Clinical trial NCT00955929
Conditions: Penile Cancer Erectile Dysfunction Radical Prostatectomy
Keywords: Penis PLACEBO SILDENAFIL CITRATE TRIMIX Bimix Viagra 09-005 Erectile Dysfunction following Bilateral Nerve-Sparing
Sponsor: Memorial Sloan Kettering Cancer Center
Start date: 2009-08-06; Completion date: 2020-12-09
Enrollment: 76 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
When a bilateral nerve-sparing radical prostatectomy (RP) is performed, recovery of erectile function (rigid erections) is reported for up to 80% of patients, who are less than 60 years old. Erectile function recovery is also impacted by patient age, erectile function before surgery, and the length of time after surgery.

Current evidence from studies suggests that developing erections is important, however, these studies have been small, and the evidence is not definite. Animal studies suggest that erection medication (Viagra, Levitra, Cialis) may protect erection tissue, even in the absence of erections. However, the correct treatment plan is unknown. For example, how often does a man need to take sildenafil (Viagra®) to protect his erectile function or to maximize his erectile function recovery? Is only using erection medication enough for erectile function recovery? Would penile injections, which almost ensure production of an erection, be better than using sildenafil (Viagra®), or might a combination be even better at helping recovery of erections? These are types of questions this study might answer.

Detailed description:

Arms: arm 1: Placebo QHS (blinded) and sildenafil 100mgs (open-label) as required for sexual relations. The placebo will be omitted on nights that 100mgs is used. Placebo will start within 24-48 hours post-surgery. arm 2: Patients will be instructed to take sildenafil 50 mg QHS (blinded) except on nights that they are interested in sexual relations, they will then be instructed to use sildenafil 100mgs (open-label) and skip the 50mg dose. Sildenafil treatment will start within 24-48 hours post-surgery. arm 3: Trimix combination (Papavarine 30mg/mL Phentholamine 1mg/mL Prostaglandin E1 10 mcg/mL), at initial dose of 5 units (0.05ml) will be given; the first 2 injections will be done in the MSKCC urology outpatient clinic (if needed, the investigator can determine appropriate amount of injections for patient training).
Interventions: intervention 1: Placebo QHS and sildenafil and questionnaires intervention 2: Sildenafil and questionnaire intervention 3: Trimix combination (Papavarine 30mg/mL Phentholamine 1mg/mL Prostaglandin E1 10 mcg/mmL) and questionnaires
Intervention descriptions: intervention 1: Pts will be offered sildenafil 100 mg to be used before intercourse on an as-required basis. They will be given six 100 mg doses, per month, for a 12-month duration. Each patient in this group will use a placebo pill (blinded) each night, except on a nights that 100mg is taken for the purpose of sexual relations. Patients will be evaluated in the clinic and will complete the questionnaires at baseline (pre-treatment evaluation), 3, 6, 9, 12, 18 and 24 months after the operation. At 12 months postoperatively, all patients will stop treatment. Visits 3, 6, 9, 12, 18, and 24 months will have ±2 week window. intervention 2: Patients will be instructed to take sildenafil 50 mg QHS (blinded) except on nights that they are interested in sexual relations, they will then be instructed to use sildenafil 100mgs (open-label) and skip the 50mg dose. Sildenafil treatment will start within 24-48 hours post-surgery. Patients will be evaluated in the clinic and will complete the questionnaires at baseline (pre-treatment evaluation), 3, 6, 9, 12, 18 and 24 months after the operation. At 12 months postoperatively, all patients will stop treatment. Visits 3, 6, 9, 12, 18, and 24 months will have ±2 week window intervention 3: Intracavernous injections of a trimix combination (Papaverine 30mg/mL Phentholamine 1mg/mL Prostaglandin E1 10 mcg/mL) will be injected three times a week, and sildenafil 50mg taken on the other four (non-injection) nights. Injection therapy can be used for the purpose of sexual relations. Patients will be evaluated in the clinic and will complete the questionnaires at baseline (pre-treatment evaluation), 3, 6, 9, 12, 18 and 24 months after the operation. At 12 months postoperatively, all patients will stop treatment. Visits 3, 6, 9, 12, 18, and 24 months will have ±2 week window.

Protocol documents:
Prot_SAP_000.pdf: 
Memorial Sloan-Kettering Cancer Center 
IRB Protocol 
IRB#: 09-005 A(10) 
 
 
A Randomized Trial of Pharmacological Penile Rehabilitation in the Preservation of 
Erectile Function Following Bilateral Nerve-Sparing Radical Prostatectomy 
 
MSKCC THERAPEUTIC/DIAGNOSTIC PROTOCOL 
 
Principal 
Investigator/Department: 
John Mulhall, MD 
Dept. of Surgery – Urology Service 
Co-Principal 
Investigator(s)/Department: 
Peter Scardino, MD 
Dept. of Surgery – Urology Service 
Investigator(s)/Department: 
James Eastham, MD 
Joseph Narus, DNP 
Dept. of Surgery – Urology Service 
Dept. of Surgery – Urology Service 
 
Raffi Bashlian, NP 
Dept. of Surgery – Urology Service 
 
Andrew Vickers, PhD 
Dept. of Epidemiology and Biostatistics 
 
Manpreet Boparai, PharmD 
Pharmacy 
Consenting 
Professional(s)/Department: 
Brett Carver, MD 
Jonathan Coleman, MD 
James Eastham, MD 
Vincent Laudone, MD 
John Mulhall, MD 
Raul Parra, MD 
Peter Scardino, MD 
Karim Touijer, MD 
Joseph Narus, DNP 
Raffi Bashlian, NP 
Dept. of Surgery – Urology Service 
Dept. of Surgery – Urology Service 
Dept. of Surgery – Urology Service 
Dept. of Surgery – Urology Service 
Dept. of Surgery – Urology Service 
Dept. of Surgery – Urology Service 
Dept. of Surgery – Urology Service 
Dept. of Surgery – Urology Service 
Dept. of Surgery – Urology Service 
Dept. of Surgery – Urology Service 
 
 
Please Note: A Consenting Professional must have completed the mandatory Human 
Subjects Education and Certification Program. 
 
 
 
 
 
 
 
Memorial Sloan-Kettering Cancer Center 
1275 York Ave. 
New York, NY 10021 
 
 
 
Amended: 02/12/13 


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Amended:  02/12/13 
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Table of Contents 
MSKCC THERAPEUTIC/DIAGNOSTIC PROTOCOL ............................................................... 1 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA ................................................................ 3 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS .......................................................................... 5 
3.0 
BACKGROUND AND RATIONALE ............................................................................... 5 
4.1 
OVERVIEW OF STUDY DESIGN/INTERVENTION ..................................................... 8 
4.2 
DESIGN .................................................................................................................. 8 
4.3 
INTERVENTION ................................................................................................... 9 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS ..................................................................... 10 
6.1 
CRITERIA FOR SUBJECT ELIGIBILITY ..................................................................... 11 
6.2 
SUBJECT INCLUSION CRITERIA .................................................................... 11 
6.3 
SUBJECT EXCLUSION CRITERIA ................................................................... 11 
7.0 
RECRUITMENT PLAN (WITH LIMITED WAIVER OF AUTHORIZATION) ........... 12 
8.0 
PRETREATMENT EVALUATION ................................................................................ 13 
9.0 
TREATMENT/INTERVENTION PLAN ......................................................................... 13 
10.0 
EVALUATION DURING TREATMENT/INTERVENTION ......................................... 14 
11.0 
TOXICITIES/SIDE EFFECTS ......................................................................................... 14 
12.0 
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT ............... 15 
13.0 
CRITERIA FOR REMOVAL FROM STUDY ................................................................ 15 
14.0 
BIOSTATISTICS .............................................................................................................. 15 
15.1 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION 
PROCEDURES ............................................................................................................................. 17 
15.2 RESEARCH PARTICIPANT REGISTRATION ................................................... 17 
15.3 RANDOMIZATION ............................................................................................... 18 
16.0 
DATA  MANAGEMENT ISSUES................................................................................... 18 
16.2 
DATA AND SAFETY MONITORING ............................................................... 18 
17.1 
PROTECTION OF HUMAN SUBJECTS ........................................................................ 19 
17.2 
PRIVACY ............................................................................................................. 19 
17.3 SERIOUS ADVERSE EVENT (SAE) REPORTING .............................................. 19 
THE PI’S SIGNATURE AND THE DATE IT WAS SIGNED ARE REQUIRED ON THE 
COMPLETED REPORT. ............................................................................................................. 20 
18.0 
INFORMED CONSENT PROCEDURES ....................................................................... 20 
19.0 
REFERENCE(S) ............................................................................................................... 21 
20.0 
APPENDICES .................................................................................................................. 22 


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1.1 
PROTOCOL SUMMARY AND/OR SCHEMA 
 
The purpose of this study is to define if the use of nightly sildenafil after radical 
prostatectomy results in better erectile function outcomes than nightly placebo for men who 
have undergone this operation. The study is also designed to compare erectile function 
outcomes between men using regular sildenafil and those using regular penile injections. 
Patients undergoing either laparoscopic or open nerve-sparing radical prostatectomy, who 
meet the inclusion and exclusion criteria, will be asked to participate in the study. Patients will 
be randomized into one of the three arms: 
 
1. PRN Sildenafil Arm:  Patients will use sildenafil 100 mg PRN for sexual relations. 
Patients will take placebo (blinded) at night regularly, except on nights when the 
sildenafil 100 mg pill is taken.  There will be 40 patients in this group. 
 
2. Nightly Sildenafil Arm: Patients will use sildenafil 100 mg PRN for sexual relations. 
Patients will take sildenafil 50 mg (blinded) at night regularly, except on nights when 
the sildenafil 100 mg pill is taken. There will be 80 patients in this group. 
 
3. Combination Therapy Arm: Intracavernous injections of a trimix combination 
(Papaverine 30 mg/mL, Phentholamine 1 mg/mL, Prostaglandin E1 10 mcg/mL) will 
be injected three times a week and sildenafil 50 mg taken on the other four (non- 
injection) nights. Injection therapy can be used for the purposes of sexual relations. 
There will be 80 patients in this group. 
 
Patients have the option of consenting either preoperatively or up to 6 weeks postoperatively. 
 
Preoperative consent: Patients will be evaluated in the clinic and will complete the 
questionnaires at baseline (before surgery) and 3, 6, 9, 12, 18, and 24 months postoperatively. 
At 12 months postoperatively, all patients will stop treatment. 
 
 
Preoperative Evaluation/Consent 
Radical Prostatectomy 
Randomization 
Placebo QHS 
Sildenafil Use PRN 
Sildenafil QHS 
Sildenafil Use PRN 
Intracavernosal Injections 3 times/week 
PLUS 
Sildenafil 4 nights/week 
12 month period of treatment 
Analysis @ 
3, 6, 9, 12, 18, 24 months 
postoperatively 


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Postoperative consent: Patients will be evaluated in the clinic and will complete the 
questionnaires retrospectively (after surgery) and 3, 6, 9, 12, 18, and 24 months after starting 
rehab. At 12 months after starting rehab, all patients will stop treatment. 
 
 
 
The estimated time to completion of enrollment is 18-24 months. Patients will be monitored for a 
total of 24 months. Visits 3, 6, 9, 12, 18, and 24 months will have ±2 week window. 
 
Baseline 
3 Months 
(±2 weeks) 
6 Months 
(±2 weeks) 
9 Months 
(±2 weeks) 
12 Months 
(±2 weeks) 
18 Months 
(±2 weeks) 
24 Months 
(±2 weeks) 
Routine Blood Test 
X 
Liver Function Blood 
Test 
X 
X 
X 
X 
X 
X 
Sitting and Standing 
Blood Pressure and 
Pulse 
X 
X 
X 
X 
X 
X 
X 
International Index of 
Erectile Function 
Questionnaire (IIEF) 
X 
X 
X 
X 
X 
X 
X 
Pill Diary/Sexual 
Encounter Diary 
X 
X 
X 
X 
X 
X 
Adverse Event 
Assessment 
X 
X 
X 
X 
X 
X 
Preoperative Evaluation 
Radical Prostatectomy 
Postoperative Consent 
Randomization 
Placebo QHS 
Sildenafil Use PRN 
Sildenafil QHS 
Sildenafil Use PRN 
Intracavernosal Injections 3 times/week 
PLUS 
Sildenafil 4 nights/week 
12 month period of treatment 
Analysis @ 
3, 6, 9, 12, 18, 24 months 
following start of rehab 


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IRB#: 09-005 A(10) 
Amended:  02/12/13 
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2.1 
OBJECTIVES AND SCIENTIFIC AIMS 
 
The objective of this study is to analyze the ability of 3 different pharmacological strategies to 
preserve the ability of men to achieve spontaneous (non-medication assisted) functioning 
erections after bilateral nerve-sparing radical prostatectomy. 
 
Primary End-Point: Difference in the erectile function (EF) domain score of the International 
Index of Erectile Function (IIEF) between the 3 groups at 24 months. 
 
Secondary End-Points: 
• The time to return of spontaneous functional erections 
• The time for patients to respond to oral erectogenic therapy 
• The proportion of patients who have normalization of their erectile function 
(normalization of the EF domain of the IIEF) 
 
3.0 
BACKGROUND AND RATIONALE 
 
It is estimated that 10% of all men presenting with erectile dysfunction (ED) suffer the 
condition, as a result of surgical procedure, typically, radical pelvic surgery. ED is associated 
with a significant decrease in self-esteem, loss of productivity and relationship discord. Many 
treatments that restore erectile function have been demonstrated to increase quality of life for 
both patient and partner. Over the past 10 years there has been a recrudescence in interest in 
clinical and basic scientific research in post-radical prostatectomy erectile dysfunction. Major 
discrepancy exists in the literature regarding postoperative potency rates with spontaneous 
erectile function occurring in 30-80% of patients. Thus, despite the advent of nerve sparing 
techniques a significant percentage of men continue to suffer from erectile impairment 
following this operation. It is estimated that 50,000 men undergo radical prostatectomy in the 
USA alone each year. It has been postulated lately, that the development of transient ED 
following nerve-sparing surgery due to trauma to the cavernous nerve might trigger a process 
of damage to the endothelial and smooth muscle cavernous tissue that in turn can induce 
permanent veno-occlusive ED. Furthermore, preliminary data suggest that the regular erectile 
activity induced by pharmacological agents may translate into improved preservation of 
spontaneous erections following bilateral nerve sparing surgery. 
 
Mechanisms of Post-Prostatectomy Erectile Dysfunction 
 
Mechanistically, post-RP ED may be neurogenic, arteriogenic, venogenic, or mixed vascular 
(arteriovenogenic) in nature.  Neurogenic impotence, while obviously occurring after 
cavernous nerve interruption, may also occur transiently following cavernous nerve traction 
and/or dissection. Even in the hands of expert nerve sparing surgeons, temporary neural 
trauma may occur. It is believed that the primary mechanism of development of arteriogenic 
erectile dysfunction results from transection of the accessory pudendal arteries, and venogenic 
impotence is based upon corporal smooth muscle collagenization and fibrosis and this is most 
probably the result of either apoptosis associated with neural injury and/or disuse atrophy. The 


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Amended:  02/12/13 
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venocclusive mechanism is a major determinant of success with vasoactive therapies, indeed, 
most of the patients failing to respond to erectogenic pharmacologic therapy have venous leak 
contributing to their ED. The venocclusive mechanism is dependent upon appropriate corporal 
smooth muscle expansion with resultant occlusion of the subtunical venules.  Failure to 
expand the corporal smooth muscle adequately because of structural alterations in the tissue 
results in failure to compress the subtunical venules present between the corporal smooth 
muscle and the tunica albuginea resulting in venous leak. Corporal smooth muscle integrity is 
believed to be dependent upon 2 factors, cavernosal tissue oxygenation (as occurs during 
penile erection) and neural integrity (neural injury has been shown to lead to apoptosis and 
corporal smooth muscle fibrosis). 
 
In previous work, Mulhall et al have examined the chronology of venous leak development 
post-radical prostatectomy in patients with excellent preoperative erectile function who 
developed postoperative erectile dysfunction. The incidence of venous leak, (suggestive of 
permanent, irreversible structural damage to the erectile tissue) was 8% less than four months 
postoperatively, 22% four to eight months postoperatively and 50% eight to twelve months 
postoperatively. In this analysis no patient was treated with postoperative pharmacotherapy in 
any regimented fashion. More recent data, from our clinical database, has indicated that the 
post-RP penile vascular status is predictive of return of spontaneous erections, degree of 
erectile rigidity, and response to sildenafil citrate (unpublished to date). The data also indicate 
that the prognosis is poor for the return of functional erections in the presence of abnormal 
end diastolic velocity values. 
 
Rationale for the Use of Nightly Viagra Postoperatively 
 
Sildenafil is a PDE5 inhibitor, which has been shown to be effective in men with erectile 
dysfunction of various etiologies including post-RP. It has also been demonstrated to increase 
the recovery of erectile function after cavernous nerve injury in human and animal models. 
 
Sildenafil citrate (Viagra) enhances the effects of nitric oxide (NO), a signaling molecule that 
has a diverse range of physiological effects in many tissues, including promoting relaxation of 
smooth muscle in the walls of blood vessels and the erectile tissue within the corpora 
cavernosa of penis. The effect of NO on smooth muscle is mediated by cyclic guanosine 
monophosphate (cGMP); sildenafil works by inhibiting the enzyme, cGMP-specific 
phosphodiesterase type 5 (PDE5), that degrades cGMP. Experience has established the role of 
sildenafil citrate in the treatment of erectile dysfunction (ED). The efficacy of sildenafil for 
ED post-radical prostatectomy has been studied. In the seminal publication by Goldstein et al, 
subpopulation analysis suggested a 43% responder rate (GAQ positivity) for this population. 
Since then in numerous prostatectomy specific studies, sildenafil has been identified as a 
useful management strategy to facilitate men resuming sexual relations. 
 
A recent Pfizer sponsored study assessed the utility of daily sildenafil citrate administration on 
the recovery of spontaneous erectile function after radical prostatectomy. In a randomized 
fashion, 25 men were treated with 50 mg daily, 25 with 100 mg daily and 25 were treated with 


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placebo. Therapy was instituted at 4 weeks postoperatively and lasted 38 weeks. Analysis was 
conducted at 48 weeks following RP. The criteria for inclusion were rigorous, patients 
requiring a combined score of 8 from questions 3 and 4 on the IIEF questionnaire as well as at 
least one 55% erection on nocturnal penile tumescence and rigidity analysis. Success was 
defined as preservation of the score of 8 on questions 3 and 4 of the IIEF. No difference was 
seen in the success rate between the 50 mg and 100 mg arm of the study. However, 27% of 
men in the treatment arm compared to 4% of men in the placebo arm had preservation of 
preoperative erectile function. While cavernosal oxygenation may be a contributor to these 
results, most of these patients did not obtain an erection in response to sildenafil early 
postoperatively, thus other factors must be at play. 
 
While much of the attention has been focused on corporal smooth muscle in the study of post 
prostatectomy ED, it is appreciated that the endothelium plays a major role in erection and 
thus maintaining endothelial health following RP may improve long-term spontaneous erectile 
function outcome. Desouza et al utilized flow-mediated dilation (FMD) of a transiently 
occluded brachial arteries as a model assessing nitric oxide dependent endothelial function. In 
their study, 14 patients with both type II diabetes and erectile dysfunction were enrolled. 
Following the baseline measurement of brachial artery width patients received 25 mg 
sildenafil, and an hour later the acute phase FMD was measured. Patients continued sildenafil 
25 mg once daily for 14 weeks. 24 hours after the last sildenafil dose chronic phase FMD was 
measured. In both the acute and chronic phase of treatment patients in the treatment arm had a 
significantly greater FMD than the placebo-controlled group, thus indicating that sildenafil 
enhanced endothelial function. The positive effects of sildenafil on endothelium has been 
confirmed in men with cardiovascular disease. In the laboratory of Dr. Mulhall, daily 
administration of sildenafil in the rat model of cavernous nerve crush injury has resulted in 
better preservation of endothelial staining (using CD31 immunohistochemistry) and reduction 
in apoptotic indices (on TUNEL assay). Unpublished data from Pfizer indicates that sildenafil 
has a positive impact on the PI3/AKT/eNOS pathway. 
 
Rationale for the Use of Regular Intracavernosal Injections Postoperatively 
 
The relationship between hypoxia and cavernosal fibrosis has been documented in several 
studies (11), it is thought that hypoxia induces TGF-beta1 that in turn accelerates 
collagenization of the corpus cavernosum smooth muscle, while at the same time, decreasing 
the level of PGE1 that help protect from fibrosis (12). Since, hypoxia of cavernous tissue is 
related to the blood supply and the greatest blood supply occur at time of erection any neural 
damage that results in ED may expose the cavernous tissues to longer periods of hypoxia. 
Leungwattanakij et al (13) demonstrated in a cavernous neurotomy rat model that sharp neural 
injury resulted in an increase in hypoxia inducible factor-1 (HIF-1alpha) and TGF-beta1 as 
well as increase in cavernous tissue collagen synthesis. In a landmark study, Montorsi et al (5) 
based a study on the assumption that the events of nocturnal erection supply the cavernous 
bodies with oxygenation that might protect them from developing fibrotic changes during the 
transient period of erectile dysfunction following nerve sparing radical prostatectomy. In their 
study they treated patients with 3 weekly intracavernousal injections of Alprostadil. This in 


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turn would ensure that when the erectile function would resume the secondary fibrotic 
changes to the penile tissue would not be sever enough to cause erectile dysfunction on their 
own. In this prospective study 30 patients were enrolled, all potent, all had nerve-sparing RP. 
15 received 3 weekly injections for 15 weeks. 12 completed the treatment. Although the trial 
was small, the difference between treatment and control group was statistically significant. 
(Treatment group - 67% had erections sufficient for intercourse versus. 20% in the Control 
group - p < 0.01) However, to date this is the only randomized evidence supporting the role 
of penile rehabilitation with intracavernosal injections after radical prostatectomy. There is a 
need for a larger confirmatory study particularly using a modality that avoids intracavernosal 
injections. Intracavernosal injection therapy was originally discovered in 1983. In 1985, 
trimix, in the form of papaverine/phentolamine/prostaglandin E1 was introduced. It is 
efficacious in approximately 90% of patients with ED. 
 
4.1 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
 
4.2 
Design 
 
Patients undergoing either laparoscopic or open nerve-sparing radical prostatectomy, who 
meet the inclusion and exclusion criteria described in section 6.0, will be asked to 
participate in the study. Patients will be randomized into one of three arms and assigned a 
study number from CRDB (unrelated to their medical record number): 
 
1. PRN Sildenafil Arm: Patients will be instructed to try and resume their sexual 
life according to their ability; patients interested in using medication for sexual 
activity, will be offered sildenafil 100 mg to be used before intercourse on an as- 
required basis. They will be given six 100 mg doses, per month, for a 12 month 
duration. Each patient in this group will use a placebo pill (blinded) each night, 
except on a night that 100 mg is taken for the purpose of sexual relations. This 
group can be considered to constitute "usual care" as it represents the current 
approach to penile rehabilitation in the community. We estimate, in the first 3 
months, most people will not use sildenafil at all, after this, probably no more 
than once per week on average. The total expected dose in the PRN group is about 
4000 mg over the course of the year. There will be 40 patients in this group. 
 
2. Nightly Sildenafil Arm: Patients will be instructed to take sildenafil 50 mg 
(blinded) at night regularly, even when intercourse is not planned. These patients 
will be instructed to take 100 mg pill on occasions that they are interested in 
sexual relations. On these occasions, they will forego the usual nightly pill. They 
will be given six 100 mg doses, per month, for a 12-month duration. There will be 
80 patients in this group. 
 
3. Combination Therapy Arm: Intracavernous injections of a trimix combination 
(Papaverine 30 mg/mL, Phentholamine 1 mg/mL, Prostaglandin E1 10 mcg/mL) 
will be injected three times a week, and sildenafil 50 mg taken on the other four 


Memorial Sloan-Kettering Cancer Center 
IRB Protocol 
IRB#: 09-005 A(10) 
Amended:  02/12/13 
- 9 - 
 
 
 
(non-injection) nights. Injection therapy can be used for the purpose of sexual 
relations. There will be 80 patients in this group. 
 
Preoperative consent: Patients will be evaluated in the clinic and will complete the 
questionnaires at baseline (before surgery) and 3, 6, 9, 12, 18 and 24 months after 
surgery. At 12 months postoperatively, all patients will stop treatment.  Visits 3, 6, 9, 12, 
18, and 24 months will have ±2 week window. 
 
Postoperative consent: Patients will be evaluated in the clinic and will complete the 
questionnaires retrospectively (after surgery) and 3, 6, 9, 12, 18 and 24 months after 
starting rehab. At 12 months after starting rehab, all patients will stop treatment. Visits 3, 
6, 9, 12, 18, and 24 months will have ±2 week window. 
 
4.3 
Blinding 
 
Preoperative consent: Patients are to be consented and registered as pending prior to their 
surgery. Full registration and randomization will occur immediately following surgery, if 
nerve bundles have been spared. 
 
Postoperative consent: Patients may also consent to the study up to 6 weeks 
postoperatively at which point they will be registered and randomized immediately 
following informed consent in clinic. 
 
The blind 50 mg pills will be taken last thing at night, before the patient goes to bed 
without sexual stimulation (100 mg will be used for sexual relations). Thus, the chances 
of a man having an erection that would “unblind” him is remote. Furthermore, in the first 
9 months after surgery, very few men will respond to any PDE5 inhibitor medication 
because of the intra-operative transient nerve injury. Finally, it takes on average, one hour 
before an erection can occur, and this must be in the setting of sexual stimulation. Thus, 
the patient will likely be asleep at this time. Hence, we believe that patients will remain 
blinded to whether they are on active or placebo sildenafil. Nonetheless, blinding will be 
assessed at the end of the study. 
 
4.4 
Intervention 
 
Three interventions are to be used: 
 
1. PRN Sildenafil Arm: Patients will be instructed to take placebo QHS (blinded) 
except on nights that they are interested in sexual relations, they will then be 
instructed to use sildenafil 100 mg (open-label) and skip the placebo dose.  Placebo 
will start within 24-48 hours after registration. There will be 40 patients in this group. 


Memorial Sloan-Kettering Cancer Center 
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IRB#: 09-005 A(10) 
Amended:  02/12/13 
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2. Nightly Sildenafil Arm: Patients will be instructed to take sildenafil 50 mg QHS 
(blinded) except on nights that they are interested in sexual relations, they will then 
be instructed to use sildenafil 100 mg (open-label) and skip the 50 mg dose. Sildenafil 
treatment will start within 24-48 hours post-surgery. There will be 80 patients in this 
group. 
 
3. Combination Therapy Arm: Trimix combination (Papavarine 30 mg/mL, 
Phentholamine 1 mg/mL, Prostaglandin E1 10 mcg/mL), at initial dose of 5 units 
(0.05 mL) will be given; the first 2 injections will be done in the MSKCC urology 
outpatient clinic (if needed, the investigator can determine appropriate amount of 
injections for patient training). The patients will be instructed, by the sexual medicine 
nurse practitioner, on the technique of injection and dose titration, as well as the 
limitations, contra-indications, side effects and alternatives. The dosing data will be 
entered into electronic medical record or patient medical record by the NP. The dose 
being used cannot be altered by a patient. For safety reasons all dose adjustments are 
conducted by phone with the NP. 
 
For the first 2 weeks after registration, patients will use nightly sildenafil 50 mg 
before commencing penile injections 2 weeks (+3 days) later. Sildenafil treatment 
will start within 24-48 hours after registration. Patients will inject three times per 
week and use sildenafil 50 mg on the other four nights. In this arm, patients will be 
instructed to obtain 3 penetration hardness (≥ 60% rigidity) erections per week. There 
will be 80 patients in this group. 
 
4.5 
Treatment Start Time 
 
Preoperatively: Patients scheduled for Monday-Thursday surgery will begin treatment 
24-48 hours after surgery. Patients scheduled for Monday-Thursday surgery that remain 
in the hospital longer than 24-48 hours for recovery will begin their treatment the night 
they return home. Patients scheduled for Friday and Saturday surgery may have their 
registration completed on Monday to begin treatment Tuesday night. Pharmacy will 
express deliver the medication to the patient’s home if they have been discharged. 
 
Postoperatively: Patients that consent in clinic up to 6 weeks postoperatively will begin 
taking their medication 24-48 hours after being registered and randomized in clinic. 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS 
 
Sildenafil citrate is a PDE5 inhibitor manufactured by Pfizer, who will supply the medication 
as well as its placebo. This medication will be maintained by the MSK pharmacy. 
 
Each site will receive a stipend for the purchase of the intracavernosal vasoactive agent trimix 
combination. This agent is composed of 3 medications: Papaverine 30 mg/mL, Phentholamine 


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1 mg/mL, Prostaglandin E1 10 mcg/mL. The pharmacy will maintain the supply of injection 
medication in a refrigerated state. 
 
6.1 
CRITERIA FOR SUBJECT ELIGIBILITY 
 
6.2 
Subject Inclusion Criteria 
 
• Male, must be ≥ 18 years of age, with histologically confirmed prostate 
adenocarcinoma, that is clinically localized to the prostate gland 
• Stable sexual relationship for ≥ 6 months 
• Open or laparoscopic bilateral nerve-sparing radical prostatectomy 
• Baseline score of ≥ 22 on the International Index of Erectile Function Domain 
(Appendix A) 
• Able to speak, read and write in the English language 
• Calculated creatinine clearance (using the 4 variable MDRD equation based on 
serum creatinine, age, race, and gender) of > 60 cc/min 
• Patient is able to walk up two flights of stairs briskly without chest pain 
• Patient needs to have their baseline sitting AND standing blood pressure and 
pulse done at the time of consent 
 
6.3 
Subject Exclusion Criteria 
 
• Preoperative or planned postoperative pelvic radiation therapy 
• Preoperative or planned postoperative androgen deprivation 
• Presence of Peyronie’s disease at baseline 
• Presence of a penile prosthesis at baseline 
• Resection of one or both nerve bundles at surgery 
• Any contraindications to sildenafil: 
o Patient is currently using nitrates; 
o Presence of retinitis pigmentosa; 
o Presence macular degeneration; 
o MI or CVA within 3 months; 
o Patient is currently using MAOI medications 
• Patient is taking using alpha blockers 
• Patient is taking potent inhibitor of cytochrome P450 CYP3A4 (e.g., 
Ketoconozole) 
• Patient has hepatic impairment 
• Patient has history of substance or alcohol abuse 
• Patient is currently using penile self injection medication (Trimix, Bimix, or PGE- 
1) 
• Patient requiring sildenafil for penetration 
• Use of sildenafil within 30 days of consent 


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7.1 
RECRUITMENT PLAN (WITH LIMITED WAIVER OF AUTHORIZATION) 
 
Potential research subjects will be identified by a member of the patient’s treatment team, the 
protocol investigator, or research team at Memorial Sloan-Kettering Cancer Center (MSKCC).  
If the investigator is a member of the treatment team, s/he will screen their                   
patient’s medical records for suitable research study participants and discuss the study and 
their potential for enrolling in the research study.  Potential subjects contacted by their treating 
physician will be referred to the investigator/research staff of the study. 
 
The principal investigator may also screen the medical records of patients with whom they do 
not have a treatment relationship for the limited purpose of identifying patients who would be 
eligible to enroll in the study and to record appropriate contact information in order to 
approach these patients regarding the possibility of enrolling in the study. 
 
During the initial conversation between the investigator/research staff and the patient, the 
patient may be asked to provide certain health information that is necessary to the recruitment 
and enrollment process.  The investigator/research staff may also review portions of their 
medical records at MSKCC in order to further assess eligibility.  They will use the 
information provided by the patient and/or medical record to confirm that the patient is 
eligible and to contact the patient regarding study enrollment.  If the patient turns out to be 
ineligible for the research study, the research staff will destroy all information collected on the 
patient during the initial conversation and medical records review, except for any information 
that must be maintained for screening log purposes. 
 
In most cases, the initial contact with the prospective subject will be conducted either by the 
treatment team, investigator or the research staff working in consultation with the treatment 
team.  The recruitment process outlined presents no more than minimal risk to the privacy of 
the patients who are screened and minimal PHI will be maintained as part of a screening log. 
For these reasons, we seek a (partial) limited waiver of authorization for the purposes of (1) 
reviewing medical records to identify potential research subjects and obtain information 
relevant to the enrollment process; (2) conversing with patients regarding possible enrollment; 
(3) handling of PHI contained within those records and provided by the potential subjects; and 
(4) maintaining information in a screening log of patients approached (if applicable). 
 
A total of 200 patients will be enrolled. Given that MSK does approximately 850 radical 
prostatectomies annually, we estimate that it will take approximately 18 months to 24 months 
to complete enrollment. Given the baseline erectile function of the general radical 
prostatectomy population, it is likely that approximately 50% of patients will be eligible. 
 
Patients scheduled for nerve-sparing open or laparoscopic RP will be advised of the study. 
Those expressing interest will be screened. If eligible, they will be randomized (see Section 
14.0) to one of the three arms in a 1:2:2 ratio. 


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8.0 
PRETREATMENT EVALUATION 
 
After subjects are assessed for baseline inclusion and exclusion criteria, eligible patients will 
be approached. Only patients meeting all pre and post-operative criteria will be included. 
Patients will complete the IIEF (Appendix A) preoperatively if they consent before surgery or 
retrospectively if they consent after surgery, and must have a score of ≥ 22 on the Erectile 
Function Domain. Patients will have standard blood and urine tests to check the function of 
their organs (e.g. kidney, liver). Patients will also have a sitting and standing blood pressure 
and pulse done. 
 
Preoperative consent: Patients will be registered as pending on the day of consent. 
 
Postoperative consent: Patients will be registered if they consent within 6 weeks after surgery. 
 
After registration, subjects will be randomized into one of the three previously described 
study groups and instructed accordingly. Patients will be given a pill diary/sexual encounter 
diary (Appendix B), drug accountability (Appendix E), and patient instructions sheet 
(Appendix F). Patients will be given enough diaries to capture all study medication use and at 
least 18 sexual attempts. 
 
9.0 
TREATMENT/INTERVENTION PLAN 
 
Patients will be randomized into one of 3 arms as described above, and will be followed up 
for 24 months. Patients will be encouraged to have sexual relations, when comfortable after 
RP. This is ‘usual care’. The use of nightly sildenafil citrate and intracavernosal injection 
therapy is considered investigational, and this study is designed to define whether one, or the 
other, or a combination of these strategies, should become ‘usual care’. Patients routinely 
complete questionnaires after surgery, the only additional requirement for patients will be the 
completion of a pill diary/sexual encounter diary, to delineate the exact utilization of 
medication for sexual relations as well as document all study medication use. Patients will be 
followed at 3, 6, 9, 12, 18, and 24 months. Intervention (placebo, sildenafil or injection) will 
be used for 12 months. Patients will have their sildenafil dose adjusted according to their 
erectile response and side effects (listed in section 11.0). For example, for men responding 
robustly to sildenafil 100 mg may be down-titrated to 50 mg or 25 mg. Likewise, men who 
have side effects (as outlined in Section 11.0) at sildenafil 100 mg will be down-titrated to 50 
mg or 25 mg. If patients are experiencing side effects from daily 50 mg dose, they may down- 
titrated to 25mg, by halving the pill. Intra-cavernosal injection agent dose will be down- 
titrated for penetration hardness erection lasting for greater than 60 minutes or if any side 
effects are seen, as listed in section 11.0. Trimix and Bimix have a 1 month expiration date. 
Combination Therapy Arm patients will be prescribed a total of 3 vials of Trimix or Bimix at 
their 2nd injection training visit and 3, 6, and 9 month protocol visits. The patient will pick up 
1 vial after their appointment and outpatient pharmacy will arrange to have the remaining 2 
vials shipped to the patient at 1 month intervals to cover their treatment plan for a total of 3 
months. 


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10.0 EVALUATION DURING TREATMENT/INTERVENTION 
 
Before treatment (baseline) and 3, 6, 9, 12, 18, and 24 months visits, patients will be evaluated 
in clinic. Patients will be asked for any adverse events, since last visit, and will be given the 
International Index of Erectile Function (IIEF) validated questionnaire (Appendix A), pill 
diary/sexual encounter diary (Appendix B), and drug accountability (Appendix E).  The pill 
diary/sexual encounter diary (Appendix B) and drug accountability (Appendix E) will be 
completed at home. Patients will be given enough diaries to capture at least 18 sexual 
attempts.  At each study visit, the paperwork will be collected and the patient given new 
diaries.  The assigned research professional will review paperwork for any mistakes or 
inconsistencies before patient leaves clinic. Patient’s liver functions will be tested and sitting 
and standing blood pressure, and pulse will be completed at 3, 6, 9, 12, 18, and 24 months 
visits. 
 
The IIEF is the gold standard questionnaire in erectile function assessment. It has been 
validated in numerous languages and has been used for more than a decade now in this field. 
It has 5 domains, one of which is erectile function (the others are libido, orgasm, intercourse 
satisfaction and overall satisfaction). Each question is scored on a 5 point scale, where ‘5’ is 
‘always’ and ‘1’ is ‘never’ and ‘3’ is ‘half the time’, in response to questions pertaining to 
obtaining and maintaining erection.. The pill diary/sexual encounter diary will ask patients to 
record sexual encounters, whether sildenafil or penile injections was used, at what dose, 
whether vaginal penetration occurred, and how they rate their erectile rigidity as well as all 
study medication use. 
 
At 12 months, patients will be instructed to discontinue treatment (that is, either daily pill use 
or injection therapy). They will be permitted to use PRN sildenafil or injections for the 
purpose of sexual relations, prescribed through treating physician. Follow up will continue for 
24 months in total. The administration of the study medications will be monitored by the 
research pharmacy staff to ensure compliance with the protocol, as well as maximizing patient 
safety. 
 
11.1 
TOXICITIES/SIDE EFFECTS 
 
The side effects from each pharmacologic intervention are listed below. Side effects will be 
assessed at each follow-up visit by direct questioning of patients. 
 
Sildenafil: 
 
1. Headache 15% 
2. Flushing of the face 10% 
3. Gastrointestinal upset 7% 
4. Temporary visual changes 2% 
5. Nasal congestion 4%. 


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Trimix and Bimix: 
 
1. PGE1 can induce pain (in up to 30% of patients taking PGE1) 
2. Fibrotic reactions (i.e. subcutaneous nodules, intracavernosal fibrotic areas, have been 
reported). In most cases, penile nodules that occur with injection therapy disappear within 
a few months of stopping. 
3. Ecchymosis 
4. Priapism (0.5-5%). (If not treated right away, permanent damage to the penis could occur). 
Of note, the incidence of priapism in Dr. Mulhall’s practice is less than 0.15%. 
 
12.0 
CRITERIA FOR THERAPEUTIC RESPONSE/OUTCOME ASSESSMENT 
 
Patient outcome will be assessed by the IIEF (International Index of Erectile Function). 
Therapeutic response will be evaluated by comparing the IIEF score for patients in each 
treatment arm at each time point. 
 
13.0 
CRITERIA FOR REMOVAL FROM STUDY 
 
Sildenafil will be stopped should any significant side effects occur or should the patient 
require the use of organic nitrate medications. 
 
Intracavernosal injections will be stopped if the patient develops any fibrotic reactions on the 
penis (except Peyronie’s disease). 
 
The patient can also be removed from this study if they chose to withdraw or the study doctor 
decides it is in the patient’s best interest to remove them from the study if these options are 
appropriate. 
 
14.1 
BIOSTATISTICS 
 
14.2 
Sample Size 
 
For each endpoint we will conduct three analysis: 
 
1. A comparison of nightly sildenafil to PRN sildenafil with an alpha of 2.5% 
2. A comparison of combination treatment to PRN sildenafil with an alpha of 2.5% 
3. A non-inferiority comparison between nightly sildenafil and combination 
treatment: in this analysis, nightly sildenafil will be considered non-inferior to 
combination treatment if the upper bound of a 90% confidence interval for the 
difference between groups does not include combination treatment being at least 
three points superior to nightly sildenafil. 


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Our rationale is for the different comparisons is as follows. We want to know whether the 
two active arms (nightly sildenafil and combination treatment) are superior to control 
(PRN sildenafil). We will therefore test each against control using an alpha half of the 
conventional value to account for multiple testing. Furthermore, combination treatment, 
which involves penile injection, is less tolerable for patients than nightly sildenafil, which 
only involves oral medication. Therefore unless nightly sildenafil is demonstrably 
inferior to combination treatment, we will recommend that injections are not required. 
Hence we will conduct a non-inferiority comparison between the two active arms. 
 
Our primary endpoint is the IIEF-EF at 24 months. Based on previous studies, we 
estimate that the SD for the IIEF-EF will be 9 points. Prior data at MSKCC suggest that 
the correlation between baseline and follow-up IIEF-EF will be small enough as to have a 
negligible effect on variance. The minimum, clinically significant difference between 
active and control arms is 6 points based on our clinical experience and discussion held 
with Raymond Rosen PhD the designer of the IIEF. If we obtain data from 80 patients on 
each of the two active arms (nightly sildenafil and combination therapy) and 40 patients 
on the control arm (PRN sildenafil), we will have 89% power for the comparison 
between active and control and 80% power for the non-inferiority comparison between 
active arms. 
 
MSKCC surgeons do approximately 850 radical prostatectomies per year. We estimate 
that 50% of patients will be eligible for the study. Assuming that 25% - 33% of eligible 
patients enroll, we should complete accrual within 18-24 months. 
 
14.3 
Data Analysis 
 
Summary statistics will be calculated, by group, for age, surgery (open or laparoscopic), 
tumor characteristics (stage, grade, PSA), baseline erectile function and quality of life 
scores. Compliance and off-study use of medications for erectile function will be 
described by group and follow-up time.  Biochemical recurrences will be described 
separately by group using Kaplan-Meier methods. 
 
The primary analysis will compare the erectile function domain score of the IIEF at 24 
months. Secondary endpoints include: 
 
1. EF scores at other time-points 
2. The proportion of patients who have normalization of their erectile function, 
defined as a score of 26 or greater on the EF domain of the IIEF at any point 
during the study 
3. Time for response to sildenafil (as defined by diary) 
4. Time to return of spontaneous functional erections (as defined by diary) 


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The primary comparison and secondary comparison 1 will be made by analysis of co- 
variance with baseline score and randomization strata as the covariates. Secondary 
endpoint 2 will be compared by Fisher's exact test. Secondary endpoints 3 and 4 will be 
compared between groups by log rank. Three pairwise comparisons will be made: nightly 
sildenafil vs. PRN sildenafil; combination treatment vs. PRN sildenafil; nightly sildenafil 
vs. combination treatment. 
 
As an additional analysis, we will model EF scores over time using Generalized 
Estimating Equations with time, treatment, time by treatment and baseline score as 
predictors. Treatment will be entered as two dummy variables: nightly sildenafil (coded 0 
in the PRN group and 1 otherwise) and injection therapy (coded 1 in the combination 
group and 0 otherwise). 
All analyses will be on the intention-to-treat principle with patients analyzed in their 
randomized groups regardless of the treatment actually received. All comparisons 
between combination and PRN sildenafail, and between nightly and PRN sildenafil, will 
use a 2.5% alpha; all comparisons between the two treatment arms will use a 90% non- 
inferiority bound. 
 
The nature, severity and day of onset of adverse effects will be described along with 
assessment of causality. 
 
15.1 
RESEARCH PARTICIPANT REGISTRATION AND RANDOMIZATION 
PROCEDURES 
 
15.2 Research Participant Registration 
 
Confirm eligibility as defined in the section entitled Criteria for Patient/Subject 
Eligibility. 
 
Obtain informed consent, by following procedures defined in section entitled Informed 
Consent Procedures. 
 
During the registration process registering individuals will be required to complete a 
protocol specific Eligibility Checklist. 
 
All participants must be registered through the Protocol Participant Registration (PPR) 
Office at Memorial Sloan-Kettering Cancer Center. PPR is available Monday through 
Friday from 8:30am – 5:30pm at 646-735-8000. Registrations must be submitted via the 
PPR Electronic Registration System (http://ppr/). The completed signature page of the 
written consent/RA or verbal script/RA, a completed Eligibility Checklist and other 
relevant documents must be uploaded via the PPR Electronic Registration System. 


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15.3 Randomization 
 
This is a randomized comparison of PRN sildenafil arm (Group 1), nightly sildenafil 
arm (Group 2), and Combination arm (Group 3). After eligibility has been established 
and immediately after consent has been obtained, patients will be registered to the study 
in the Protocol Participant Registration (PPR) system and randomized using the Clinical 
Research Database (CRDB).  Randomization will be accomplished by the method of 
random permuted blocks with varying block size, stratified by surgeon. A total of 3 
surgeons at MSKCC will perform the nerve sparing RP for a total of 3 strata. 
 
16.1 
DATA  MANAGEMENT ISSUES 
 
A Research Study Assistant (RSA) will be assigned to the study. The responsibilities of the 
RSA include project compliance, data collection, abstraction and entry, data reporting, 
regulatory monitoring, problem resolution and prioritization, and coordinate the activities of 
the protocol study team. 
The data collected for this study will be entered into a secure database. Source documentation 
will be available to support the computerized patient record. 
 
16.2 
Quality Assurance 
 
Weekly registration reports will be generated to monitor patient accruals and 
completeness of registration data.  Routine data quality reports will be generated to assess 
missing data and inconsistencies.  Accrual rates and extent and accuracy of evaluations 
and follow-up will be monitored periodically throughout the study period and potential 
problems will be brought to the attention of the study team for discussion and action 
 
Random-sample data quality and protocol compliance audits will be conducted by the 
study team, at a minimum of two times per year, more frequently if indicated. 
 
16.3 
Data and Safety Monitoring 
 
The Data and Safety Monitoring (DSM) Plans at Memorial Sloan-Kettering Cancer 
Center were approved by the National Cancer Institute in September 2001.  The plans 
address the new policies set forth by the NCI in the document entitled “Policy of the 
National Cancer Institute for Data and Safety Monitoring of Clinical Trials” which can be 
found at: http://cancertrials.nci.nih.gov/researchers/dsm/index.html.  The DSM Plans at 
MSKCC were established and are monitored by the Office of Clinical Research.  The 
MSKCC Data and Safety Monitoring Plans can be found on the MSKCC Intranet at:  
http://mskweb2.mskcc.org/irb/index.htm 
 
 
There are several different mechanisms by which clinical trials are monitored for data, 
safety and quality.  There are institutional processes in place for quality assurance (e.g., 


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protocol monitoring, compliance and data verification audits, therapeutic response, and 
staff education on clinical research QA) and departmental procedures for quality control, 
plus there are two institutional committees that are responsible for monitoring the 
activities of our clinical trials programs.  The committees: Data and Safety Monitoring 
Committee (DSMC) for Phase I and II clinical trials, and the Data and Safety Monitoring 
Board (DSMB) for Phase III clinical trials,  report to the Center’s Research Council and 
Institutional Review Board. 
 
During the protocol development and review process, each protocol will be assessed for 
it’s level of risk and degree of monitoring required. Every type of protocol (e.g., NIH 
sponsored, in-house sponsored, industrial sponsored, NCI cooperative group, etc.) Will 
be addressed and the monitoring procedures will be established at the time of protocol 
activation 
 
17.1 
PROTECTION OF HUMAN SUBJECTS 
 
Inclusion of Children in Research 
 
This protocol/project does not include children because the number of children is limited and 
because the majority are already accessed by a nationwide pediatric cancer research network. 
This statement is based on exclusion 4b of the NIH Policy and Guidelines on the Inclusion of 
Children as Participants in Research Involving Human Subjects. 
 
17.2 
Privacy 
 
MSKCC’s Privacy Office may allow the use and disclosure of protected health 
information pursuant to a completed and signed Research Authorization form.  The use 
and disclosure of protected health information will be limited to the individuals described 
in the Research Authorization form.  A Research Authorization form must be completed 
by the Principal Investigator and approved by the IRB and Privacy Board. 
 
17.3 Serious Adverse Event (SAE) Reporting 
 
Any SAE must be reported to the IRB/PB as soon as possible but no later than 5 calendar 
days. The IRB/PB requires a Clinical Research Database (CRDB) SAE report be 
submitted electronically to the SAE Office at sae@mskcc.org containing the following 
information: 
 
Fields populated from the CRDB: 
 
• Subject’s name (generate the report with only initials if it will be sent outside of 
MSKCC) 
• Medical record number 
• Disease/histology (if applicable) 


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• Protocol number and title 
Data needing to be entered: 
• The date the adverse event occurred 
• The adverse event 
• Relationship of the adverse event to the treatment (drug, device, or intervention) 
• If the AE was expected 
• The severity of the AE 
• The intervention 
• Detailed text that includes the following information: 
o A explanation of how the AE was handled 
o A description of the subject's condition 
o Indication if the subject remains on the study 
o If an amendment will need to be made to the protocol and/or consent form  
The PI’s signature and the date it was signed are required on the completed report. 
18.1 
INFORMED CONSENT PROCEDURES 
 
Before protocol-specified procedures are carried out, consenting professionals will 
explain full details of the protocol and study procedures as well as the risks involved to 
participants prior to their inclusion in the study. Participants will also be informed that 
they are free to withdraw from the study at any time. All participants must sign an 
IRB/PB-approved consent form indicating their consent to participate. This consent form 
meets the requirements of the Code of Federal Regulations and the Institutional Review 
Board/Privacy Board of this Center. The consent form will include the following: 
 
1. The nature and objectives, potential risks and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of 
supportive care for therapeutic studies.) 
4. The name of the investigator(s) responsible for the protocol. 
5. The right of the participant to accept or refuse study interventions/interactions and 
to withdraw from participation at any time. 
 
Before any protocol-specific procedures can be carried out, the consenting professional 
will fully explain the aspects of patient privacy concerning research specific information. 
 
 
In addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 


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Each participant and consenting professional will sign the consent form. The participant 
must receive a copy of the signed informed consent form. 
 
19.0    REFERENCE(S) 
 
(1) Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The international index 
of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. 
Urology 1997; 49(6):822-830. 
 
(2) Karakiewicz PI, Kattan MW, Tanguay S, Elhilali MM, Bazinet M, Scardino PT et al. Cross- 
cultural validation of the UCLA prostate cancer index. Urology 2003; 61(2):302-307. 
 
(3) Rabbani F, Stapleton AMF, Kattan MW, Wheeler TM, Scardino PT. Factors predicting 
recovery of erections after radical prostatectomy. Journal of Urology 2000; 164(6):1929-1934. 
 
(4) Catalona WJ, Carvalhal GF, Mager DE, Smith DS. Potency, continence and complication 
rates in 1,870 consecutive radical retropubic prostatectomies. Journal of Urology 1999; 
162(2):433-438. 
 
(5) Montorsi F, Guazzoni G, Strambi LF, DaPozzo LF, Nava L, Barbieri L et al. Recovery of 
spontaneous erectile function after nerve-sparing radical retropubic prostatectomy with and 
without early intracavernous injections of alprostadil: Results of a prospective, randomized trial. 
Journal of Urology 1997; 158(4):1408-1410. 
 
(6) Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA. Oral sildenafil in 
the treatment of erectile dysfunction. New England Journal of Medicine 1998; 338(20):1397- 
1404. 
 
(7) Harin Padma-Nathan, Beverly hills, Andrew R McCullough, Francois Giuliano, Le Kremlin 
Bicetre, Steven M Toler et al. Postoperative nightly administration of sildenafil citrate 
significantly improves the return of normal spontaneus erectile function after bilateral nerve- 
sparing radical prostatectomy. Joural of Urology 2003; ABS # 100407. 
 
(8) Mitka M. Researchers seek new uses for sildenafil. Jama-Journal of the American Medical 
Association 2003; 289(21):2784-2786. 
 
(9) Desouza C, Parulkar A, Lumpkin D, Akers D, Fonseca VA. Acute and prolonged effects of 
sildenafil on brachial artery flow-mediated dilatation in type 2 diabetes. Diabetes Care 2002; 
25(8):1336-1339. 


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(10) Moreland RB. Is there a role of hypoxemia in penile fibrosis: a viewpoint presented to the 
Society for the Study of Impotence. International Journal of Impotence Research 1998; 
10(2):113-120. 
 
(11) Moreland RB, Traish A, Mcmillin MA, Smith B, Goldstein I, Detejada IS. Pge(1) 
Suppresses the Induction of Collagen-Synthesis by Transforming Growth Factor-Beta(1) in 
Human Corpus Cavernosum Smooth-Muscle. Journal of Urology 1995; 153(3):826-834. 
(12) Daley JT, Watkins MT, Brown ML, Martinez V, Cuevas P, Detejada IS. Prostanoid 
production in rabbit corpus cavernosum .2. Inhibition by oxidative stress. Journal of Urology 
1996; 156(3):1169-1173. 
 
(13) Leungwattanakij S, Bivalacqua TJ, Usta MF, Yang DY, Hyun JS, Champion HC et al. 
Cavernous neurotomy causes hypoxia and fibrosis in rat corpus cavernosum. Journal of 
Andrology 2003; 24(2):239-245. 
 
(14) Lowentritt BH, Scardino PT, Miles BJ, Orejuela FJ, Schatte EC, Slawin KM et al. Sildenafil 
citrate after radical retropubic prostatectomy. J Urol 1999; 162(5):1614-1617. 
 
20.0    APPENDICES 
 
Appendix A: 
IIEF – International Index of Erectile Function 
Appendix B: 
Pill Diary/Sexual Encounter Diary 
Appendix C: 
Patient Handout 
Appendix D: 
Adverse Event Form 
Appendix E: 
Drug Accountability Form 
Appendix F: 
Patient Instruction Sheets