients will be screened 
with cardiopulmonary exercise testing with continuous monitoring of the ECG to rule out cardiac ischemia and serious 
arrhythmias.  This test will be administered and supervised according to current American Heart Association 
guidelines1.  The likelihood of musculoskeletal injury from exercise testing will be minimized by providing a warm-up 
period preceding each exercise session including low speed treadmill walking and stretching exercises.  Further, a 
certified exercise physiologist will oversee all exercise testing sessions. 
 
The risks of SARM therapy will be minimized by close monitoring with serial physical examinations, 
hematocrit, and PSA levels. We have incorporated all the procedures recommended by the Expert Panel of the 
Endocrine Society on Androgen Deficiency Syndromes, ISSAM, and the American College of Physicians/American 
Society of Internal Medicine Disease Management Module for Male Hypogonadism for monitoring of men receiving an 
androgen. Although these guidelines were developed for testosterone therapy, they are appropriate for following men 
receiving any type of androgen therapy. We have incorporated in this trial several additional measures to minimize risk: 
a. The selection of LY SARM, which not only spares the prostate but has been shown in preclinical models to act 
as an androgen antagonist on the prostate, induce prostate atrophy in a canine model, inhibit the growth of 
prostate cancer explants in mice, and lower PSA in men.  
b. The inclusion and exclusion criteria will assure selection of subjects at very low risk of disease recurrence. 
c. We have established rigorously defined criteria for biochemical recurrence and for progression from stage 1. 
d. We have established a priori stopping rules based on PSA change. 
e. We will perform frequent PSA measurements to ensure early detection of biochemical recurrence. 
f. We will designate study clinicians to monitor PSA and other laboratory tests at each site. 
g. An independent DSMB will oversee the study after its initiation   
Protecting the confidentiality of participant data 
Subject confidentiality will be maintained except as may be required by law. All identifying information will be 
kept in a secure area at all times. Consent form(s) will be maintained in a separate folder from original Case Report 
Forms at the conclusion of the study. Only de-identified data will be used for analyses. 
Procedures for identifying, reviewing, and reporting of adverse events and unanticipated problems to the IRB, 
NINR, and FDA 
The adverse events will be identified by the study staff and reviewed by a study physician on an ongoing basis. Serious 
adverse events will be reported by the study PI to the DSMB Chair, FDA and NINR staff. Unanticipated problems will 
be reported to the DSMB, IRB, FDA, and NINR staff by the study’s PI. 
Termination Criteria 
The following Termination Criteria will be used: 


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• 
An increase in PSA to 0.2 ng/mL or higher, if confirmed by a repeated test, will result in treatment 
discontinuation and referral to a urologist. 
• 
Any evidence of disease recurrence will lead to immediate treatment discontinuation.  
• 
An increase in hematocrit above 54%, if confirmed by a repeated test, would warrant discontinuation of treatment. 
• 
Transaminase elevation above 3 times the upper limit of normal, if confirmed by a repeated test, would warrant 
discontinuation of treatment. 
• 
Myocardial infarction or stroke   
We recognize that other unexpected adverse events can occur. Therefore, we have instituted a comprehensive plan for 
early detection of adverse events; the Data Safety Monitoring Board will be empowered to discontinue treatment in one 
or more subjects, or halt the study, should the occurrence of adverse events so warrant. 
Procedures ensuring compliance with the monitoring plan and reporting requirements across sites 
As this is a three-site study, a study monitor will visit each of the three sites to monitor compliance with the study 
protocol, monitoring plan, and reporting requirements. These visits will take place every 6 months in the first year and 
then annually. 
 
An assessment of external factors or relevant information that may have an impact on safety of the participants 
or on the ethics of the study.  
The study team will provide this assessment to the DSMB (6-monthly) and IRB (annual) reports.  
 
Interim or Futility Analysis 
There are no plans for an interim or futility analysis. 
 
Additional Components of the DSM Plan 
The PI will provide reporting to the NINR staff of the following. All personal identifiers will be removed from any 
documents sent to NINR staff. 
1. Unanticipated problems or unexpected serious adverse events that may be related to the study protocol 
2. IRB-approved revisions to the study protocol that indicate a change in risks to the participants 
3. A summary of recommendations made by the DSMB and if applicable, an action plan for response 
4. Notice of any actions taken by the IRB or regulatory bodies regarding the research and any responses to those 
actions 
 
REFERENCES 
 
Myers J, Forman DE, Balady GJ, Franklin BA, Nelson-Worel J, Martin BJ, Herbert WG, Guazzi M, Arena R 2014, 
Sept 16. Supervision of exercise testing by nonphysicians: a scientific statement from the American Heart Association. 
American Heart Association Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention of the Council on 
Clinical Cardiology, Council on Lifestyle and Cardiometabolic Health, Council on Epidemiology and Prevention, and 
Council on Cardiovascular and Stroke Nursing. 130 (12): 1014-1027. PMID: 25223774 
 
 
 


NCI Protocol #:Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 09/12/2018 
 
71 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DFCI IRB Protocol #: 15-120 
 
APPENDIX C- Study Questionnaires 


NCI Protocol #:Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 09/12/2018 
 
72 
FACIT Fatigue Questionnaire 
 
Below is a list of statements that other people with your illness have said are important. Please circle or mark 
one number per line to indicate your response as it applies to the past 7 days. 
 
 
 
 
Not 
at all 
A little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
 
HI7 
I feel fatigued
 ..........................................................................................  
0 
1 
2 
3 
4 
HI12 
I feel weak all over
 ..........................................................................................  
0 
1 
2 
3 
4 
An1 
I feel listless (“washed out”)
 ..........................................................................................  
0 
1 
2 
3 
4 
An2 
I feel tired
 ..........................................................................................  
0 
1 
2 
3 
4 
An3 
I have trouble starting things because I am tired
 ..........................................................................................  
0 
1 
2 
3 
4 
An4 
I have trouble finishing things because I am tired
 ..........................................................................................  
0 
1 
2 
3 
4 
An5 
I have energy
 ..........................................................................................  
0 
1 
2 
3 
4 
An7 
I am able to do my usual activities
 ..........................................................................................  
0 
1 
2 
3 
4 
An8 
I need to sleep during the day
 ..........................................................................................  
0 
1 
2 
3 
4 
An12 
I am too tired to eat
 ..........................................................................................  
0 
1 
2 
3 
4 
An14 
I need help doing my usual activities
 ..........................................................................................  
0 
1 
2 
3 
4 
An15 
I am frustrated by being too tired to do the things I want 
to do
 ..........................................................................................  
 
0 
 
1 
 
2 
 
3 
 
4 
An16 
I have to limit my social activity because I am tired
 ..........................................................................................  
0 
1 
2 
3 
4 


NCI Protocol #:Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 09/12/2018 
 
73 
 
 


NCI Protocol #:Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 09/12/2018 
 
74 
IIEF Questionnaire 
 
INSTRUCTIONS: These questions ask about your sex life over the past 4 weeks. Please answer the following 
questions as honestly and clearly as possible. In answering these questions, the following definitions apply: 
 
Sexual activity includes intercourse, caressing, foreplay, masturbation, or any other types of sex 
Sexual intercourse is defined as penetration of the partner (you entered your partner) 
Sexual stimulation includes situations like foreplay with a partner, looking at erotic pictures, etc. 
Ejaculate the ejection of semen from the penis (or the feeling of this) 
 
Circle ONLY one answer (number) per question. 
Q1) Over the past 4 weeks, how often were you able to get an erection during sexual activity? 
 
0 = No sexual activity 
 
1 = Almost never / never 
 
2 = A few times (much less than half the time) 
 
3 = Sometimes (about half the time) 
 
4 = Most times (much more than half the time) 
 
5 = Almost always / always 
 
Q2)  Over the past 4 weeks, when you had erections with sexual stimulation, how often were your        erections hard 
enough for penetration? 
 
0 = No sexual activity 
 
1 = Almost never / never 
 
2 = A few times (much less than half the time) 
 
3 = Sometimes (about half the time) 
 
4 = Most times (much more than half the time) 
 
5 = Almost always / always 
 
Q3)  Over the past 4 weeks, when you attempted sexual intercourse, how often were you able to penetrate (enter) your 
partner? 
 
0 = Did not attempt intercourse 
 
1 = Almost never / never 
 
2 = A few times (much less than half the time) 
 
3 = Sometimes (about half the time) 
 
4 = Most times (much more than half the time) 
 
5 = Almost always / always 


NCI Protocol #:Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 09/12/2018 
 
75 
Q4)  Over the past 4 weeks, during sexual intercourse, how often were you able to maintain your erection after you had 
penetrated (entered) your partner?. 
 
0 = Did not attempt intercourse 
 
1 = Almost never / never 
 
2 = A few times (much less than half the time) 
 
3 = Sometimes (about half the time) 
 
4 = Most times (much more than half the time) 
 
5 = Almost always / always 
 
Q5)  Over the past 4 weeks, during sexual intercourse, how difficult was it to maintain your erection to completion of 
intercourse? 
 
0 = Did not attempt intercourse 
 
1 = Extremely difficult 
 
2 = Very difficult 
 
3 = Difficult 
 
4 = Slightly difficult 
 
5 = Not difficult 
Q6)  Over the past 4 weeks, how many times have you attempted sexual intercourse? 
 
0 = No attempts 
 
1 = One to two attempts 
 
2 = Three to four attempts 
 
3 = Five to six attempts 
 
4 = Seven to ten attempts 
 
5 = Eleven+ attempts 
 
Q7)  Over the past 4 weeks, when you attempted sexual intercourse, how often was it satisfactory for you? 
 
0 = Did not attempt intercourse 
 
1 = Almost never / never 
 
2 = A few times (much less than half the time) 
 
3 = Sometimes (about half the time) 
 
4 = Most times (much more than half the time) 
 
5 = Almost always / always 
 
Q8)  Over the past 4 weeks, when you attempted sexual intercourse, how much have you enjoyed sexual intercourse? 


NCI Protocol #:Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 09/12/2018 
 
76 
 
0 = No intercourse 
 
1 = No enjoyment 
 
2 = Not very enjoyable 
 
3 = Fairly enjoyable 
 
4 = Highly enjoyable 
 
5 = Very highly enjoyable 
 
Q9)  Over the past four weeks, when you had sexual stimulation or intercourse, how often did you ejaculate? 
 
0 = No sexual stimulation / intercourse 
 
1 = Almost never / never 
 
2 = A few times (much less than half the time) 
 
3 = Sometimes (about half the time) 
 
4 = Most times (much more than half the time) 
 
5 = Almost always / always 
 
Q10)   Over the past 4 weeks, when you had sexual stimulation or intercourse, how often did you have the feeling of 
orgasm or climax? 
 
0 = No sexual stimulation / intercourse 
 
1 = Almost never / never 
 
2 = A few times (much less than half the time) 
 
3 = Sometimes (about half the time) 
 
4 = Most times (much more than half the time) 
 
5 = Almost always / always 
 
Q11)  Over the past 4 weeks, how often have you felt sexual desire? 
 
1 = Almost never / never 
 
2 = A few times (much less than half the time) 
 
3 = Sometimes (about half the time) 
 
4 = Most times (much more than half the time) 
 
5 = Almost always / always 
 
 
Q12)  Over the past 4 weeks, how would you rate your level of sexual desire? 


NCI Protocol #:Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 09/12/2018 
 
77 
 
1 = Very low / not at all 
 
2 = Low 
 
3 = Moderate 
 
4 = High 
 
5 = Very high 
 
Q13)  Over the past 4 weeks, how satisfied have you been with your overall sex life? 
 
1 = Very dissatisfied 
 
2 = Moderately dissatisfied 
 
3 = About equally satisfied and dissatisfied 
 
4 = Moderately satisfied 
 
5 = Very satisfied 
 
Q14)   Over the past 4 weeks, how satisfied have you been with your sexual relationship with your partner? 
 
1 = Very dissatisfied 
 
2 = Moderately dissatisfied 
 
3 = About equally satisfied and dissatisfied 
 
4 = Moderately satisfied 
 
5 = Very satisfied 
 
Q15)   Over the last 4 weeks, how would you rate your confidence that you could get and keep an erection? 
 
1 = Very low 
 
2 = Low 
 
3 = Moderate 
 
4 = High 
 
5 = Very high 
 


NCI Protocol #:Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 09/12/2018 
 
78 
IPSS - International Prostate Symptom Score 
 
Put an X in the box (beside the number) that most closely corresponds to your response for each question.  
 
1.) Incomplete emptying: Over the past month, how often have you had a sensation of not emptying your 
bladder completely after you finished urinating?  
Not at all 
Less than 1 
time in 5 
Less than half 
the time 
About half the 
time 
More than half 
the time 
Almost always 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
 
2.) Frequency: Over the past month, how often have you had to urinate again less than 2 hours after you 
finished urinating? 
Not at all 
Less than 1 
time in 5 
Less than half 
the time 
About half the 
time 
More than half 
the time 
Almost always 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
 
3.) Intermittency: Over the last month, how often have you found that you stopped and started again several 
times when you urinated? 
Not at all 
Less than 1 
time in 5 
Less than half 
the time 
About half the 
time 
More than half 
the time 
Almost always 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
 
4.) Urgency: Over the last month, how difficult have you found it to postpone urination? 
Not at all 
Less than 1 
time in 5 
Less than half 
the time 
About half the 
time 
More than half 
the time 
Almost always 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
 
5.) Weak-stream: Over the past month, how often have you had a weak urinary stream? 
Not at all 
Less than 1 
time in 5 
Less than half 
the time 
About half the 
time 
More than half 
the time 
Almost always 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
 
6.) Straining: Over the past month, how often have you had to push or strain to begin urination? 
Not at all 
Less than 1 
time in 5 
Less than half 
the time 
About half the 
time 
More than half 
the time 
Almost always 
0 
 
1 
 
2 
 
3 
 
4 
 
5 
 
 
7.) Nocturia: Over the past month, how many times did you typically get up to urinate from the time you went 
to bed until the time you got up in the morning? 
1 time 
2 times 
3 times 
4 times 
5 times 
1 
 
2 
 
3 
 
4 
 
5 
 
 
 
Subject initials and Date: _______________ 
8.) Quality of life due to urinary symptoms 
Delighted 
Pleased 
Mostly 
satisfied 
Mixed – 
about equally 
satisfied and 
dissatisfied 
Mostly 
dissatisfied 
Unhappy 
Terrible 
If you were to spend the rest of your life with your urinary 
condition the way it is now, how would you feel about that? 
0 
1 
2 
3 
4 
5 
6 


NCI Protocol #:Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 09/12/2018 
 
79 
 
FOR STUDY STAFF ONLY 
Total Score___________________  
Note: Only score questions 1-7 
 
1-7 mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic. 
 
 


NCI Protocol #:Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 09/12/2018 
 
80 
 
 
 
This questionnaire is designed to measure Quality of Life issues in patients with Prostate 
cancer.  To help us get the most accurate measurement, it is important that you answer all 
questions honestly and completely. 
 
Remember, as with all medical records, information contained within this survey will remain 
strictly confidential. 
 
 
 
 
 
 
 
 
Today's Date (please enter date when survey completed):  Month 
Day 
Year  
 
 
 
Study ID:    
 
 
 
 
 
EPIC 
 
The Expanded Prostate Cancer Index Composite 


NCI Protocol #:Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 09/12/2018 
 
81 
Page  2 
Do Not Mark in This Space 
 
 
 
 
 
 
1. Over the past 4 weeks, how often have you leaked urine? 
More than once a day ...................... 1 
About once a day ............................. 2 
More than once a week.................... 3 
(Circle one number) 
23/ 
About once a week........................... 4 
Rarely or never.................................. 5 
2. Over the past 4 weeks, how often have you urinated blood?  
More than once a day ...................... 1 
About once a day ............................. 2 
More than once a week.................... 3 
(Circle one number) 
24/ 
About once a week .......................... 4 
Rarely or never ................................. 5 
3. 
Over the past 4 weeks, how often have you had pain or burning with urination?  
More than once a day ...................... 1 
About once a day ............................. 2 
More than once a week.................... 3 
(Circle one number) 
25/ 
About once a week .......................... 4 
Rarely or never ................................. 5 
4. 
Which of the following best describes your urinary control during the last 4 weeks?  
No urinary control whatsoever  ......... 1 
Frequent dribbling..............................2 
(Circle one number) 
26/ 
Occasional dribbling ......................... 3 
Total control ..................................... 4 
 
 
URINARY FUNCTION 
This section is about your urinary habits. Please consider ONLY THE LAST 4 WEEKS. 


NCI Protocol #:Not Applicable 
DF/HCC Protocol #:15-120 
Protocol Version Date: 09/12/2018 
 
82 
EPIC 2.2002 
Copyright 2002. The University of Michigan. All rights reserved.
Page  3 
Do Not Mark in This Space 
 
5. How many pads or adult diapers per day did you usually use to control leakage 
1. during the last 4 weeks? 
 
None ......................................................................... 
0 
1 pad per day..........................................................… 
1 
2 pads per day............................................................ 
2 
(Circle one number) 
3 or more pads per day............................................... 
3 
27/ 
 
 
6. How big a problem, if any, has each of the following been for you during the last 4 weeks? 
(Circle one number on each line) 
 
 
No 
Problem 
Very Small 
Problem 
Small 
Problem 
Moderate 
Problem 
Big Problem 
 
a. Dripping or leaking urine …...... 
0 
1 
2 
3 
4 
28/ 
b. Pain or burning on urination..... 
0 
1 
2 
3 
4 
29/ 
c. Bleeding with urination............. 
0 
1 
2 
3 
4 
30/ 
d. Weak urine stream or incomplete 
emptying……….. 
0 
1 
2 
3 
4 
31/ 
e. Waking up to urinate………….. 
0 
1 
2 
3 
4 
32/ 
f. Need to urinate frequently during 
the day ………………………….. 
0 
1 
2 
3 
4 
33/ 
 
 
 
7. Overall, how big a problem has your urinary function been for you during the last 4 weeks? 
No problem ...................................... .1 
Very small problem .......................... .2 
Small problem..................................... 3 
(Circle one number) 
34/ 
Moderate problem. .......................... .4 
Big problem ..................................... .5 
 
 
 
 
 
 
 
 
 
 
EPIC 2.2002 
                                                                        Copyright 2002. The University of Michigan. All rights reserved. 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #: 15-120 
Protocol Version Date: 09/12/2018 
 
83 
 
Page  4 
 
 
 
 
 
 
 
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8. How often have you had rectal urgency (felt like I had to pass stool, but did not) during 
the last 4 weeks? 
More than once a day ................................. 1 
About once a day ....................................... 2 
More than once a week................................ 3 (Circle one number) 
42/ 
About once a week ..................................... 4 
Rarely or never ............................................. 5 
9. How often have you had uncontrolled leakage of stool or feces? 
More than once a day ................................. 1 
About once a day ....................................... 2 
More than once a week................................ 3 (Circle one number) 
43/ 
About once a week ..................................... 4 
Rarely or never ............................................. 5 
10. How often have you had stools (bowel movements) that were loose or liquid 
(no form, watery, mushy) during the last 4 weeks? 
Never...................................................... 1 
Rarely ..................................................... 2 
About half the time................................... 3 (Circle one number) 
44/ 
Usually ..................................................... 4 
Always ..................................................... 5 
11. How often have you had bloody stools during the last 4 weeks? 
Never. .............................................. 1 
Rarely ............................................... 2 
About half the time............................. 3 (Circle one number) 
45/ 
Usually ............................................... 4 
Always ............................................... 5 
 
BOWEL HABITS 
The next section is about your bowel habits and abdominal 
pain. Please consider ONLY THE LAST 4 WEEKS. 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #: 15-120 
Protocol Version Date: 09/12/2018 
 
84 
EPIC 2.2002 
                                                                        Copyright 2002. The University of Michigan. All rights reserved.
Page  5 
 
 
 
 
 
 
 
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12. How often have your bowel movements been painful during the last 4 weeks? 
Never. .............................................. 1 
Rarely ............................................... 2 
About half the time............................ 3 (Circle one number) 
46/ 
Usually ............................................... 4 
Always ............................................... 5 
13. How many bowel movements have you had on a typical day during the last 4 weeks? 
Two or less. ...................................... 1 
Three to four.......................................2 
(Circle one number) 
47/ 
Five or more ..................................... 3 
14. How often have you had crampy pain in your abdomen, pelvis or rectum during the last 4 weeks? 
More than once a day ....................... 1 
About once a day ............................. 2 
More than once a week..................... 3 
(Circle one number) 
48/ 
About once a week ........................... 4 
Rarely or never .................................. 5 
15. How big a problem, if any, has each of the following been for you? (Circle one number on each line) 
 
a. Urgency to have 
No 
Problem 
Very Small 
Problem 
Small 
Problem 
Moderate 
Problem 
Big 
Problem 
a bowel movement  .................. 
0 
1 
2 
3 
4 
49/ 
b. Increased frequency of 
bowel movements..................... 
0 
1 
2 
3 
4 
50/ 
c. Watery bowel movements......... 
0 
1 
2 
3 
4 
51/ 
d. Losing control of your stools...... 
0 
1 
2 
3 
4 
52/ 
e. Bloody stools ............................ 
0 
1 
2 
3 
4 
53/ 
f. Abdominal/ Pelvic/Rectal pain... 
0 
1 
2 
3 
4 
54/ 
 
 
 
 
EPIC 2.2002 
                                                                        Copyright 2002. The University of Michigan. All rights reserved


NCI Protocol #: Not Applicable 
DF/HCC Protocol #: 15-120 
Protocol Version Date: 09/12/2018 
 
85 
Page  6 
 
 
 
 
 
 
 
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16. Overall, how big a problem have your bowel habits been for you during the last 4 weeks? 
No problem ...................................... 1 
Very small problem .......................... 2 
Small problem.................................... 3 
(Circle one number) 
55/ 
Moderate problem. .......................... 4 
Big problem ..................................... 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EPIC 2.2002 
                                                                        Copyright 2002. The University of Michigan. All rights reserved


NCI Protocol #: Not Applicable 
DF/HCC Protocol #: 15-120 
Protocol Version Date: 09/12/2018 
 
86 
Page  7 
 
 
 
 
 
 
 
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17. How would you rate each of the following during the last 4 weeks? (Circle one number on each line) 
 
Very 
Poor to 
None 
Poor Fair 
Good Very 
Good 
 
a. Your level of sexual desire?....................................... 
1 
2 
3 
4 
5 
56/ 
b. Your ability to have an erection?................................ 
1 
2 
3 
4 
5 
57/ 
c. Your ability to reach orgasm (climax)?....................... 
1 
2 
3 
4 
5 
58/ 
 
18. How would you describe the usual QUALITY of your erections during the last 4 weeks? 
 
None at all......................................................................................... 
1 
Not firm enough for any sexual activity.............................................. 
2 
Firm enough for masturbation and foreplay only............................... 
3 
(Circle one number) 
59/ 
Firm enough for intercourse.............................................................. 
4 
 
19. How would you describe the FREQUENCY of your erections during the last 4 weeks? 
 
I NEVER had an erection when I wanted one................................... 
1 
I had an erection LESS THAN HALF the time I wanted one............. 
2 
I had an erection ABOUT HALF the time I wanted one .................... 3 
(Circle one number) 
60/ 
I had an erection MORE THAN HALF the time I wanted one............ 4 
I had an erection WHENEVER I wanted one..................................... 5 
 
20. How often have you awakened in the morning or night with an erection during the last 4 weeks? 
 
Never …................................................................ 1 
Less than once a week.......................................... 2 
About once a week................................................ 
3 
(Circle one number) 
61/ 
Several times a week.......................…................. 
4 
Daily………………….........................…................. 
5 
 
 
EPIC 2.2002 
                                                                        Copyright 2002. The University of Michigan. All rights reserved
SEXUAL FUNCTION 
The next section is about your current sexual function and sexual satisfaction. Many of 
the questions are very personal, but they will help us understand the important issues 
that you face every day.  Remember, THIS SURVEY INFORMATION IS COMPLETELY 
CONFIDENTIAL. Please answer honestly about THE LAST 4 WEEKS ONLY. 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #: 15-120 
Protocol Version Date: 09/12/2018 
 
87 
Page  8 
 
 
 
 
 
 
 
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21. During the last 4 weeks, how often did you have any sexual activity? 
Not at all ..................................................................1 
 
 
 
 
 
 
22. During the last 4 weeks, how often did you have sexual intercourse? 
Not at all ..................................................................1 
 
 
 
 
 
 
 
23. Overall, how would you rate your ability to function sexually during the last 4 weeks? 
 
Very poor.............................................................. 
1 
Poor...................................................................... 
2 
Fair....................................................................... 
3 
(Circle one number) 
64/ 
Good.................................................................... 
4 
Very good............................................................. 
5 
24. How big a problem during the last 4 weeks, if any, has each of the following been for you? 
(Circle one number on each line) 
 
 
 
 
 
 
 
25. Overall, how big a problem has your sexual function or lack of sexual function been for you during 
the last 4 weeks? 
 
No problem........................................................... 
1 
Very small problem............................................... 2 
Small problem....................................................... 
3 
(Circle one number) 
68/ 
Moderate problem................................................ 
4 
Big problem.......................................................... 
5 
 
EPIC 2.2002 
   Copyright 2002. The University of Michigan. All rights reserved
Less than once a week.......................................... 2 
About once a week................................................ 
3 
(Circle one number) 
62/ 
Several times a week.......................…................. 
4 
Daily………………….........................…................. 
5 
Less than once a week.......................................... 2 
About once a week................................................ 
3 
(Circle one number) 
63/ 
Several times a week.......................…................. 
4 
Daily………………….........................…................. 
5 
No 
Very Small 
Small 
Moderate 
Big 
Problem Problem 
Problem 
Problem 
Problem 
a. Your level of sexual desire........ 
0 
1 
2 
3 
4 
65/ 
b. Your ability to have an erection. 
0 
1 
2 
3 
4 
66/ 
c. Your ability to reach an orgasm. 
0 
1 
2 
3 
4 
67/ 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #: 15-120 
Protocol Version Date: 09/12/2018 
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Page  9 
 
 
 
 
 
 
 
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26. Over the last 4 weeks, how often have you experienced hot flashes?  
More than once a day ....................... 1 
About once a day ............................. 2 
More than once a week....................   3 
(Circle one number) 
69/ 
About once a week ........................... 4 
Rarely or never .................................. 5 
27. How often have you had breast tenderness during the last 4 weeks?  
More than once a day ....................... 1 
About once a day ............................. 2 
More than once a week....................   3 
(Circle one number) 
70/ 
About once a week ........................... 4 
Rarely or never .................................. 5 
28. During the last 4 weeks, how often have you felt depressed?  
More than once a day ....................... 1 
About once a day ............................. 2 
More than once a week....................   3 
(Circle one number) 
71/ 
About once a week ........................... 4 
Rarely or never .................................. 5 
29. During the last 4 weeks, how often have you felt a lack of energy?  
More than once a day ....................... 1 
About once a day ............................. 2 
More than once a week....................  3 
(Circle one number) 
72/ 
About once a week ........................... 4 
Rarely or never .................................. 5 
 
 
 
EPIC 2.2002 
                           Copyright 2002. The University of Michigan. All rights reserved 
 
HORMONAL FUNCTION 
The next section is about your hormonal function.  Please consider ONLY THE LAST 4 WEEKS. 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #: 15-120 
Protocol Version Date: 09/12/2018 
89 
 
Page  9 
 
 
 
 
 
 
 
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30. How much change in your weight have you experienced during the last 4 weeks, if any?  
Gained 10 pounds or more…………..1 
Gained less than 10 pounds …..…….2 
No change in weight………. …..……. 3 
(Circle one number) 
73/  
Lost less than 10 pounds …..…….….4 
Lost 10 pounds or more…….…..……5 
 
 
31. How big a problem during the last 4 weeks, if any, has each of the following been for you? 
(Circle one number on each line) 
 
 
No 
Problem 
Very Small 
Problem 
Small 
Problem 
Moderate 
Problem 
Big 
Problem 
a. 
Hot flashes………...................... 
0 
1 
2 
3 
4 
74/ 
b. 
Breast tenderness/enlargement.. 
0 
1 
2 
3 
4 
75/ 
c. 
Loss of Body Hair...…................. 
0 
1 
2 
3 
4 
76/ 
d. 
Feeling depressed..…................. 
0 
1 
2 
3 
4 
77/ 
e. 
Lack of energy........…................. 
0 
1 
2 
3 
4 
78/ 
f. 
Change in body weight 
0 
1 
2 
3 
4 
79/ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EPIC 2.2002 
 
 
 
Copyright 2002. The University of Michigan. All rights reserved 


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Page  10 
 
 
 
 
 
 
 
Do Not Mark in This Space 
 
 
 
32. Overall, how satisfied are you with the treatment you received for your prostate cancer? 
Extremely dissatisfied ................................................ 1 
Dissatisfied................................................................ 2 
Uncertain....................................................................  3 
(Circle one number) 
80/ 
Satisfied .................................................................... 4 
Extremely satisfied .................................................... 5 
 
 
 
 
 
 
 
 
 
 
THANK YOU VERY MUCH!! 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EPIC 2.2002 
 
 
 
 
Copyright 2002. The University of Michigan. All rights reserved 
 
 
Overall Satisfaction 


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Men’s Sexual Health Questionnaire (MSHQ) 
 
INTRODUCTION: These next questions ask about your urge or desire to have sex with your MAIN PARTNER. 
Some people refer to this as “feeling horny”. In answering these questions, we only want to know about the sexual urges 
you have felt toward your MAIN PARTNER, and not whether you actually had sex. Some of these questions might be 
difficult to answer, but we would appreciate you being as honest as possible. Remember, all of your answers are 
confidential.  
 
 
Do you have a “MAIN PARTNER”? __ Yes __ No 
IF YOU DO NOT HAVE A MAIN PARTNER, PLEASE ANSWER ALL QUESTIONS WITHOUT THE 
REFERENCE TO “MAIN PARTNER” UNLESS OTHERWISE DIRECTED. 
 
1. In the last month, how often have you felt an urge or desire to have sex with your MAIN PARTNER? 
 
Would you say (Check only one): 
__ All of the time 
__ Most of the time 
__ About half of the time 
__ Less than half of the time 
__ None of the time 
 
 
2. In the last month, how would you rate your urge or desire to have sex with your MAIN PARTNER? 
 
(Check only one) 
__ Very high 
__ High 
__ Moderate 
__ Low 
__ Very low or none at all 
 
 
3. In the last month, have you been bothered by your level of sexual desire?  
 
Have you been… (Check only one): 
__ Not at all bothered 
__ A little bit bothered 
__ Moderately bothered 
__ Very bothered 
__ Extremely bothered 
 


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4. Compared to ONE month ago, has your urge or desire for sex with your MAIN PARTNER increased or decreased?  
 
Has it… (Check only one): 
__ Increased a lot 
__ Increased moderately 
__ Neither increased nor decreased 
__ Decreased moderately 
__ Decreased a lot 
 
INTRODUCTION: The next set of questions asks about the sexual activity you have had in the last month. In 
answering these questions, we want to know about all of the sexual activity you have had with your MAIN PARTNER, 
with other partners, or masturbating. By sexual activity, we mean any type of sex you may have had, including 
intercourse, oral sex, or any other sexual activities that could lead to ejaculation or cumming. 
 
5. In the last month, how often have you had sexual activity, including masturbating, intercourse, oral sex, or any 
other type of sex?  
 
(Check only one): 
__ 0 times per month 
__ 1-3 times per month 
__ 4-6 times per month 
__ More than 6 times per month 
__ Daily or almost daily 
 
If your answer is “0” for item 5, please answer the following questions: 
 
A. When was the last time you had sex? (Check only one) 
__1-3 months ago 
__ 4-6 months ago 
__ 7-12 months ago 
__ More than 1 year to 2 years ago 
__ More than 2 years ago 
 
B. What are the reasons you have not had sex? 
- I could not have sex because I could not get an erection: __ Yes __ No 
- I could not have sex because I could not ejaculate or “cum”: __ Yes __ No 
- I had no partner: __ Yes __ No 
 
Other (specify): __________________________________________________ 
 
 
 
 
 
 


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6. Compared to ONE month ago, has the number of times you have had sexual activity increased or decreased?  
 
Would you say it has… (Check only one): 
__ Increased a lot 
__ Increased moderately 
__ Neither increased nor decreased 
__ Decreased moderately 
__ Decreased a lot 
 
7.  In the last month, have you been bothered by these changes in the number of times you have had sexual activity?  
 
Have you been… (Check only one): 
__ Not at all bothered 
__ A little bit bothered 
__ Moderately bothered 
__ Very bothered 
__ Extremely bothered 
 
INTRODUCTION: These next questions deal with various aspects of your ability to have sex. In answering these 
questions, we want to know about all of the sexual activity you have had with your MAIN PARTNER, with other 
partners, or masturbating. By sexual activity, we mean any type of sex you may have had, including intercourse, oral 
sex, or any other sexual activities that could lead to ejaculation or cumming. Some of these questions might be difficult 
to answer. We hope that you can answer as many of them as possible, and be as honest as possible when answering 
them. Please remember that all of your answers are confidential. First, we would like to ask you a few questions about 
your erections, which some people refer to as “hard-ons”.  
 
 
In the last month have you taken Viagra or any similar drugs for problems with your erection?    __  Yes   __ No 
 
 
 
8.  In the last month, without using drugs like Viagra, how often have you been able to get an erection when you 
wanted to?  
 
Would you say… (Check only one): 
__ All of the time 
__ Most of the time 
__ About half of the time 
__ Less than half of the time 
__ None of the time 
__ Used Viagra or similar drug with every sexual encounter 
 
 
 


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9.  In the last month, if you were able to get an erection without using drugs like Viagra, how often were you able to 
stay hard as long as you wanted to?  
 
Would you say… (Check only one): 
__ All of the time 
__ Most of the time 
__ About half of the time 
__ Less than half of the time 
__ None of the time 
__ Used Viagra or similar drug with every sexual encounter 
 
 
10. In the last month, if you were able to get an erection, without using drugs like Viagra, how would you rate the 
hardness of your erection?  
 
Would you say they were… (Check only one): 
__ Completely hard 
__ Almost completely hard 
__ Mostly hard, but can be slightly bent 
__ A little hard, but bends easily 
__ Not at all hard 
__ Used Viagra or similar drug with every sexual encounter 
 
 
 
11. In the last month, if you have had difficulty getting hard or staying hard without using drugs like Viagra, have 
you been bothered by this problem?…  
 
(Check only one): 
__ Not at all bothered/Did not have a problem with erection 
__ A little bit bothered 
__ Moderately bothered 
__ Very bothered 
__ Extremely bothered 
 
 
 
 


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INTRODUCTION: The next section deals with male ejaculation and the pleasure you have with ejaculation. 
Ejaculation or cumming is the release of semen or cum during sexual climax. In answering these questions, we want to 
know about all of your ejaculations when having sexual activity. These could include ejaculations you have had with 
your MAIN PARTNER, as well as with other partners, or ejaculations you could have had when masturbating. 
 
12.  In the last month, how often have you been able to ejaculate or cum when having sexual activity? 
 
(Check only one) 
__ All of the time 
__ Most of the time 
__ About half of the time 
__ Less than half of the time 
__ None of the time/Could not ejaculate 
 
 
13.  In the last month, when having sexual activity, how often have you felt like you were ejaculating or cumming but 
no fluid came out?  
 
Would you say… (Check only one) 
__ All of the time 
__ Most of the time 
__ About half of the time 
__ Less than half of the time 
__ None of the time 
__ Could not ejaculate 
 
 
14.  In the last month, when having sexual activity, how often did you feel that you took too long to ejaculate or cum?  
 
Would you say… (Check only one) 
__ All of the time 
__ Most of the time 
__ About half of the time 
__ Less than half of the time 
__ None of the time 
__ Could not ejaculate 
 
 
15. In the last month, when having sexual activity, how often did you feel that you ejaculated or came faster than you 
would have wanted to?  
 
(Check only one) 
__ All of the time 
__ Most of the time 
__ About half of the time 
__ Less than half of the time 
__ None of the time 
__ Could not ejaculate 


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16.  Compared to ONE month ago, would you say the amount of time it takes from when you first start ejaculating or 
cumming to when you have stopped ejaculating or cumming has...  
 
(Check only one) 
__ Increased a lot 
__ Increased moderately 
__ Neither increased nor decreased 
__ Decreased moderately 
__ Decreased a lot 
__ Could not ejaculate 
 
 
17.  Some men have a medical condition called retrograde ejaculation. Men with this condition say it feels like their 
ejaculation goes backwards into their bladder rather than out through their penis. In the last month, when having 
sexual activity, how often did you feel that your ejaculation or cum was going backwards?  
 
Would you say… (Check only one) 
__ All of the time 
__ Most of the time 
__ About half of the time 
__ Less than half of the time 
__ None of the time 
__ Could not ejaculate 
 
 
18.    In the last month, how would you rate the strength or force of your ejaculation? Would you say it is…  
 
(Check only one) 
__ As strong as it always was 
__ A little less strong than it used to be 
__ Somewhat less strong than it used to be 
__ Much less strong than it used to be 
__ Very much less strong than it used to be 
__ Could not ejaculate 
 
 
19.  In the last month, how would you rate the amount or volume of semen or fluid when you ejaculate? 
 
Would you say it is… (Check only one) 
__ As much as it always was 
__ A little less than it used to be 
__ Somewhat less than it used to be 
__ Much less than it used to be 
__ Very much less than it used to be 
__ Could not ejaculate 
 
 
 


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20.  Compared to ONE month ago, would you say the physical pleasure you feel when you ejaculate or cum has…  
 
(Check only one) 
__ Increased a lot 
__ Increased moderately 
__ Neither increased nor decreased 
__ Decreased moderately 
__ Decreased a lot 
__ Could not ejaculate 
 
 
21. In the last month, when having sexual activity, how much physical pleasure did you have when you were 
ejaculating or cumming?  
 
Would you say… (Check only one) 
__ A great deal 
__ A moderate amount 
__ A slight amount 
__ Very little 
__ None 
__ Could not ejaculate 
 
 
22.   In the last month, when having sexual activity, how pleasurable has the feeling of ejaculating or cumming been?  
 
Would you say… (Check only one) 
__ Very pleasurable 
__ Somewhat pleasurable 
__ Neither pleasurable nor unpleasurable 
__ Somewhat unpleasurable 
__ Very unpleasurable 
__ Could not ejaculate 
 
 
23.  Do you think that the amount of physical pleasure you have when you ejaculate or cum is dependent on the 
amount or volume of your ejaculation?  
 
Would you say it is… (Check only one) 
__ Very dependent 
__ Dependent 
__ Somewhat dependent 
__ Not very dependent 
__ Not at all dependent 
__ Could not ejaculate 
 
 
 
 


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24.  Do you think the amount of physical pleasure you have when you ejaculate or cum is dependent on the strength or 
force of your ejaculation?  
 
Would you say it is… (Check only one) 
__ Very dependent 
__ Dependent 
__ Somewhat dependent 
__ Not very dependent 
__ Not at all dependent 
__ Could not ejaculate 
 
 
25.  In the last month, have you experienced any physical pain or discomfort when you ejaculated or came?  
 
Would you say you have… (Check only one) 
__ No pain at all 
__ Slight amount of pain or discomfort 
__ Moderate amount of pain or discomfort 
__ Strong amount of pain or discomfort 
__ Extreme amount of pain or discomfort 
__ Could not ejaculate 
 
 
26.  In the last month, if you have had any ejaculation difficulties or have been unable to ejaculate or cum, have you 
been bothered by this?  
 
Would you say… (Check only one) 
__ Not at all bothered/ Did not have a problem with ejaculation 
__ A little bit bothered 
__ Moderately bothered 
__ Very bothered 
__ Extremely bothered 
 
 
 


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These next few questions ask about your relationship with your MAIN PARTNER over the last month. Some of these 
questions are about your sexual relationship only, while others are about your general relationship, and not just your 
sexual relationship. SKIP NEXT SIX QUESTIONS IF NO MAIN PARTNER  
 
27.  Generally, how satisfied are you with the overall sexual relationship you have with your MAIN PARTNER? 
 
Would you say you are… (Check only one) 
__ Extremely Satisfied 
__ Moderately Satisfied 
__ Neither Satisfied nor Unsatisfied 
__ Moderately Unsatisfied 
__ Extremely Unsatisfied 
 
 
28.  Generally, how satisfied are you with the quality of the sex life you have with your MAIN PARTNER? 
 
Would you say you are… (Check only one) 
__ Extremely Satisfied 
__ Moderately Satisfied 
__ Neither Satisfied nor Unsatisfied 
__ Moderately Unsatisfied 
__ Extremely Unsatisfied 
 
 
29.  Generally, how satisfied are you with the number of times you and your MAIN PARTNER have sex? 
 
Would you say you are… (Check only one) 
__ Extremely Satisfied 
__ Moderately Satisfied 
__ Neither Satisfied nor Unsatisfied 
__ Moderately Unsatisfied 
__ Extremely Unsatisfied 
 
 
30.  Generally, how satisfied are you with the way you and your MAIN PARTNER show affection during sex? 
 
Would you say you are… (Check only one) 
__ Extremely Satisfied 
__ Moderately Satisfied 
__ Neither Satisfied nor Unsatisfied 
__ Moderately Unsatisfied 
__ Extremely Unsatisfied 
 
 
 
 
 
 


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31.  Generally, how satisfied are you with the way you and your MAIN PARTNER communicate about sex? 
 
Would you say you are… (Check only one) 
__ Extremely Satisfied 
__ Moderately Satisfied 
__ Neither Satisfied nor Unsatisfied 
__ Moderately Unsatisfied 
__ Extremely Unsatisfied 
 
 
32.  Generally, not counting your sexual relationship, how satisfied are you with all other aspects of the relationship 
you have with your MAIN PARTNER?  
 
Would you say you are… (Check only one): 
__ Extremely Satisfied 
__ Moderately Satisfied 
__ Neither Satisfied nor Unsatisfied 
__ Moderately Unsatisfied 
__ Extremely Unsatisfied 
 
 


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Harbor-UCLA 7-day Sexual Function Questionnaire  
 
Psychosexual Daily Questionnaire 
 
 
 
 


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PANAS 
 
This scale consists of a number of words that describe different feelings and emotions. Read each item and then circle the appropriate answer 
next to that word. Indicate to what extent you have felt this way during the past week.  
Use the following scale to record your answers. 
(1) = Very slightly or not 
at all 
(2) = A little 
(3) = Moderately 
(4) = Quite a bit 
(5) = Extremely 
 
 
Very 
slightly or 
not at all 
A little 
Moderately 
Quite a bit 
Extremely 
1. 
Interested 
1 
2 
3 
4 
5 
2. 
Distressed 
1 
2 
3 
4 
5 
3. 
Excited 
1 
2 
3 
4 
5 
4. 
Upset 
1 
2 
3 
4 
5 
5. 
Strong 
1 
2 
3 
4 
5 
6. 
Guilty 
1 
2 
3 
4 
5 
7. 
Scared 
1 
2 
3 
4 
5 
8. 
Hostile 
1 
2 
3 
4 
5 
9. 
Enthusiastic 
1 
2 
3 
4 
5 
10. Proud 
1 
2 
3 
4 
5 
11. Irritable 
1 
2 
3 
4 
5 
12. Alert 
1 
2 
3 
4 
5 
13. Ashamed 
1 
2 
3 
4 
5 
14. Inspired 
1 
2 
3 
4 
5 
15. Nervous 
1 
2 
3 
4 
5 
16. Determined 
1 
2 
3 
4 
5 
17. Attentive 
1 
2 
3 
4 
5 
18. Jittery 
1 
2 
3 
4 
5 
19. Active 
1 
2 
3 
4 
5 
20. Afraid 
1 
2 
3 
4 
5 
 


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Your Health and Well-Being SF-36 
 
For each of the following questions, please select the appropriate response. 
 
1. 
In general, would you say your health is: 
1Excellent 
2Very Good 
3Good 
4Fair 
5Poor 
 
2. 
Compared to one year ago, how would you rate your health in general now? 
1Much better now than one year ago 
2Somewhat better now than one year ago 
3About the same as one year ago 
4Somewhat worse now than one year ago 
5Much worse now that one year ago 
 
3. 
The following questions are about activities you might do during a typical day. Does your health now limit you in 
these activities? If so, how much? 
 
Yes, limited 
a lot 
Yes, limited 
a little 
No, not 
limited at all 
a. Vigorous activities, such as running, lifting heavy objects, 
participating in strenuous sports 
1 
2 
3 
b. Moderate activities, such as moving a table, pushing a vacuum 
cleaner, bowling, or playing golf 
1 
2 
3 
c. Lifting or carrying groceries 
1 
2 
3 
d. Climbing several flights of stairs 
1 
2 
3 
e. Climbing one flight of stairs 
1 
2 
3 
f. Bending, kneeling, or stopping 
1 
2 
3 
g. Walking more than a mile 
1 
2 
3 
h. Walking several hundred yards 
1 
2 
3 
i. Walking one hundred yards 
1 
2 
3 
j. Bathing or dressing yourself 
1 
2 
3 
 


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4. 
During the past 4 weeks, how much of the time have you had any of the following problems with your work or other regular 
daily activities as a result of your physical health? 
 
 
5
 
During the past 4 weeks, how much of the time have you had any of the following problems with your work or other regular 
daily activities as a result of any emotional problems ( such as feeling depressed or anxious).? 
 
 
6. 
During the past 4 weeks, to what extent has your physical health or emotional problems interfered with your normal social 
activities with family friends, neighbors, or groups? 
 
1 Not at all 
2 Slightly 
3 Moderately 
4 Quite a Bit 
5 Extremely 
 
7. 
How much bodily pain have you had during the past 4 weeks? 
 
1 None 
2 Very Mild 3 Mild 
4 Moderate 5 Severe 
6 Very Severe 
 
8. 
During the past 4 weeks, how much did pain interfere with your normal work (including both work outside the home and 
housework)? 
1 None 
2 A little bit 
3 Moderately 
4 Quite a Bit 
5 Extremely 
 
 
 
 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
a. Cut down on the amount of time you spent on 
work or other activities 
1 
2 
3 
4 
5 
b. Accomplished less than you would like 
1 
2 
3 
4 
5 
c. Were limited in the kind of work or other 
activities
1 
2 
3 
4 
5 
d. Had difficulty performing the work or other 
activities (for example, it took extra effort) 
1 
2 
3 
4 
5 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
a. Cut down on the amount of time you spent on 
work or other activities 
1 
2 
3 
4 
5 
b. Accomplished less than you would like 
1 
2 
3 
4 
5 
c. Did work or other activities less carefully than 
usual 
1 
2 
3 
4 
5 
 
 
 
 
 
 


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9. 
These questions are about how you feel and how things have been with you during the past 4 weeks. For each question, please 
give the one answer that comes close to the way you have been feeling 
 
 
 
 
 
 
 
 
 
How much of the time during the past 4 weeks…. 
All of the 
time 
Most of 
the time 
Some of 
the time 
A little of 
the time 
None of 
the time 
a. Did you feel full of life? 
1 
2 
3 
4 
5 
b. Have you been very nervous? 
1 
2 
3 
4 
5 
c. Have you felt so down in the dumps that nothing 
could cheer you up? 
1 
2 
3 
4 
5 
d. Have you felt calm and peaceful? 
1 
2 
3 
4 
5 
e. Did you have a lot of energy? 
1 
2 
3 
4 
5 
f. Have you felt downhearted and depressed? 
1 
2 
3 
4 
5 
g. Did you feel worn out?  
1 
2 
3 
4 
5 
h. Have you been happy? 
1 
2 
3 
4 
5 
i. Did you feel tired? 
1 
2 
3 
4 
5 
10. During the past 4 weeks, how much of the time has 
your physical health or emotional problems 
interfered with your social activities (like visiting 
friends, relatives, etc.) 
1 
2 
3 
4 
5 
11. How TRUE or FALSE is each of the 
following statements for you? 
Definitely 
True 
Mostly 
True 
Don’t 
Know 
Mostly 
False 
Definitely 
False 
a. I seem to get sick a little easier than 
other people 
1 
2 
3 
4 
5 
b. I am healthy as anybody I know 
1 
2 
3 
4 
5 
c. I expect my health to get worse 
1 
2 
3 
4 
5 
d. My health is excellent 
1 
2 
3 
4 
5 


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DISF-SR II 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DEROGATIS INTERVIEW FOR SEXUAL 
 FUNCTION II 
(Male Version) 
 
 
 
 
 
 
 
 
 
 
COPYRIGHT  2002, 2005 by LEONARD R. DEROGATIS 
 
 


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DISF-SR II (M) 
 
NAME:   
 
 
DATE: 
 
      LOCATION  
                 
 
AGE:  
      
EDUCATION: 
 
MAR. STAT: 
ID NO.  
 
 
 
INSTRUCTIONS 
Below are listed a brief set of questions that ask about your sexual thoughts and activities. The questions 
are divided into five sections that ask about different aspects of your sexual experiences. 
Some questions request that you answer in terms of “how often” you engage in certain sexual activities. 
Other questions ask you to report “how intense” some of your sexual experiences are. A third type of question 
inquires about how much you “enjoyed” or were “satisfied” by different aspects of your sexual activities and 
relationship. 
 
For each Section, there are one or more scale definition boxes located alongside the questions. Indicators at 
the tops of the boxes tell you which questions the particular scale definition should be used with. 
 
The inventory is quite brief, so please take your time in answering all the questions. Please circle the scale 
number for each question that best describes your personal experience. If you have any questions, please ask 
the person who gave you the inventory for help or clarification. 
 
 
 
SECTION I – SEXUAL DESIRE 
 
During the last 30 days, or since the last time you completed this inventory, 
 
1.1 
How often did you have thoughts or fantasies 
about sexual, romantic, or erotic situations? 
Questions 1.1 – 1.4 0
 
1 
2 
3 
4 
5 
6 
7 
 
1.2 
How often did you feel sexual desire? 0
 
1 
2 
3 
4 
5 
6 
7 
 
1.3 
How often did you want to be involved in sexual activities? 0
 
1 
2 
3 
4 
5 
6 
7 
 
1.4 
With the partner of your choice, how often did you want to 
have sexual intercourse? 0
 
1 
2 
3 
4 
5 
6 
7 
1.5 
Usually, how strong was your sexual desire? 
 0  
1 
2 
3 
4 
5 
=  Sum of 1.1 thru 1 
 
7= 2 or more times a day 
6= once a day 
5= 4 to 6 times a week 
4= 2 or 3 times a week 
3= once a week 
2= once or twice a month 1= 
less than once a month 0= 
5= intense 
4= very strong 
3= strong 
2= moderate 
1= mild 
0= absent  
Question 1.5 
 


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=0 
SECTION  II – SEXUAL AROUSAL 
During the past 30 days, or since the last time you filled out this inventory, 
 
2.1 
How often did you feel sexually aroused , that is have 
Questions 2.1 – 2.4 
a satisfactory erection with or without your partner? 
0 
1 
2 
3 
4 
5 
6 
7 
 
2.2 
How often did you have a full erection upon awakening In the morning? 
0 
1 
2 
3 
4 
5 
6 
7 
 
2.3 
How often did you have an erection that enabled you to penetrate your 
partner during intercourse? 
0 
1 
2 
3 
4 
5 
6 
7 
 
2.4 
How often were you able to maintain a good erection to your 
satisfaction throughout sexual intercourse? 
0 
1 
2 
3 
4 
5 
6 
7 
Question 2.5 
 
2.5 
Please rate your ability your ability to get and maintain an 
erection during this period? 
0 
1 
2 
3 
4 
5 
 
 
= Sum of 2.1 to 2.5 
 
 
SECTION  III – SEXUAL ACTIVITY 
 
During the last 30 days, or since the last time you filled out this inventory, 
 
3.1 
How often have you engaged in kissing, petting or sexual 
touching with your partner? 
0 
1 
2 
3 
4 
5 
6 
7 
Questions 3.1-3.5 
 
3.2 
How often have you engaged in masturbation? 
0 
1 
2 
3 
4 
5 
6 
7 
 
3.3 
How often have you initiated sexual experiences with your 
partner? 
0 
1 
2 
3 
4 
5 
6 
7 
 
3.4 
How often have you had sexual intercourse that led to orgasm for 
you or your partner? 
0 
1 
2 
3 
4 
5 
6 
7 
 
3.5 
How often have you engaged in other sexual activities that led 
to orgasm for you or your 
partner? 
= Sum 
0 
1 
2 
3 
4 
5 
6 
7 
3.1-3.5 
7= 2 or more times a day 
6= once a day 
5= 4 to 6 times a week 
4= 2 or 3 times a week 
3= once a week 
2= once or twice a month 1= 
less than once a month 0= 
N t t ll
5= excellent 
4= good 
3= fair 
2= weak 
1= very poor  
0=absent 
7= 2 or more times a day 
6= once a day 
5= 4 to 6 times a week 
4= 2 or 3 times a week 
3= once a week 
2= once or twice a month 1= 
less than once a month 0= 
 
COPYRIGHT 2002 by Leonard R. Derogatis, Ph.D. 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #: 15-120 
Protocol Version Date: 09/12/2018 
109 
SECTION  IV – ORGASM 
 
During the last 30 days, or since the last time you filled out this inventory, 
(NOTE: If you did not experience an orgasm during this period circle “0” for these items) 
 
4.1 
How easy was it for you to have an orgasm? 
 
0 
1 
2 
3 
4 
Questions 
4.1, 4.2, 4.3 
4.2 
Typically, how intense were your orgasms? 
 0 
1 
2 
3 
4 
4.3 
How good was the control or timing of your orgasms? 
 0 
1 
2 
3 
4 
4.4 
How often did you experience an orgasm? 
Questions 4.4 and 4.5 
0 
1 
2 
3 
4 
5 
6 
7 
 
4.5 
How often did you experience a sense of relaxation and feeling 
good after orgasm? 
0 
1 
2 
3 
4 
5 
6 
7 
 
 
= Sum of 4.1 to 4.5 
 
SECTION V – SEXUAL SATISFACTION 
 
During the past 30 days, or since the last time you filled out this form, 
5.1 
How satisfied have you been with your sexual relationship with your partner? 
0 
1 
2 
3 
4 
5 
 
5.2 
How satisfied have you been with the emotional Intimacy and closeness you 
have shared with your partner? 
0 
1 
2 
3 
4 
5 
 
5.3 
How satisfied have you been with how often you have had sex? 
0 
1 
2 
3 
4 
5 
 
5.4 
How satisfied have you been with the variety of your sexual experiences? 
0 
1 
2 
3 
4 
5 
 
5.5 
How satisfied have you been with the sexual Sum of enjoyment you have 
experienced with your partner? 
0 
1 
2 
3 
4 
5 
 
 
4= extremely (easy, intense, good)  
3= very 
(easy, intense, good) 
2= moderately (easy, intense, good) 
1= minimally (easy, intense, good) 0= 
not at all     (easy, intense, good) 
7= 2 or more times a day 
6= once a day 
5= 4 to 6 times a week 
4= 2 to 3 times a week 
3= once a week 
2= once or twice a month 1= 
less than once a month 0= 
not at all 
5= highly satisfied 
4= satisfied 
3= somewhat satisfied 
2= somewhat dissatisfied 
1= dissatisfied 
0= highly dissatisfied 
Questions 5.1– 5.5 
= Sum of 
5.1– 5.5 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #: 15-120 
Protocol Version Date: 09/12/2018 
110 
SEXUAL ACTIVITY, INTEREST, AND DESIRE SCALE 
 
The following questions ask about your interest in sexual activities and your sexual desire during the past 7 days. 
The first set of questions are about THINKING about sex, the second set of questions are about BEING SEXUALLY 
AROUSED, and the third set of questions are about SEXUAL ACTIVITY. Please answer the following questions by 
checking the box under the phrase that best describes your answer. In answering these questions, the following 
definition applies: 
Sexual activity includes intercourse, oral sex, caressing, foreplay, and masturbation. 
 
1. Thinking About Sex (But Not Engaging in Sexual Activity) 
During the past 7 days to what 
extent: 
Not at all 
A little bit 
Somewhat Quite a bit 
A great 
deal 
1a …did you THINK about sexual 
activity? 
□ 
□ 
□ 
□ 
□ 
1b …did you FANTASIZE about 
sexual activity? 
□ 
□ 
□ 
□ 
□ 
 
2. Becoming PHYSICALLY Sexually Aroused (But Not Engaging in Sexual Activity)  
During the past 7 days: 
None of 
the time 
Once or 
twice 
A few 
times 
Several 
times 
Many 
times 
2a …when seeing a sexually 
attractive person or seeing 
something sexual (for example a 
picture or a movie), how often did 
you PHYSICALLY FEEL a sense of 
sexual arousal, or a PHYSICAL 
stirring or tingling of arousal? 
□ 
□ 
□ 
□ 
□ 
 
During the past 7 days: 
0 days or 
nights 
1‐2 days or 
nights 
3‐4 days or 
nights 
5‐6 days of 
nights 
7 days 
or 
2b ...how often did you wake up 
from sleeping with an erection 
(either in the morning or in the 
middle of the night) 
□ 
□ 
□ 
□ 
□ 
 
Copyright (C) 2011 Eli Lilly and Company. All rights reserved. Confidential 2/8/11 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #: 15-120 
Protocol Version Date: 09/12/2018 
111 
3. Engaging in Sexual Activity. 
During the past 7 days: 
0 times 
1‐2 times 
3‐4 times 
5‐6 times 
7 or more 
times 
3a …how many times did you 
masturbate? 
□ 
□ 
□ 
□ 
□ 
3b …how many times did you have 
some type of sexual activity with 
another person? 
□ 
□ 
□ 
□ 
□ 
 
 
For the next two questions, please circle the number that corresponds with the way that you felt during the past 
7 days. 
 
1. In general, thinking of everything you’ve thought, said, and done how would you rate your level of interest 
in sex during the last 7 days? 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
interest 
at all 
 
 
 
 
 
 
 
 
 
Extremely 
high 
interest 
 
 
2. How would you rate your level of sexual desire during the last 7 days? 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No desire 
at all 
 
 
 
 
 
 
 
 
 
Extremely 
high desire 
 
 
 
 
 
 
 
 
 
 
 
 
Copyright (C) 2011 Eli Lilly and Company. All rights reserved. Confidential 2/8/11 


NCI Protocol #: Not Applicable 
DF/HCC Protocol #: 15-120 
Protocol Version Date: 09/12/2018 
112 
HYPOGONADISM ENERGY DIARY 
 
For the next 4 questions, thinking about how you feel now, please circle the number under the phrase that 
best describes how much you feel each word or phrase. 
 
1. Right now, how energetic do you feel? 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
energy 
at all 
 
 
 
 
 
 
 
 
 
Full of 
energy 
 
 
 
2. Right now, how tired or exhausted do you feel? 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Extremely 
Not at all 
tired 
tired 
(Totally 
exhausted) 
 
 
 
3. Right now, how lethargic or sluggish do you feel? 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Extremely 
Not at all 
lethargic/ 
lethargic/ 
sluggish 
sluggish 
 
 
 
4. Right now, how focused (able to concentrate) do you feel? 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Not at all 
Extremely 
focused 
focused/ 
 
able to 
 
concentrate 
 
 
Copyright (C) 2011 Eli Lilly and Company. All rights reserved. Confidential 2/8/11