A Study to Evaluate Characteristics Predictive of a Positive Imaging Study for Distant Metastases in Patients With Castration-Resistant Prostate Cancer
Conditions: Castration-Resistant Prostate Cancer
Sponsor: Dendreon

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Clinical Protocol 
 
A STUDY TO EVALUATE CHARACTERISTICS PREDICTIVE OF A 
POSITIVE IMAGING STUDY FOR DISTANT METASTASES IN 
PATIENTS WITH CASTRATION-RESISTANT PROSTATE CANCER 
 
PROTOCOL NUMBER: 
P12-1 
PRODUCT IND NUMBER: 
Not applicable 
CLINICAL PHASE: 
Not applicable 
STUDY PRODUCT: 
Not applicable 
ORIGINAL PROTOCOL ISSUE DATE: 
18 JUL 2013 
AMENDMENT 2 ISSUE DATE: 
01 AUG 2014 
STUDY SPONSOR: 
Dendreon Corporation 
 
1301 Second Ave 
 
Seattle, WA  98101 
 
Medical Monitor 
 
Biostatistician 
 
Clinical Trial Manager 
Candice McCoy, MD 
 
Todd DeVries, PhD 
 
Denise Coffin, BSN, MPA 
(206) 829-1630 (Telephone) 
 
(206) 219-2714 (Telephone) 
 
(206) 829-1550 (Telephone) 
cmccoy@dendreon.com 
 
tdevries@dendreon.com 
 
dcoffin@dendreon.com 
 
24 Hour Contact:  (877) 336-3736 
 
CONFIDENTIALITY STATEMENT 
This document is the property of Dendreon Corporation.  It contains confidential and 
proprietary information belonging to Dendreon; therefore, its use is intended solely for 
physicians, clinical research staff, and contract research organizations (“study personnel”) 
participating in Dendreon-sponsored studies.  Reproduction is authorized for and strictly 
limited to study personnel for Dendreon.  Reproduction for any other purpose is prohibited. 

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PROTOCOL SIGNATURE PAGE 
 
A STUDY TO EVALUATE CHARACTERISTICS PREDICTIVE OF A 
POSITIVE IMAGING STUDY FOR DISTANT METASTASES IN 
PATIENTS WITH CASTRATION-RESISTANT PROSTATE CANCER 
 
Amendment 2 Issue Date:  01 AUG 2014 
 
By signing below, the Principal Investigator agrees to adhere to the protocol as outlined. 
 
Principal Investigator Name:  
_____________________________________ 
Title:  
 
 
 
______________________________________________ 
Address:  
 
 
______________________________________________ 
Address:  
 
 
______________________________________________ 
Address:  
 
 
______________________________________________ 
Phone:  
 
 
 
______________________________________________ 
Email:  
 
 
 
______________________________________________ 
Facsimile:  
 
 
______________________________________________ 
Signature:  
 
 
______________________________________________ 
Date:  
 
 
 
______________________________________________ 
 
 
 
 

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PROTOCOL SYNOPSIS 
Protocol Title:  A Study to Evaluate Characteristics Predictive of a Positive Imaging 
Study for Distant Metastases in Patients with Castration-Resistant Prostate Cancer 
Protocol Number:  P12-1 
Product IND Number:  Not applicable 
Clinical Phase:  Not applicable 
Product, Dosage Form, Route, and Treatment Regimen:  No investigational product 
will be administered as part of this study. 
Reference Product, Dosage Form, Route, and Treatment Regimen:  No reference 
product will be administered as part of this study. 
Primary Objective:  To evaluate characteristics predictive of a baseline imaging study 
positive for distant metastases (M1) in patients with castration-resistant prostate cancer 
(CRPC) and no known M1. 
Secondary Objectives: 
• To characterize the sites of distant metastases by determining the proportion of 
patients with CRPC and no known M1 who receive a diagnosis of soft tissue and/or 
bone metastases at the time of the baseline imaging study. 
• To evaluate characteristics predictive of a future imaging study positive for M1 in 
patients with CRPC and no distant metastases (M0) at baseline. 
Exploratory Objectives: 
• To describe the percentage of patients with CRPC and undiagnosed M1 at baseline. 
• To explore biomarkers predictive of a baseline imaging study positive for M1. 
• To explore biomarkers predictive of a future imaging study positive for M1 in 
patients with M0 CRPC at baseline. 
• To evaluate characteristics predictive of a baseline imaging study positive for M1, as 
detected by different imaging modalities. 
• To evaluate characteristics predictive of a future imaging study positive for M1 in 
patients with M0 CRPC at baseline, as detected by different imaging modalities. 
• To describe prostate cancer treatment practice patterns for patients with M0 CRPC. 
• To evaluate characteristics predictive of metastasis-free survival (MFS) in the 
population of patients with M0 CRPC. 

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• For patients diagnosed with M1 CRPC: 
• To describe the timing and sequence of prostate cancer interventions. 
• To describe changes in serum prostate-specific antigen (PSA) values, PSA 
progression, and PSA progression-free survival. 
• To quantify overall survival (OS) from time of diagnosis with M1 CRPC. 
• To evaluate characteristics predictive of OS. 
Study Design and Duration: 
This is a study to evaluate characteristics predictive of an imaging study positive for M1 in 
patients with CRPC.  The study will include 2 phases (M0 Phase and M1 Phase) in which 
patients are characterized by the absence or presence, respectively, of M1.  The study design 
is illustrated below. 
 
 

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a 
Every 6 months, starting from date of the patient’s registration, until 3 years after the last patient is 
registered: ECOG performance status; current opioid analgesic use (yes/no); pain status; prostate cancer 
interventions; survival status; imaging studies (if needed); clinical laboratory tests, including serum PSA values; 
safety events; and biomarkers (AOR); all such data that have become available since the previous visit will also 
be collected. 
b 
Every 6 months until 5 years after the last patient is registered: ECOG performance status; new sites of 
metastases; current opioid analgesic use (yes/no); prostate cancer interventions; survival status; clinical 
laboratory results, including serum PSA; and safety events; all such data that have become available since the 
previous time point for data collection will be collected. 
Baseline 
The patient population consists of patients with CRPC and no known M1.  The patient will 
XQGHUJRWKHEDVHOLQHYLVLW 28 days after written informed consent is obtained.  Baseline 
assessments will include demographics and medical history; date of diagnosis with CRPC, 
with confirming serum PSA values and associated hormonal therapy; prostate cancer imaging 
study history; Eastern Cooperative Oncology Group (ECOG) performance status; height and 
weight; Adult Comorbidity Evaluation-27 (ACE-27); Gleason score; serum PSA history; 
current opioid analgesic use (yes/no); concomitant medications; pain status (with Brief Pain 
Inventory [BPI]); documentation of prior and ongoing prostate cancer interventions; and 
imaging studies (bone and soft tissue) to determine M1 disease status.  In addition, blood 
samples will be collected for clinical laboratory tests (alkaline phosphatase, hemoglobin, 
lactate dehydrogenase [LDH], serum albumin, serum PSA, and testosterone), and for 
additional optional research (AOR), if patient provides consent, for biomarkers potentially 

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predictive of treatment effects, or prognostic for MFS, OS, or an imaging study positive for 
metastatic disease.   
Patients who have undergone an imaging study to determine the presence of M1 (bone and/or 
soft tissue) ≤ 3 months prior to signing the informed consent form are not eligible.  However, 
these patients may enter the study > 3 months after their last imaging study if at that time they 
meet all eligibility criteria.  Patients who are deemed eligible on the basis of 
inclusion/exclusion criteria will be registered in the trial and receive a unique identifier at that 
time.   
Patients with baseline imaging studies confirming M0 CRPC will be entered into the M0 
Phase.  Patients with a baseline imaging study indicating previously unknown M1 will be 
entered into the M1 Phase. 
M0 Phase   
During the M0 Phase, there are 2 types of visits.  Post-baseline imaging studies are not 
required in the M0 Phase and are performed if the investigator determines imaging study(ies) 
is/are needed to assess development of metastases (M1 CRPC).  Depending on the timing of 
an imaging study, its results may be recorded as part of the 6-month M0 Phase study visit or 
part of an M0 Phase imaging visit, as described below: 
• 6-month M0 Phase study visit: A scheduled 6-month M0 Phase study visit (office visit), 
will occur every 6 months (± 1 month), starting from the date of the patient’s registration, 
until 3 years after the last patient is registered.  Any imaging study that occurs within 
1 month of a 6-month M0 Phase study visit will be considered part of that 6-month M0 
Phase study visit, and no repeat study assessments will be required. 
• M0 Phase imaging visit: This visit occurs if, outside of the 1-month window for the 6-
month M0 Phase study visit, the investigator determines imaging study(ies) is/are needed 
to assess development of metastases (M1 CRPC). 
The choice of imaging modality will depend on the study site’s standard of care; the same 
modality should be used for all images for a given patient until diagnosis of M1 CRPC.  
However, if the modality is changed to one with greater sensitivity (e.g., Tc 99m to NaF 
PET/CT or MRI) and diagnosis of M1 CRPC occurs at first use of a new imaging modality, 
an additional imaging study with the previous modality will be performed within 1 month 
after the positive imaging study; this additional imaging study will be reimbursed by the 
sponsor.  However, if the modality is changed to one with lower sensitivity, an imaging study 
with the previous higher modality will not be performed. 
Assessments for both types of M0 Phase visits include: ECOG performance status, current 
opioid analgesic use (yes/no), pain status (with BPI), prostate cancer interventions since the 
previous visit, survival status, blood samples for clinical laboratory tests (alkaline 

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phosphatase, hemoglobin, LDH, serum albumin, and serum PSA) and for AOR (if patient has 
consented to AOR), and safety events (serious adverse events [SAEs], see Safety Measures, 
below); all such data that have become available since the previous visit will also be 
collected. 
M1 Phase 
M1 Phase is observational.  Patients will enter M1 Phase when diagnosed with M1 CRPC at 
registration or at any M0 Phase study visit.  Patients identified with an imaging study positive 
for M1 disease anytime during the M0 Phase will enter M1 Phase and begin following the 
schedule of assessments for M1 Phase starting at the next 6-month visit.  For those patients 
who enter M1 Phase because of a positive imaging study during M0 Phase, an ACE-27 is 
required to be completed within 6 months after the patient’s last M0 Phase visit. 
During M1 Phase, data will be collected (via clinic visits, reviews of the patient’s medical 
record, and/or telephone calls) every 6 months (±1 month) until 5 years after the last patient is 
registered.  At each 6-month time point during M1 phase, all data that have become available 
since the previous time point will be collected regarding ECOG performance status, new sites 
of metastases, current opioid analgesic use (yes/no), prostate cancer interventions, survival 
status, clinical laboratory (alkaline phosphatase, hemoglobin, LDH, serum albumin, and 
serum PSA) data, and safety events (SAEs, see Safety Measures, below). 
In interventional clinical trials, the Prostate Cancer Working Group currently recommends 
measurement of serum PSA levels every 3 or 4 weeks and computed tomography (CT) or 
magnetic resonance imaging (MRI) every 12 weeks to assess disease progression  
(Scher 2008).  During M1 Phase, the sponsor anticipates patients will be monitored similarly.  
The sponsor acknowledges that each M1 Phase patient will receive care appropriate for the 
treatment being administered and the standard of care in the investigator’s clinical practice.  
At each 6-month time point for data collection during M1 Phase, all prostate cancer 
interventions administered during the prior 6-month period, including indication(s) for choice 
of therapy, starting dose, timing (start and stop dates), and rationale for starting and stopping 
therapy (e.g., PSA progression), will be recorded on the electronic case report form (eCRF). 
The anticipated duration of the study is up to 7 years, including 2 years for accrual and up to  
5 years for follow-up after the last patient is registered. 
Sample Size and Population:  A minimum of 2000 patients with CRPC and no known M1 
and who are at least 18 years old at baseline will be registered for study participation. 
Safety Measures: 
The collection of adverse events (AE) will be limited to SAEs in patients who receive at least 
1 partial (> 0 mL) infusion of Provenge® (sipuleucel-T) during the study and that occur at any 

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time from the first infusion through 30 days after the last infusion, regardless of relationship 
to Provenge. 
Any patient who is not diagnosed with M1 CRPC and receives at least 1 partial (> 0 mL) 
infusion of Provenge during the study will be withdrawn from the study.  Serious adverse 
events that occur in such patients will be recorded as described above. 
For patients who withdraw consent or are determined to be lost to follow-up, the investigator 
will use the National Death Index (NDI) or Social Security Death Index (SSDI) to ascertain 
any deaths not reported in the study.  The date of death, when available, will be recorded. 
Statistical Considerations: 
The primary analysis population will include all patients registered in the study who undergo 
a baseline imaging study.  Patients with M0 or M1 CRPC at baseline (M0 or M1 populations, 
respectively) will form additional analysis populations to address different questions of 
interest. 
The primary endpoint for the study will be the occurrence of an imaging study at baseline that 
is positive for M1 (yes or no) among all patients enrolled with a baseline imaging study.  
Logistic regression analyses will be used to analyze the primary endpoint.  With 1000 
patients at each of the 2 possible levels of a binary variable, for a total of 2000 patients, a 
variable is detectable with an odds ratio of 1.312 with 80% power using a 2-sided test at 
alpha = 0.05, assuming an imaging study positive for M1 at baseline in 34.95% and 29.05% 
of patients in level 1 and level 2 of a binary variable, respectively. 
Logistic regression analyses similar to those described for the primary endpoint will be used 
to assess most secondary endpoints.  Appropriate methods accounting for the correlation of 
multiple studies for a patient, such as generalized estimating equations, will be used for these 
analyses.  Cox regression analyses incorporating information on the time to occurrence of a 
positive imaging study will be performed to supplement these analyses. 
In this study, the collection of AEs will be limited to SAEs in those patients who have 
received Provenge.  These events will be summarized and listed by the Medical Dictionary 
for Regulatory Activities (MedDRA) preferred term within each system organ class. 
No formal interim analysis is planned for this study. 
 
 

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TABLE OF CONTENTS 
PROTOCOL SIGNATURE PAGE ........................................................................................2 
PROTOCOL SYNOPSIS ........................................................................................................3 
1.0 
INTRODUCTION......................................................................................................13 
1.1 
Background ......................................................................................................13 
1.2 
Study Rationale ................................................................................................13 
2.0 
ETHICAL CONSIDERATIONS ..............................................................................14 
2.1 
Informed Consent.............................................................................................14 
2.2 
Institutional Review Board ..............................................................................15 
3.0 
STUDY OBJECTIVES ..............................................................................................15 
3.1 
Primary Objective ............................................................................................15 
3.2 
Secondary Objectives.......................................................................................15 
3.3 
Exploratory Objectives ....................................................................................15 
4.0 
INVESTIGATIONAL PLAN ...................................................................................16 
5.0 
STUDY POPULATION ............................................................................................19 
5.1 
Inclusion Criteria .............................................................................................20 
5.2 
Exclusion Criteria ............................................................................................20 
5.3 
Removal of Patients from the Study ................................................................21 
6.0 
TREATMENTS..........................................................................................................21 
7.0 
STUDY ASSESSMENTS AND PROCEDURES ....................................................21 
7.1 
Baseline Visit ...................................................................................................21 
7.2 
Registration ......................................................................................................22 
7.3 
Scheduled 6-Month M0 Phase Study Visit ......................................................23 
7.4 
M0 Phase Imaging Visits .................................................................................23 
7.5 
M1 Phase Data Collection ...............................................................................24 
7.6 
Procedures and Assessments............................................................................28 
7.6.1 
Demographics and Medical History ...............................................28 
7.6.2 
Date of Diagnosis with CRPC ........................................................28 
7.6.3 
Prostate Cancer Imaging Study History ..........................................28 
7.6.4 
Eastern Cooperative Oncology Group Performance Status ............29 
7.6.5 
New Sites of Metastases..................................................................29 
7.6.6 
Height and Weight ..........................................................................29 
7.6.7 
Adult Comorbidity Evaluation ........................................................29 
7.6.8 
Gleason Score..................................................................................29 
7.6.9 
Prostate-specific Antigen History ...................................................29 
7.6.10 
Current Opioid Analgesic Use ........................................................29 

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7.6.11 
Concomitant Medications ...............................................................29 
7.6.12 
Pain Status .......................................................................................30 
7.6.13 
Prostate Cancer Interventions .........................................................30 
7.6.14 
Survival Status ................................................................................30 
7.6.15 
Imaging Studies ...............................................................................30 
7.6.16 
Clinical Laboratory Tests ................................................................31 
7.6.17 
Additional Optional Research for Biomarkers ................................32 
7.6.18 
Serious Adverse Events...................................................................32 
8.0 
STATISTICAL METHODS .....................................................................................34 
8.1 
Sample Size Considerations .............................................................................34 
8.2 
General Considerations ....................................................................................34 
8.2.1 
Analysis Populations .......................................................................34 
8.2.2 
Interim Analysis ..............................................................................34 
8.2.3 
Control Groups ................................................................................35 
8.3 
Analysis of Endpoints ......................................................................................35 
8.3.1 
Primary Endpoint ............................................................................35 
8.3.2 
Secondary Endpoints .......................................................................36 
8.3.3 
Exploratory Endpoints ....................................................................36 
8.4 
Safety Events ...................................................................................................38 
8.5 
Demographic and Baseline Characteristics .....................................................38 
8.6 
Patient Disposition ...........................................................................................38 
8.7 
Concomitant Medications ................................................................................38 
9.0 
REGULATORY REQUIREMENTS .......................................................................38 
9.1 
Pre-Study Documentation ................................................................................38 
9.2 
Investigator Obligations ...................................................................................39 
9.3 
Patient Confidentiality .....................................................................................39 
10.0 
PROTOCOL MANAGEMENT AND ADMINISTRATIVE 
CONSIDERATIONS .................................................................................................39 
10.1 
Study Documentation.......................................................................................39 
10.2 
Data Collection ................................................................................................40 
10.3 
Protocol Interpretation and Compliance ..........................................................40 
10.4 
Study Monitoring .............................................................................................40 
10.5 
Quality Assurance ............................................................................................40 
10.6 
Disclosure of Data and Publication..................................................................41 
11.0 
REFERENCES ...........................................................................................................42 
 

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LIST OF TABLES 
Table 1: 
Schedule of Assessments—M0/M1 Phases .........................................26 
 
LIST OF FIGURES 
Figure 1: 
Study Design ........................................................................................17 
 
LIST OF APPENDICES 
Appendix 1: 
ECOG Performance Status Criteria .....................................................44 
Appendix 2: 
Adult Comorbidity Evaluation-27 .......................................................45 
Appendix 3: 
Brief Pain Inventory .............................................................................47 
 
 
 
 

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LIST OF ABBREVIATIONS AND TERMS 
Abbreviation 
Definition 
AE 
adverse event 
ACE-27 
Adult Comorbidity Evaluation-27 
ADT 
androgen deprivation therapy 
AOR 
additional optional research 
BMI 
body mass index 
BPI 
Brief Pain Inventory 
CAB 
combined androgen blockade 
CFR 
Code of Federal Regulations 
CRPC 
castration-resistant prostate cancer 
CT 
computed tomography 
ECOG 
Eastern Cooperative Oncology Group 
EDC 
electronic data capture 
eCRF 
electronic case report form 
18F-NaF 
sodium fluoride F 18 
FDA 
Food and Drug Administration 
GCP 
good clinical practice 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IND 
investigational new drug 
IRB 
institutional review board 
LDH 
lactate dehydrogenase 
LHRH 
luteinizing hormone-releasing hormone 
M0 
no distant metastases 
M1 
distant metastases 
MedDRA 
Medical Dictionary for Regulatory Activities 
MFS 
metastasis-free survival 
MRI 
magnetic resonance imaging 
NDI 
National Death Index 
OS 
overall survival 
PET 
positron emission tomography 
PSA 
prostate-specific antigen 
PSADT 
PSA doubling time 
RP 
radical prostatectomy 
SAE 
serious adverse event 
SSDI 
Social Security Death Index 
99mTc 
technetium Tc 99m 
US 
United States 
 

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1.0 
INTRODUCTION 
1.1 
Background 
In the United States (US), prostate cancer is the most common malignancy in men.  It 
accounted for approximately 241,740 new cases and approximately 28,170 deaths in 2012 
(Siegel 2012). 
At the time of diagnosis, most patients with prostate cancer have clinically localized disease 
with no distant metastases (M0) (Siegel 2012).  However, despite radical prostatectomy (RP) 
or radiation therapy given with curative intent, 20% to 40% of patients eventually experience 
biochemical recurrence and subsequently receive androgen deprivation therapy (ADT)  
(Ward 2005).  Although ADT leads to tumor control or regression in 80% to 85% of patients 
(Crawford 1989, Schellhammer 1997, Scher 1993), virtually all patients thus treated 
eventually develop castration-resistant prostate cancer (CRPC), which is often followed by 
disease progression and development of distant metastases (M1) in bones and/or lymph nodes 
(Scher 1996, Small 1997). 
1.2 
Study Rationale 
Historically, technetium Tc 99m (99mTc) bone scintigraphy has been the standard method for 
first detection of bone metastases, and Taxotere® (docetaxel)-based chemotherapy was the 
only therapeutic option offering an overall survival (OS) advantage for patients with M1 
CRPC.  However, advances have recently been made in both detection and treatment of 
patients with M1 CRPC.  Imaging technologies such as sodium fluoride F 18 (18F-NaF), 
positron emission tomography (PET) / computed tomography (CT), and magnetic resonance 
imaging (MRI) have shown improved sensitivity and specificity compared to 99mTc 
scintigraphy and may lead to earlier detection of M1 disease than was previously possible 
(Even-Sapir 2006). 
Novel treatments have recently been approved by the US Food and Drug Administration 
(FDA) for patients with M1 CRPC.  They include Provenge® (sipuleucel-T) and Zytiga® 
(abiraterone acetate) for asymptomatic or minimally symptomatic disease; Xtandi® 
(enzalutamide) and Jevtana® (cabazitaxel) for treatment following docetaxel therapy; and 
Xofigo® (radium Ra 223 dichloride) for patients with symptomatic bone metastases. 
Because there are many new therapies for M1 CRPC, including those indicated when no or 
minimal symptoms are present, and multiple imaging study modalities are available, clear 
guidance on the best timing, frequency, and imaging study modality for detecting M1 CRPC 
is essential. 
Most clinicians use disease parameters such as serum prostate-specific antigen (PSA) levels 
and PSA doubling time (PSADT) to assess the risk of metastatic disease in individual patients 
and to make informed decisions regarding when to perform imaging studies (Kane 2003).  
Recently, however, Yu et al (2012) found that 32% of 2577 patients screened for a trial 

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enrolling patients with M0 CRPC did, in fact, have M1 CRPC at screening.  These results 
indicate that M1 disease in patients with CRPC may be underdiagnosed. 
Although serum PSA and PSADT have been shown to convey the relative risk of developing 
M1 disease (Smith 2005), other biomarkers may more accurately predict a positive imaging 
study (Brown 2010).  Interactions between blood cells and distant metastatic cells may alter 
the gene expression profiles of circulating cells (Ross 2012).  Recent studies have shown 
gene expression profiling of blood cells offers a minimally invasive approach that may be 
prognostic for OS and the various prostate cancer disease states, including development of 
M1 CRPC (Olmos 2012).  Therefore, as additional optional research (AOR) in this study, 
blood samples will be collected at baseline and each M0 Phase visit to explore changes in 
gene expression profiles and their correlation with development of M1 disease. 
The primary purpose of this research is to describe patient characteristics predictive of an 
imaging study positive for M1 in the population of patients with CRPC and no known M1.  
These data will contribute to clinical guidance regarding the timing and utility of imaging 
studies in patients with CRPC. 
2.0 
ETHICAL CONSIDERATIONS 
The investigator will conduct the study in compliance with the Declaration of Helsinki, the 
International Conference on Harmonisation (ICH) E6 Guideline for Good Clinical Practice 
(GCP) and the FDA Guidance for Industry:  Good Pharmacovigilance Practices and 
Pharmacoepidemiologic Assessment.  The investigator will follow all relevant national, state, 
and local laws. 
2.1 
Informed Consent 
The investigator is responsible for ensuring that all patients are clearly and fully informed 
about the purpose, potential risks, and other critical issues regarding this study, including 
their right to withdraw at any time. 
Prior to undergoing any study assessments or procedures, all patients must provide written 
informed consent by signing the Informed Consent Form (ICF).  The investigator or designee 
will provide a full explanation of the study and allow the patient to read the ICF and ask any 
questions that may arise.  The patient will be given sufficient time to properly consider the 
information and to make an informed decision prior to signing the ICF.  The investigator or 
designee will document the written informed consent process in the patient’s medical record 
or progress notes and will provide a copy of the signed ICF to the patient. 
The ICF, including any amendments, must be reviewed and approved by Dendreon staff or 
designees and then by the designated Institutional Review Board (IRB) prior to use in the 
study. 

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If an amendment to the protocol changes the patient participation schedule in scope or 
activity, or increases the potential risk to the patient, the ICF will be revised and submitted to 
the IRB for review and approval.  The revised ICF should be used to obtain consent from 
patients currently participating in the study if the information is relevant, or per the IRB’s 
instructions.  The revised ICF will be used to obtain consent from any new patient who is 
enrolled in the study after the approval date of the amendment. 
2.2 
Institutional Review Board 
The investigator is responsible for ensuring that this protocol and relevant supporting data are 
submitted to the appropriate IRB for review and approval before the study can be initiated.  
Dendreon or its designee must receive a letter documenting the IRB approval prior to 
initiation of the study.  Amendments to the protocol will also be submitted to and approved 
by the IRB prior to implementation of any change(s).  The investigator is responsible for 
informing the IRB of the progress of the study and for obtaining annual IRB renewal.  The 
IRB must be informed by the investigator when the study is complete and should be provided 
with a summary of the results of the study as required by the IRB. 
3.0 
STUDY OBJECTIVES 
3.1 
Primary Objective 
To evaluate characteristics predictive of a baseline imaging study positive for M1 in patients 
with CRPC and no known M1. 
3.2 
Secondary Objectives 
• To characterize the sites of distant metastases by determining the proportion of patients 
with CRPC and no known M1 who receive a diagnosis of soft tissue and/or bone 
metastases at the time of the baseline imaging study. 
• To evaluate characteristics predictive of a future imaging study positive for M1 in 
patients with CRPC and no distant metastases (M0) at baseline. 
3.3 
Exploratory Objectives 
• To describe the percentage of patients with CRPC and undiagnosed M1 at baseline. 
• To explore biomarkers predictive of a baseline imaging study positive for M1. 
• To explore biomarkers predictive of a future imaging study positive for M1 in patients 
with M0 CRPC at baseline. 
• To evaluate characteristics predictive of a baseline imaging study positive for M1, as 
detected by different imaging modalities. 
• To evaluate characteristics predictive of a future imaging study positive for M1 in 
patients with M0 CRPC at baseline, as detected by different imaging modalities. 

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• To describe prostate cancer treatment practice patterns for patients with M0 CRPC. 
• To evaluate characteristics predictive of metastasis-free survival (MFS) in the population 
of patients with M0 CRPC. 
• For patients diagnosed with M1 CRPC: 
• To describe the timing and sequence of prostate cancer interventions. 
• To describe changes in serum PSA values, PSA progression, and PSA progression-
free survival. 
• To quantify OS from time of diagnosis with M1 CRPC. 
• To evaluate characteristics predictive of OS. 
4.0 
INVESTIGATIONAL PLAN 
This is a study to evaluate characteristics predictive of an imaging study positive for M1 in 
patients with CRPC.  The study will include 2 phases (M0 Phase and M1 Phase) in which 
patients are characterized by the absence or presence, respectively, of M1.  The study design 
is illustrated in Figure 1. 
 
 

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Figure 1: 
Study Design 
 
a
 
Every 6 months, starting from date of the patient’s registration, until 3 years after the last patient is 
registered: ECOG performance status; current opioid analgesic use (yes/no); pain status; prostate cancer 
interventions; survival status; imaging studies (if needed); clinical laboratory tests, including serum PSA values; 
safety events; and biomarkers (AOR); all such data that have become available since the previous visit will also 
be collected. 
b
 
Every 6 months until 5 years after the last patient is registered: ECOG performance status; new sites of 
metastases; current opioid analgesic use (yes/no); prostate cancer interventions; survival status; clinical 
laboratory results, including serum PSA; and safety events; all such data available since previous time point for 
data collection will be collected. 
Baseline 
The patient population consists of patients with CRPC and no known M1.  The patient will 
XQGHUJRWKHEDVHOLQHYLVLW 28 days after written informed consent is obtained.  Baseline 
assessments will include demographics and medical history; date of diagnosis with CRPC, 
with confirming serum PSA values and associated hormonal therapy; prostate cancer imaging 
study history; Eastern Cooperative Oncology Group (ECOG) performance status; height and 
weight; Adult Comorbidity Evaluation-27 (ACE-27); Gleason score; serum PSA history; 
current opioid analgesic use (yes/no); concomitant medications; pain status (with Brief Pain 
Inventory [BPI]); documentation of prior and ongoing prostate cancer interventions; and 
imaging studies (bone and soft tissue) to determine M1 disease status.  In addition, blood 
samples will be collected for clinical laboratory tests (alkaline phosphatase, hemoglobin, 

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lactate dehydrogenase [LDH], serum albumin, serum PSA, and testosterone), and for AOR, if 
patient provides consent, for biomarkers potentially predictive of treatment effects, or 
prognostic for MFS, OS, or an imaging study positive for metastatic disease.   
Patients who have undergone an imaging study to determine the presence of M1 (bone and/or 
soft tissue) ≤ 3 months prior to signing the ICF are ineligible.  However, these patients may 
enter the study > 3 months after their last imaging study if at that time they meet all eligibility 
criteria.  Patients who are deemed eligible on the basis of inclusion/exclusion criteria will be 
registered in the trial and receive a unique identifier at that time. 
Patients with baseline imaging studies confirming M0 CRPC will be entered into the M0 
Phase.  Patients with a baseline imaging study indicating previously unknown M1 CRPC will 
be entered into the M1 Phase. 
M0 Phase   
During the M0 Phase, there are 2 types of visits.  Post-baseline imaging studies are not 
required in the M0 Phase and are performed if the investigator determines imaging study(ies) 
is/are needed to assess development of metastases (M1 CRPC).  Depending on the timing of 
an imaging study, its results may be recorded as part of the 6-month M0 Phase study visit or 
part of an M0 Phase imaging visit, as described below: 
• 6-month M0 Phase study visit: A scheduled 6-month M0 Phase study visit (office visit), 
will occur every 6 months (± 1 month), starting from the date of the patient’s registration, 
until 3 years after the last patient is registered.  Any imaging study that occurs within 
1 month of a 6-month M0 Phase study visit will be considered part of that 6-month M0 
Phase study visit, and no repeat study assessments will be required. 
• M0 Phase imaging visit: This visit occurs if, outside of the 1-month window for the  
6-month M0 Phase study visit, the investigator determines imaging study(ies) is/are 
needed to assess development of metastases (M1 CRPC). 
The choice of imaging modality will depend on the study site’s standard of care; the same 
modality should be used for all images for a given patient until diagnosis of M1 CRPC.  
However, if the modality is changed to one with greater sensitivity (e.g., Tc 99m to NaF 
PET/CT or MRI) and diagnosis of M1 CRPC occurs at first use of a new imaging modality, 
an additional imaging study with the previous modality will be performed within 1 month 
after the positive imaging study; this additional imaging study will be reimbursed by the 
sponsor.  However, if the modality is changed to one with lower sensitivity, an imaging study 
with the previous higher modality will not be performed. 
Assessments for both types of M0 Phase visits include: ECOG performance status, current 
opioid analgesic use (yes/no), pain status (with BPI), prostate cancer interventions since the 
previous visit, survival status, blood samples for clinical laboratory tests (alkaline 

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phosphatase, hemoglobin, LDH, serum albumin, and serum PSA) and for AOR (if patient has 
consented to AOR), and safety events (serious adverse events [SAEs], see Safety Measures, 
below); all such data that have become available since the previous visit will also be 
collected.   
M1 Phase   
M1 Phase is observational.  Patients will enter M1 Phase when diagnosed with M1 CRPC at 
registration or at any M0 Phase study visit.  Patients identified with an imaging study positive 
for M1 disease anytime during the M0 Phase will enter M1 Phase and begin following the 
schedule of assessments for M1 Phase starting at the next 6-month visit.  For those patients 
who enter M1 Phase because of a positive imaging study during M0 Phase, an ACE-27 is 
required to be completed within 6 months after the patient’s last M0 Phase visit.   
During M1 Phase, data will be collected (via clinic visits, reviews of the patient’s medical 
record, and/or telephone calls) every 6 months (± 1 month) until 5 years after the last patient 
is registered.  At each 6-month time point during M1 phase, all data that have become 
available since the previous time point will be collected regarding ECOG performance status, 
new sites of metastases, current opioid analgesic use (yes/no), prostate cancer interventions, 
survival status, clinical laboratory (alkaline phosphatase, hemoglobin, LDH, serum albumin, 
and serum PSA) data, and safety events (SAEs, see Section 7.6.18). 
In interventional clinical trials, the Prostate Cancer Working Group currently recommends 
measurement of serum PSA levels every 3 or 4 weeks and CT or MRI every 12 weeks to 
assess disease progression (Scher 2008).  During M1 Phase, the sponsor anticipates patients 
will be monitored similarly.  The sponsor acknowledges that each M1 Phase patient will 
receive care appropriate for the treatment being administered and the standard of care in the 
investigator’s clinical practice.  At each 6-month time point for data collection during M1 
Phase, all prostate cancer interventions administered during the prior 6-month period, 
including indication(s) for choice of therapy, starting dose, timing (start and stop dates), and 
rationale for starting and stopping therapy (e.g., PSA progression), will be recorded on the 
electronic case report form (eCRF). 
The anticipated duration of the study is at least 7 years, including 2 years for accrual and up 
to 5 years for follow-up after the last patient is registered. 
The Schedule of Assessments is presented in Table 1. 
5.0 
STUDY POPULATION 
Men with CRPC and no known M1 disease who are at least 18 years of age at baseline are 
eligible.  A minimum of 2000 patients will be registered in this trial.  Patients must meet the 
following eligibility criteria to be registered in the study: 

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5.1 
Inclusion Criteria 
5.1.1. Written informed consent obtained prior to the initiation of study procedures. 
5.1.2. Men ≥18 years of age. 
5.1.3. Histologically documented prostatic adenocarcinoma confirmed by a pathology 
report from prostate biopsy or a RP specimen.  Patients whose pathology reports 
are no longer available may be enrolled if, in the opinion of the investigator, the 
patient has a clinical course consistent with prostatic adenocarcinoma. 
5.1.4. History of CRPC:  A sequence of 2 rising serum PSA values compared to the 
single lowest serum PSA value (nadir), measured at least 7 days apart where the 
second value is ≥ 2 ng/mL (Scher 2008), in the setting of surgical or continuous 
medical castration (defined as testosterone ≤ 50 ng/dL with either a luteinizing 
hormone-releasing hormone [LHRH] agonist or antagonist as monotherapy).  
Patients who subsequently receive combination and/or secondary hormonal 
treatments (e.g., combined androgen blockade [CAB]) that reduce or control 
serum PSA elevation are considered to have CRPC and are eligible. 
 
5.2 
Exclusion Criteria 
5.2.1. Known M1 disease:  Previous imaging studies have been positive for bone or 
visceral metastases, or for lymph nodes having a measurable diameter ≥ 2 cm.  A 
prostate mass or recurrence solely in the prostate bed is not considered metastatic 
disease (Scher 2008). 
5.2.2. Undergone imaging study for metastatic prostate cancer ≤ 3 months prior to the 
date written informed consent is obtained.  Patients with previous imaging 
studies may enter this trial > 3 months after their last imaging study if at that time 
they meet all eligibility criteria. 
5.2.3. ECOG performance status ≥ 3. 
5.2.4. Known malignant pleural effusions or ascites. 
5.2.5. Current or prior treatment with investigational therapy for M0 CRPC, Taxotere 
(docetaxel), Provenge® (sipuleucel-T), Zytiga (abiraterone acetate), Xtandi 
(enzalutamide), Jevtana (cabazitaxel), or Xofigo (radium Ra 223 dichloride). 
5.2.6. Any medical intervention or other condition which, in the opinion of the 
Principal Investigator or the Medical Monitor, could compromise adherence with 
study requirements or otherwise compromise the study objectives. 
5.2.7. Treatment for or history of malignancy (stage I-IV) other than prostate cancer or 
non-melanoma skin cancer within ≤ 5 years. 
 

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5.3 
Removal of Patients from the Study 
Whenever possible, patients should remain in the study and continue with protocol-specified 
assessments.  A patient may be withdrawn from the study if, in the investigator's clinical 
judgment, it is in the best interests of the patient. 
Patients may discontinue their participation in the study at any time without prejudice toward 
their future medical care.  A patient may choose to discontinue all evaluations and 
participation (including survival follow-up), or may discontinue all study evaluations with the 
exception of being followed for survival.  If a patient chooses to withdraw from the study, the 
investigator should make every reasonable attempt to confirm the status of all ongoing SAEs 
meeting the criteria defined in Section 7.6.18.  The date and reason for withdrawal will be 
recorded in the source documentation and on the eCRF. 
If a patient fails to respond to requests for follow-up, the study site will (at a minimum) send 
a registered letter to the patient requesting contact.  All attempts to resume contact (including 
copies of written correspondence) will be included in the source documentation.  Patients 
who do not respond to requests for follow-up after all reasonable attempts to establish contact 
will be considered lost to follow-up.  Data on all patients who withdraw consent or are 
determined to be lost to follow-up will be reviewed by the investigator through the National 
Death Index (NDI) or Social Security Death Index (SSDI) to ascertain any deaths not 
reported in the study.  The date of death, when available, will be gathered from the NDI or 
SSDI and recorded on the eCRF. 
Any patient who is not diagnosed with M1 CRPC and receives at least 1 partial (> 0 mL) 
infusion of Provenge during the study will be withdrawn from the study.  Serious adverse 
events that occur in such patients will be recorded as described in Section 7.6.18. 
6.0 
TREATMENTS 
No treatments will be administered as part of this study. 
7.0 
STUDY ASSESSMENTS AND PROCEDURES 
Patients will provide written informed consent and those that are eligible on the basis of 
inclusion/exclusion criteria will be registered in the trial and receive a unique identifier at that 
time.   
The study assessments and procedures to be performed during the study are summarized in 
the Schedule of Assessments (Table 1) and described in Section 7.6. 
7.1 
Baseline Visit 
The baseline visit will occur ≤ 28 days after written informed consent is obtained and include 
the following: 

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• Demographics and medical history, including prior and current medical conditions or 
illness, and allergies to medications. 
• Date of diagnosis with CRPC, with confirming serum PSA values and associated 
hormonal therapy. 
• Confirmation of no current or prior treatment with investigational therapy for M0 
CRPC, Taxotere (docetaxel), Provenge® (sipuleucel-T), Zytiga (abiraterone acetate), 
Xtandi (enzalutamide), Jevtana (cabazitaxel), or Xofigo (radium Ra 223 dichloride). 
• Prostate cancer imaging study history.   
• Confirmation that no imaging study to determine the presence of bone or soft tissue 
metastases was performed ≤ 3 months prior to the date written informed consent was 
obtained. 
• ECOG performance status. 
• Height and weight. 
• ACE-27. 
• Gleason score. 
• Serum PSA history. 
• Current opioid analgesic use (yes/no). 
• Concomitant medications (prescription medications only). 
• Pain status (with BPI). 
• Previous and ongoing prostate cancer interventions.  Prostate cancer interventions 
include but are not limited to radiation, chemotherapy, hormonal therapy, 
investigational cancer therapies, all other systemic therapies (including steroids), and 
surgery for prostate cancer.  Record indication(s) for choice of therapy, starting dose, 
timing (start and stop dates), and rationale for starting and stopping therapy (e.g., 
PSA progression) on the eCRF. 
• Bone and soft tissue imaging studies for detection of metastatic prostate cancer. 
• Blood sample for clinical laboratory tests at local laboratory, as indicated in the 
Schedule of Assessments (Table 1). 
• Blood sample for biomarker analysis, providing the patient has consented to AOR. 
 
7.2 
Registration 
Registration occurs after the inclusion and exclusion criteria have been confirmed. 

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7.3 
Scheduled 6-Month M0 Phase Study Visit 
For patients in the M0 Phase, scheduled visits will occur every 6 months (± 1 month), starting 
6 months from the date of the patient’s registration, and will continue until 3 years after the 
last patient is registered.  All data that have become available since the previous visit 
regarding the parameters listed below will be collected.  Imaging studies are optional and will 
be determined by investigator assessment of need.  Any imaging study that occurs within 1 
month of a 6-month M0 Phase study visit will be considered part of that 6-month M0 Phase 
study visit, and no repeat assessments will be required.   
The following will occur at each scheduled 6-month M0 Phase study visit: 
• ECOG performance status. 
• Current opioid analgesic use (yes/no). 
• Pain status (with BPI). 
• Prostate cancer interventions as described in Section 7.6.13. 
• Survival status.  The terms “alive” with the date of confirmation, “deceased”, or 
“unconfirmed” are collected.  For those patients recorded as “deceased”, an 
additional eCRF page entitled “Date and Cause of Death” will become available.  On 
this page, “Date of death” and “Cause of Death (check all that apply): Disease 
progression, Cardiac event, New primary cancer, Cerebrovascular event, and other 
(specify)”, are listed as choices. 
• Bone and soft tissue imaging studies for detection of metastatic prostate cancer (optional). 
• Blood sample for clinical laboratory tests at local laboratory, as indicated in the 
Schedule of Assessments (Table 1). 
• Serious adverse events in patients who receive at least 1 partial (> 0 mL) infusion of 
Provenge that occur ≤ 30 days after the last infusion, regardless of relationship to 
Provenge;  
• Blood sample for biomarker analysis, providing the patient has consented to AOR.  
This sample is collected within ± 1 month of an imaging study if it occurs during the 
± 1 month visit window. 
7.4 
M0 Phase Imaging Visits  
This visit occurs if the investigator determines that imaging study(ies) is/are needed to assess 
development of metastatic disease (M1 CRPC) and the imaging occurs > 1 month after 
baseline or more than 1 month before or after a 6-month M0 Phase study visit.  The following 
will occur during the visit: 
• ECOG performance status. 
• Current opioid analgesic use (yes/no). 

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• Pain status (with BPI). 
• Prostate cancer interventions as described in Section 7.6.13 
• Survival status as described in Section 7.6.14. 
• Bone and soft tissue imaging studies for detection of metastatic prostate cancer. 
• Blood sample for clinical laboratory tests at local laboratory, as indicated in the Schedule 
of Assessments (Table 1). 
• Serious adverse events in patients who receive at least 1 partial (> 0 mL) infusion of 
Provenge that occur ≤ 30 days after the last infusion, regardless of relationship to 
Provenge. 
• Blood sample for biomarker analysis (within ± 1 month of imaging), providing the patient 
has consented to AOR. 
 
Any imaging study that occurs within 1 month of a 6-month M0 Phase study visit will be 
considered part of that 6-month M0 Phase study visit, and no repeat assessments will be 
required. 
7.5 
M1 Phase Data Collection 
The M1 Phase will be observational.  For patients in M1 Phase, data will be collected every  
6 months (± 1 month) until 5 years after the last patient is registered. 
At each 6-month time point during M1 Phase, all data that have become available since the 
previous time point  regarding the parameters listed below will be collected.  For patients 
who enter M1 Phase because of an M0 Phase study visit that includes an imaging study 
positive for M1, all such data that have become available since the last scheduled 6-month 
M0 Phase study visit will be collected. 
The data to be collected during M1 Phase include: 
• ECOG performance status. 
• New sites of metastases. 
• ACE-27 assessment (for those patients who enter M1 Phase because of an M0 Phase 
study visit that includes an imaging study positive for M1, an ACE-27 is required to be 
completed within 6 months after the patient’s last M0 phase study visit).   
• Current opioid analgesic use (yes/no). 
• Prostate cancer interventions as described in Section 7.6.13. 
• Survival status as described in Section 7.6.14. 

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• Clinical laboratory results (alkaline phosphatase, hemoglobin, LDH, serum albumin, and 
serum PSA). 
• Serious adverse events in patients who receive at least 1 partial (> 0 mL) infusion of 
Provenge that occur ≤30 days after the last infusion, regardless of relationship to 
Provenge. 
Data collection during M1 Phase may occur by clinic visits, reviews of the patient’s medical 
record, or telephone calls, with the call documented in the patient’s medical record.  Clinic 
visits or telephone calls may occur by the following methods: 
• Patient visit at the study site. 
• Telephone call from the study site to the patient’s physician. 
• Telephone call between the study site and the patient. 
 
 
 

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Table 1: 
Schedule of Assessments—M0/M1 Phases 
Event 
Baseline 
M0 Phase 
M1 Phase 
Timing 
≤ 28 days after 
informed  
consent 
obtained 
From date of registration  
until 3 years after  
last patient is registered 
From date of 
registration until 5 
years after last 
patient is registered 
6-month M0 
Phase study visit 
(± 1 month) 
M0 Phase 
imaging visit as 
needed 
(> 1 month after 
previous study 
visit) 
Data collection  
every 6 months  
(± 1 month) 
Clinical evaluations 
 
 
 
 
Demographics and medical history 
X 
 
 
 
Date of diagnosis with CRPC, with 
confirming serum PSA values and 
associated hormonal therapy 
X 
 
 
 
Prostate cancer imaging study history 
Xab 
 
 
 
ECOG performance status 
X 
X 
X 
X 
New sites of metastases 
 
X 
X 
X 
Height and weight 
X 
 
 
 
Registration 
Xc 
 
 
 
Prognostic factors and other 
evaluations 
 
 
 
 
ACE-27 
X 
 
 
Xd 
Gleason score 
X 
 
 
 
Serum PSA historye 
X 
 
 
 
Current opioid analgesic use (yes/no) 
X 
X 
X 
X 
Concomitant medications 
X 
 
 
 
Pain status with Brief Pain Inventory 
X 
X 
X 
 
Prostate cancer interventionsf 
X 
X 
X 
X 
Survival status 
 
X 
X 
X 
Imaging studies (bone and soft tissue)g 
X 
Optionalh 
X 
 
Clinical laboratory tests 
 
 
 
 
Alkaline phosphatase, hemoglobin, 
LDH, serum albumin 
X 
X 
X 
Xi 
Serum PSA 
X 
X 
X 
Xi 
Testosterone 
X 
 
 
 
Safety Eventsj 
 
X 
X 
X 
AOR 
X 
X 
X 
 
Abbreviations:  ACE-27=Adult Comorbidity Evaluation-27; AOR=additional optional research (for biomarkers); 
CRPC=castration-resistant prostate cancer; ECOG=Eastern Cooperative Oncology Group; eCRF=electronic case report 
form; LDH=lactate dehydrogenase; M0=no distant metastases; M1=distant metastases; PSA=prostate-specific antigen; 
SAE=serious adverse event. 
 
 
 
 
 
 
 

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a 
Patients who have undergone an imaging study to determine the presence of M1 (bone and/or soft tissue) ≤3 months 
prior to signing the informed consent form are not eligible. 
b 
Record prostate cancer imaging studies completed from the time of biochemical recurrence after primary therapy until 
the baseline visit. 
c 
Registration occurs after the inclusion and exclusion criteria have been confirmed 
d 
For those patients who enter M1 Phase because of a positive imaging study at a 6-month M0 Phase study visit or an M0 
Phase imaging visit, clinic staff will complete the ACE-27 within 6 months after the patient’s most recent M0 Phase 
study visit and not at other time points. 
e 
All serum PSA values from the date of diagnosis with CRPC until the date of written informed consent, where 
available, will be recorded on the eCRF. 
f 
Prostate cancer interventions include but are not limited to radiation, chemotherapy, hormonal therapy, investigational 
cancer therapies, all other systemic therapies (including steroids), and surgery for prostate cancer.  Record indication(s) 
for choice of therapy, starting dose, timing (start and stop dates), and rationale for starting and stopping therapy on the 
eCRF. 
g 
The number and sites of bone, regional or distant nodal or visceral metastases, if present, will be recorded on the eCRF.  
Choice of imaging modality depends on study site’s standard of care; the same modality should be used for all images 
for a given patient until diagnosis of M1 CRPC.  However, if modality is changed and diagnosis of M1 CRPC occurs 
during first use of a new imaging modality, an additional imaging study with the previous modality will be performed 
within 1 month of the positive imaging study; this additional imaging study will be reimbursed by the sponsor.  
However, if the change is from a higher to a lower sensitivity modality, the higher sensitivity modality will not be 
repeated. 
h 
Frequency of imaging studies will be at investigator’s assessment of need.  Imaging studies performed within 1 month 
of a 6-month M0 Phase study visit will be considered part of that visit. 
i 
For patients in M1 Phase, clinical laboratory results, including serum PSA data, that have become available since the 
previous time point for data collection will be recorded on the eCRF. 
j 
For patients who receive at least 1 partial (>0 mL) infusion of Provenge, record SAEs that occur ≤ 30 days after the last 
infusion, regardless of relationship to Provenge. 
 
 
 
 

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7.6 
Procedures and Assessments 
7.6.1 
Demographics and Medical History  
The following demographic data will be recorded on the eCRF for all patients: date of birth, 
ethnicity, and race.   
The following medical history information will be recorded on the eCRF at the baseline visit: 
historic and current medical conditions or illness, allergies to medications, and prior prostate 
cancer interventions, including therapies and surgical procedures. 
7.6.2 
Date of Diagnosis with CRPC 
The date of diagnosis with CRPC will be confirmed at the baseline visit.  A sequence of 2 
rising serum PSA values (compared to a nadir value) measured at least 7 days apart where the 
second value is ≥ 2 ng/mL (Scher 2008), in the setting of surgical or continuous medical 
castration (defined as testosterone ≤ 50 ng/dL with either an LHRH agonist or antagonist as 
monotherapy) is required.  Patients who subsequently receive combination and/or secondary 
hormonal treatments (e.g., CAB) that reduce or control their serum PSA elevation are 
considered to have CRPC and are eligible for the study. 
The date of diagnosis with CRPC is defined as the date of the first serum PSA value above 
nadir in the sequence of serum PSA values used to confirm the presence of CRPC.  The date 
of diagnosis with CRPC will be recorded on the eCRF. 
7.6.3 
Prostate Cancer Imaging Study History 
At the baseline visit, all previous imaging studies for prostate cancer (type and date) that were 
completed from the time of biochemical recurrence after primary curative therapy until the 
baseline visit will be recorded on the eCRF.  For patients who have not received primary 
curative therapy, all imaging studies completed from the time of diagnosis until the baseline 
visit will be recorded on the eCRF. 
Biochemical recurrence is defined as a rising serum PSA after primary curative therapy as 
follows: 
• If primary therapy was RP (with or without external beam radiation therapy), rising serum 
PSA is defined as 2 consecutive rising values above 0.2 ng/mL, each taken ≥ 3 weeks 
apart, and the last value is ≥ 0.5 ng/mL. 
• If primary therapy was external beam radiation, rising serum PSA is defined per the 
Phoenix definition (Roach 2006), i.e., as 2 consecutive rising values, each taken ≥ 3 
weeks apart and above the serum PSA nadir plus 2.0 ng/mL. 
 

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7.6.4 
Eastern Cooperative Oncology Group Performance Status 
ECOG performance status (Appendix 1) will be collected and recorded on the eCRF at the 
baseline visit, scheduled 6-month M0 Phase study visits, M0 Phase imaging visits, and time 
points for data collection in M1 Phase. 
7.6.5 
New Sites of Metastases  
At all M1 data collection time points, new sites of visceral, nodal or bone metastases will be 
recorded on the eCRF. 
7.6.6 
Height and Weight 
Height and weight will be measured at the baseline visit and recorded on the eCRF. 
7.6.7 
Adult Comorbidity Evaluation 
The ACE-27 (Appendix 2) is used to identify the important medical comorbidities and 
determine the overall comorbidity score.  For all patients, clinic staff will complete the 
ACE-27 at the baseline visit.  For those patients who enter M1 Phase because of a positive 
imaging study during M0 Phase, an ACE-27 is required to be completed within 6 months 
after the patient’s last M0 Phase visit. 
7.6.8 
Gleason Score 
At the baseline visit, Gleason scores from initial prostate cancer diagnosis and, if available, 
following grade change after RP, will be collected and recorded on the eCRF.  The highest 
and second highest values will be recorded. 
7.6.9 
Prostate-specific Antigen History 
At the baseline visit, all serum PSA values, as available, from the date of diagnosis with 
CRPC as defined in the protocol until the date written informed consent is obtained will be 
recorded on the eCRF.  Serum PSA values documented in a medical record are acceptable. 
7.6.10 
Current Opioid Analgesic Use 
At the baseline visit and all M0 and M1 data collection, current opioid use (yes/no) will be 
recorded on the eCRF. 
7.6.11 
Concomitant Medications 
At the baseline visit, the patient’s current prescription medications and indications will be 
recorded on the eCRF.  Only prescription medications will be recorded. 

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7.6.12 
Pain Status 
At the baseline visit, scheduled 6-month M0 Phase study visits and M0 Phase imaging visits, 
pain status will be measured with the BPI (Appendix 3) and the information will be recorded 
on the eCRF. 
7.6.13 
Prostate Cancer Interventions 
At the baseline visit, all previous and ongoing prostate cancer interventions will be recorded.  
From registration until the patient is discontinued from or completes the study, all prostate 
cancer interventions will be recorded on the eCRF.  Prostate cancer interventions include but 
are not limited to radiation, chemotherapy, hormonal therapy, investigational cancer 
therapies, all other systemic therapies (including steroids), and surgery for prostate cancer.  
Information collected regarding prostate cancer interventions will include the indication(s) 
for choice of therapy, starting dose, timing (start and stop dates), and rationale for starting 
and stopping therapy (e.g., PSA progression). 
7.6.14 
Survival Status 
Survival status is assessed in patients at all M0 and M1 data collection time points.  The 
terms “alive” with the date of confirmation, “deceased”, or “unconfirmed” are collected.  For 
those patients recorded as “deceased”, an additional eCRF page entitled “Date and Cause of 
Death” will become available.  On this page, “Date of death” and “Cause of Death (check all 
that apply): Disease progression, Cardiac event, New primary cancer, Cerebrovascular event, 
and other (specify)”, are listed as choices. 
7.6.15 
Imaging Studies 
Patients will undergo bone imaging studies (e.g., MRI, 99mTc bone scintigraphy or 18F‐NaF 
PET/CT) and soft tissue imaging studies (e.g., contrast-enhanced abdominal and pelvic CT or 
MRI) at the baseline visit and M0 Phase visits in order to detect any M1 disease.  The 
imaging modality will be determined based on the study site’s standard of care and will be 
recorded on the eCRF. 
The presence of M1 disease will be determined by the presence of bone, regional or distant 
nodal, or visceral metastasis, as follows: 
• Bone metastasis 
Patients with one or more unequivocal bone lesions as identified by site's standard for 
imaging modality will be considered to have M1 CRPC.  Patients with equivocal scans 
determined by standard imaging (e.g., 99mTc bone scan) will be evaluated by more 
sensitive imaging modalities such as CT, 18F-NaF PET/CT, or MRI within 1 month of the 
equivocal scan to confirm M1 disease status (Adams 2011). 

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• Regional or distant nodal metastasis 
Patients diagnosed with lymph node(s) (measuring ≥ 2 cm on the greatest diameter) in 
either regional pelvic or distant lymph nodes will be considered to have M1 disease 
(Scher 2008). 
Examples of regional lymph nodes include:  hypogastric, obturator, internal and external 
iliac and lateral, presacral and promontory sacral lymph nodes (Adams 2011). 
Examples of distant lymph nodes, which lie above the bifurcation of the common iliac 
arteries and outside of the confines of the true pelvis, include: aortic, common iliac, deep 
inguinal, superficial inguinal, supraclavicular, cervical, scalene, and retroperitoneal 
lymph nodes (Adams 2011). 
• Visceral metastasis 
Patients diagnosed with metastasis to liver, lung, brain, or other solid organ will be 
considered to have M1 disease. 
The number and sites of bone, regional or distant nodal, or visceral metastases, if present, 
will be recorded on the eCRF. 
The same bone and soft tissue imaging modalities utilized at baseline should be used for all 
images for a given patient until diagnosis of M1 CRPC.  However, the imaging modality may 
be changed at the investigator’s discretion, assuming that subsequent imaging studies are 
performed with the new modality.  If the diagnosis of M1 CRPC occurs during the first use of 
a new imaging modality (e.g., first use of 18F‐NaF PET/CT imaging after previous use of 
99mTc bone scintigraphy), an additional imaging study with the previous imaging modality 
will be performed within 1 month after the positive imaging study to allow comparison of the 
sensitivity and specificity of the 2 methods; this additional imaging study will be reimbursed 
by the sponsor.  However, if the change is from a higher to a lower sensitivity modality, the 
higher sensitivity modality will not be repeated. 
7.6.16 
Clinical Laboratory Tests 
Blood samples for assessment of the following parameters will be obtained at the baseline 
visit and all M0 Phase visits unless otherwise noted: 
• Alkaline phosphatase 
• Hemoglobin 
• Lactate dehydrogenase (LDH) 
• Serum albumin 
• Serum PSA 
• Testosterone (baseline visit only) 

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Local laboratories will be used for the above laboratory tests and the results will be recorded 
on the eCRF.   
At each time point for data collection during M0 phase and M1 phase, clinical laboratory 
(alkaline phosphatase, hemoglobin, LDH, serum albumin) and  serum PSA data that have 
become available since the previous time point will be recorded in the eCRF.  Blood samples 
for clinical laboratory or serum PSA values will not be collected during M1 Phase. 
7.6.17 
Additional Optional Research for Biomarkers 
Patients will be given the opportunity to consent to allow Dendreon to collect investigational 
blood samples for use in AOR, which will include biomarker analysis and other additional 
testing.  The samples will be analyzed for biomarkers that may be predictive of treatment 
effects and/or prognostic for MFS, OS, or an imaging study positive for metastatic disease.  
The samples will be retained for an indefinite period of time.  They may be used for gene and 
gene expression analysis, and retained samples may be sent to outside laboratories for testing.  
Retained samples will be used for research only, and will not be sold.  AOR blood samples 
will not be identified using patient names or other personal identifiers.  Neither the patient 
nor the study site will receive AOR testing results. 
For patients who provide consent for AOR, a whole blood sample will be obtained at the 
baseline visit   and each M0 Phase visit (at scheduled 6-month M0 Phase study visits and M0 
Phase imaging visits [within ± 1 month]) until diagnosis with M1 CRPC, or the M0 Phase 
patient completes or is discontinued from the study.  Such samples will not be collected from 
patients who do not provide additional consent for AOR. 
7.6.18 
Serious Adverse Events 
The collection of adverse events (AEs) will be limited to SAEs in patients who receive at 
least 1 partial (> 0 mL) infusion of Provenge during the study and that occur at any time from 
the first infusion through 30 days after the last infusion, regardless of relationship to 
Provenge. 
Any patient who is not diagnosed with M1 CRPC and receives at least 1 partial (> 0 mL) 
infusion  of Provenge during the study will be withdrawn from the study.  Serious adverse 
events that occur in such patients will be recorded as described above. 
Definition of a Serious Adverse Event 
An SAE is defined as any adverse drug experience occurring at any dose that results in any of 
the following outcomes:  death, a life-threatening adverse drug experience, inpatient 
hospitalization or prolongation of existing hospitalization, a persistent or significant 
disability/incapacity, or a congenital anomaly/birth defect.  Important medical events that 
may not result in death, be life-threatening, or require hospitalization may be considered 

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SAEs when, based upon appropriate medical judgment, they may jeopardize the patient and 
may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition.  Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that 
do not result in inpatient hospitalization, or the development of drug dependency or drug 
abuse. 
Categories for Ranking the Relationship of a Serious Adverse Event 
None: 
The SAE is clearly related to other factors, such as the patient’s 
clinical state, environmental factors, or other modes of therapy or 
concomitant drugs administered to the patient. 
Possible: 
The SAE follows a reasonable temporal sequence from a study-
required procedure or administration of Provenge, but could 
readily have been produced by the patient’s clinical state, 
environmental factors, or other modes of therapy or concomitant 
drugs administered to the patient. 
Probable: 
The SAE follows a reasonable temporal sequence from a study-
required procedure or administration of Provenge and cannot 
readily have been produced by the patient’s clinical state, 
environmental factors, or other modes of therapy or concomitant 
drugs administered to the patient. 
Reporting Requirements for a Serious Adverse Event 
Serious adverse events that meet the criteria for collection during the study, as outlined in this 
section, will be reported to Dendreon or designee.  Serious adverse events must be reported to 
Dendreon or designee within 24 hours of first knowledge of the event by completing the SAE 
form.  The SAE information must be reported to Dendreon or designee within 24 hours by 
telephone or facsimile, and a completed written report using Dendreon’s SAE Report Form 
must be submitted by facsimile within 3 business days to: 
 
Dendreon Corporation 
 
Attn:  Safety Manager 
 
Facsimile:  (877) 630-5352 
 
Telephone:  (800) 349-8086 
 
Email:  DendreonSafety@unitedbiosource.com 
 
Telephone (24-hour access):  (877) 336-3736 
Significant new information regarding an ongoing SAE and the resolution must be sent to 
Dendreon or designee within 3 business days of awareness of the new information on the 
SAE Report Form. 

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Expedited Reporting Requirements 
Dendreon will notify the FDA or other applicable regulatory agencies and health authorities 
of any SAE in this study associated with the use of Provenge that is unexpected and at least 
possibly related.  Such notification will be provided within 15 calendar days after Dendreon’s 
initial receipt of the information for all SAEs. 
8.0 
STATISTICAL METHODS 
8.1 
Sample Size Considerations 
This study will identify patient characteristics at the time of the baseline imaging study that 
are predictive of an imaging study positive for M1 in patients with CRPC and no known M1.  
A minimum of 2000 patients will be registered in this study.  This sample size is based on the 
following considerations. 
The primary endpoint for the study will be the occurrence of a positive imaging study for M1 
at baseline (yes or no), a binary variable.  All patients with a baseline imaging study will be 
included in the analysis of the primary endpoint.  Yu et al (2012) found that 32% of 2577 
men screened for a trial enrolling patients with CRPC thought to be M0 did, in fact, have M1 
CRPC, and it is anticipated that this study will have a similar finding.  With 1000 patients at 
each of the 2 possible levels of a binary variable, for a total of 2000 patients, the variable is 
detectable with an odds ratio of 1.312 with 80% power using a 2-sided test at alpha = 0.05, 
assuming an imaging study positive for M1 at baseline in 34.95% and 29.05% of patients in 
level 1 and level 2 of the binary variable, respectively.  However, a binary variable that is 
distributed at a ratio of 1:5 at baseline would allow for an odds ratio of 1.422 to be detected 
with 80% power assuming an imaging study positive for M1 at baseline in 38.5% and 30.6% 
of the patients in level 1 and level 2 of the binary variable, respectively.   
8.2 
General Considerations 
8.2.1 
Analysis Populations 
The all-enrolled population will include all patients registered in the study.  The primary 
analysis will be based on the primary analysis population, which will include patients in the 
all-enrolled population who undergo a baseline imaging study.  In addition, patients with M0 
or M1 CRPC at baseline (M0 or M1 populations, respectively) will form separate analysis 
populations to address different questions of interest. 
8.2.2 
Interim Analysis 
No formal interim analysis is planned for this study.  Periodic summarization of the data will 
be performed on an ongoing basis.  However, as there are no formal hypotheses being tested 
in this protocol, no significance-level adjustments will be made for statistical testing or 
estimation procedures that may be utilized. 

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8.2.3 
Control Groups 
There is no reference product in this protocol.  Descriptive comparisons may be made to 
external datasets. 
8.3 
Analysis of Endpoints 
8.3.1 
Primary Endpoint 
The primary endpoint for the study will be the occurrence of an imaging study at baseline that 
is positive for M1 (yes or no) among all patients enrolled with a baseline imaging study.  
Logistic regression analyses will be used to analyze the primary endpoint.  Univariate logistic 
regression analyses will be performed separately for each variable of interest.  A multivariate 
logistic regression analysis will be performed including all variables of interest.  A stepwise 
regression model selection procedure will be used to identify a model that includes 
explanatory factors that are independently predictive of the occurrence of a positive imaging 
study.  The logistic regression model will be used to develop a formula for predicting the 
probability of a positive imaging study given specific values for the variables included in the 
final model. 
Variables that will be considered for inclusion in the model are age, race, ethnicity, duration 
of disease in years from initial diagnosis to study registration, total Gleason score at 
diagnosis, post-RP Gleason score total, baseline ECOG performance status, baseline 
hemoglobin, baseline alkaline phosphatase, baseline LDH, baseline serum albumin, baseline 
testosterone, baseline serum PSA, baseline PSADT, first serum PSA demonstrating CRPC, 
baseline body mass index (BMI), prior systemic therapy (yes or no), prior ADT (yes or no), 
prior RP (yes or no), and prior orchiectomy (yes or no), current opioid analgesic use (yes/no), 
and number of prior scans.  Baseline BPI scores, including worst pain in last 24 hours, least 
pain in last 24 hours, average pain in last 24 hours, and pain right now, will also be 
considered for inclusion. 
The above list of variables will be considered for inclusion in the final model; however, each 
variable will be initially screened and will be dropped from consideration for inclusion in the 
final model if it is shown to have little predictive value as a univariate predictor.  Candidate 
variables for the final model will be determined by the following algorithm.  A univariate 
logistic regression will be applied for each individual variable and all variables with p < 0.25 
will be considered as candidate variables for the final model.  Interaction terms will also be 
considered for the final model.  Interaction terms will be considered as candidates for the 
final model if the p-value for the interaction term is less than 0.25 from a model with 
predictor variables of variable a, variable b, and interaction of variable a and b.  Only 
variables with p < 0.25 from the univariate model screening procedure as discussed above 
will be considered for determining the list of interaction terms for consideration in the final 
model. 

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All candidate variables, including interaction terms identified by the algorithm discussed 
above, will be entered into the stepwise model selection procedure.  The criteria for a variable 
to enter the model will be p < 0.05 and variables will be retained in the model during the 
elimination step if p < 0.10.  The final model will include all terms identified from the 
stepwise selection procedure and will also include all main effect terms for any interaction 
variables identified in the stepwise model selection procedure. 
Although the above list of variables for consideration for inclusion in the model is a 
comprehensive one, addition or deletion of variables for consideration may occur.  Therefore, 
the complete list of candidate variables for inclusion in the model will be provided in the final 
statistical analysis plan. 
8.3.2 
Secondary Endpoints 
The proportion of patients who receive a diagnosis of M1 CRPC at the time of the baseline 
imaging study will be categorized as metastatic due to soft tissue (nodal and/or visceral) 
metastases, bone metastases, or both.  The percentage of patients in each category will be 
computed based on the primary analysis population. 
Logistic regression analyses, similar to the analyses described for the primary endpoint, will 
be used to identify characteristics predictive of an imaging study positive for M1 in the M0 
population.  Analyses will be performed using baseline information only as predictor 
variables with the outcome variable as a positive imaging study (yes/no) at any post-baseline 
time point.  In addition, an analysis will be performed on the M0 population using all imaging 
studies collected in the study as the outcome variable (positive=yes/negative=no) with 
predictor variables associated with each imaging study.  Appropriate methods accounting for 
the correlation of multiple studies for a patient, such as generalized estimating equations, will 
be used for this analysis.  Cox regression analyses incorporating information on the time to 
occurrence of a positive imaging study will be performed to supplement these analyses. 
8.3.3 
Exploratory Endpoints 
Prostate cancer treatment practice patterns will be summarized descriptively for patients with 
M0 CRPC and M1 CRPC.  Prostate cancer interventions prior to study entry will be 
summarized.  Additionally, the timing and sequence of prostate cancer interventions during 
the study will be summarized. 
The identification of biomarkers in the M0 population that are predictive of an imaging study 
positive for M1 will be performed using logistic regression and Cox regression, as previously 
described.  These analyses will be performed for both the primary endpoint (a positive 
imaging study at baseline) and the endpoint of a positive imaging study at any post-baseline 
time point. 

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The percentage of patients with CRPC with previously undiagnosed M1 at baseline will be 
calculated as 100 times the number of patients in the M1 analysis population divided by the 
total number of patients in the study. 
Logistic regression analyses will be used to determine patient characteristics in the M0 
population that are predictive of a positive imaging study at baseline as detected with 
different imaging modalities.  The differing imaging modalities include MRI, 99mTc bone 
scintigraphy, or 18F‐NaF PET/CT for bone imaging; and contrast-enhanced abdominal and 
pelvic CT or MRI for soft tissue imaging.  For each imaging modality, multivariate logistic 
regression modeling will be used to identify factors that are independently predictive of a 
positive imaging study.  These analyses will be performed for both the primary endpoint (a 
positive imaging study at baseline) and for the endpoint of a positive imaging study at any 
post-baseline time point. 
Metastasis-free survival will be defined as time from the date of the baseline imaging study to 
the first occurrence of M1 or death due to any cause in the M0 population.  Patients who are 
not observed to develop M1 or who do not die will be censored at the last time observed for 
determination of M1.  Only patients who are confirmed with M0 CRPC at study entry will be 
included in the analysis.  Cox regression analyses will be used to analyze the MFS endpoint.  
Univariate Cox regression analyses will be performed separately for each baseline variable of 
interest.  A multivariate Cox regression analysis will be performed including all baseline 
variables of interest.  Various model selection procedures will be investigated, including 
forward, backward, and stepwise regression to identify a model that includes explanatory 
factors that are independently predictive of development of M1 or death.  Supplementary 
analyses, including time-varying covariates of ECOG performance status and laboratory 
parameters, will also be provided. 
Overall survival will be defined as the time from diagnosis with M1 CRPC until death.  
Patients who do not die will be censored at the last date they were known to be alive.  
Analyses similar to those described for MFS will be performed in the M1 population to 
determine patient characteristics that can be used to predict OS.  The Kaplan-Meier method 
will be used to quantify the survival duration from the time of diagnosis with M1 CRPC.  In 
addition, the effect of prostate cancer interventions and their sequencing on OS will be 
evaluated using a Cox regression analysis with time-varying covariates. 
The timing and sequence of prostate cancer interventions will be summarized descriptively 
for the M1 population.  The time to prostate cancer interventions will be defined as the time 
from the date of diagnosis with M1 CRPC until initiation of the prostate cancer intervention. 
Changes in serum PSA levels during treatment for M1 CRPC will be summarized 
descriptively for the M1 population.  For treatments with sufficient patient numbers, changes 
in serum PSA levels over time, PSA progression, and PSA progression-free survival will be 

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summarized descriptively by treatment.  The maximum percentage reduction in serum PSA 
levels will also be summarized descriptively by treatment. 
8.4 
Safety Events 
In this study, the collection of AEs will be limited to SAEs and meeting the criteria defined in 
Section 7.6.18.  Serious adverse events will be summarized and listed by the Medical 
Dictionary for Regulatory Activities (MedDRA) preferred term within each system organ 
class.  Serious adverse events that occur multiple times for a patient will be counted only 
once per patient in incidence summary tables.  A listing of SAEs at least possibly related to 
Provenge will be provided. 
8.5 
Demographic and Baseline Characteristics 
Demographic information and baseline disease characteristics will be summarized.  Separate 
summaries will be provided for the primary analysis, M0, and M1 populations. 
8.6 
Patient Disposition 
The disposition of all patients screened and enrolled in the study will be summarized in 
aggregate.  Reasons for screening failure and premature study discontinuation will be 
summarized. 
8.7 
Concomitant Medications 
Concomitant medications will be presented in data listings. 
9.0 
REGULATORY REQUIREMENTS 
9.1 
Pre-Study Documentation 
Dendreon must receive the following documentation prior to initiation of the study: 
• Copy of signed Protocol Signature Page. 
• Copy of curriculum vitae of Principal Investigator, updated within the past 2 years. 
• Copy of current medical license for the Principal Investigator. 
• Copies of financial disclosure forms for all investigators. 
• Copy of the IRB approval letter for the study. 
• Documentation of the IRB approval of the ICF and copy of the IRB-approved ICF. 
• Copy of IRB-approved patient materials. 
• IRB membership list or Department of Human and Health Services Assurance 
Number. 
 

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9.2 
Investigator Obligations 
The Principal Investigator will be responsible for ensuring that all clinical study site 
personnel conduct the study in compliance with the Declaration of Helsinki and the ICH E6 
Guideline for GCP, including the archiving of essential documents.  The investigator will 
also ensure adherence to all national, state, and local laws of the pertinent regulatory 
authorities, including Federal regulations/guidelines set forth in 21 Code of Federal 
Regulations (CFR) §11, 50, 54, 56, and 312. 
The Principal Investigator will be responsible for the patient’s compliance to the study 
protocol, and may meet periodically with the Dendreon study monitor or Dendreon designee. 
All investigators must complete and return Financial Disclosure statements (including 
information on spouses, legal partners, or dependent children) before study initiation.  
Investigators must promptly update this information if any relevant changes occur in the 
course of the study or in the year after the study is completed (21CFR§54.4).  In addition, the 
Principal Investigator is responsible for providing Dendreon an adequate final report shortly 
after study participation is complete, in accordance with 21CFR§312.64. 
9.3 
Patient Confidentiality 
Individual patient medical information obtained as a result of this study is considered 
confidential and disclosure to third parties other than those noted below is prohibited.  
Patients’ individual identifying information will be kept as confidential as possible under 
local, state, and federal law.  Medical information may be given to the patient’s personal 
physician or to other appropriate medical personnel responsible for the patient’s welfare.  
Data generated as a result of this study are to be available for inspection on request by the 
FDA, Dendreon’s representative, or the IRB.  Dendreon may retain in its files copies of 
patient medical information required for auditing of eCRFs. 
Individual patient identities will not be disclosed in any report or publication related to the 
study, and will not be recorded on any eCRFs maintained by Dendreon. 
10.0 
PROTOCOL MANAGEMENT AND ADMINISTRATIVE CONSIDERATIONS 
10.1 
Study Documentation 
The investigator and study staff are responsible for maintaining a comprehensive and 
centralized filing system containing all study-related documentation.  These files must be 
suitable for inspection by Dendreon, representatives of Dendreon, or the FDA at any time, 
and should consist of the following elements: 
• Patient files, containing the completed eCRFs, supporting source documentation 
from the medical record including laboratory data, pathology reports, and the signed 
ICF. 

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• Regulatory files, containing the protocol with all amendments and protocol signature 
pages, copies of all other regulatory essential documentation, and all correspondence 
between the study site and the IRB and sponsor. 
Records are to be available for at least 2 years after study completion and the FDA is so 
notified. 
10.2 
Data Collection 
Data will be entered into the electronic data capture (EDC) system.  Trained study personnel 
will be responsible for entering data on the observations, tests, and assessments specified in 
the protocol into the EDC system and according to the eCRF Instructions.  The eCRF 
Instructions will also provide the study center with data entry instructions.  Data entered in 
the EDC system will be immediately saved to a central database and changes tracked to 
provide an audit trail. 
10.3 
Protocol Interpretation and Compliance 
To ensure accurate interpretation and implementation of the study, the procedures and 
endpoints defined in the protocol will be carefully reviewed by the investigator and his or her 
staff prior to the time of study initiation. 
10.4 
Study Monitoring 
A representative from Dendreon may visit each study site periodically to monitor adherence 
to the protocol, adherence to applicable FDA regulations, and the maintenance of adequate 
and accurate clinical records.  Electronic case report forms will be reviewed to ensure that 
key data are reported as specified by the protocol.  The Dendreon representative will be 
permitted to access patients’ complete medical records, laboratory data, and other source 
documentation as needed to appropriately monitor the study. 
10.5 
Quality Assurance 
The Dendreon Quality Assurance department may arrange to visit the investigator in order to 
audit the performance of the study at the study site and the study documents originating there.  
The audit may be conducted by a Dendreon representative or designee.  The investigator will 
be informed of the outcome of the audit. 
In addition, inspections by health authority representatives and/or the IRB may occur at any 
time.  The investigator must inform Dendreon Clinical Affairs or designee of any such 
inspection immediately.  Direct access to source documents and medical records will be 
required for audit and inspections. 

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10.6 
Disclosure of Data and Publication 
The investigator or others working on the study will submit all proposed publications, papers, 
abstracts or other written materials related to the study, or an outline of any proposed oral 
presentation with respect thereto, to Dendreon at least 1 month prior to (i) submission of such 
written materials for publication, or (ii) any proposed oral disclosure to a third party.  
Dendreon shall have the right to comment on such written material or outline; such comments 
shall be considered in good faith by the investigator in determining the final form of 
disclosure.  Notwithstanding any of the above, the investigator or others working on the study 
may not include any confidential information in any such publication or disclosure. 
 
 

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11.0 
REFERENCES 
Adams 2011 
Adams J and Cheng L, Lymph node-positive prostate cancer: 
current issues, emerging technology and impact on clinical 
outcome.  Expert Rev Anticancer Ther 2011;11(9):1457–1469. 
Brown 2010 
Brown JE, Sim S.  Evolving role of bone biomarkers in castration-
resistant prostate cancer.  Neoplasia 2010;12(9):685-696.  Review. 
Crawford 1989 
Crawford ED.  Combined androgen blockade.  Urology 1989;34(4 
Suppl):22-26; discussion 46-56.  Review. 
Even-Sapir 2006 
Even-Sapir E, Metser U, Mishani E, et al.  The detection of bone 
metastases in patients with high-risk prostate cancer: 99mTc-MDP 
planar bone scintigraphy, single- and multi-field-of-view SPECT, 
18F-fluoride PET, and 18F-Fluoride PET/CT.  J Nucl Med 
2006;47:287-297. 
Kane 2003 
Kane CJ, Amling CL, Johnstone PAS, et al.  Limited value of 
bone scintigraphy and computed tomography in assessing 
biochemical failure after radical prostatectomy.  Urology 
2003;61:607-611. 
Olmos 2012 
Olmos D, Brewer D, Clark J, et al.  Prognostic value of blood 
mRNA expression signatures in castration-resistant prostate 
cancer: a prospective, two-stage study.  Lancet Oncol 
2012;13(11):1114-1124.  doi: 10.1016/S1470-2045(12)70372-8.  
Epub 2012 Oct 9. 
Roach 2006 
Roach M 3rd, Hanks G, Thames H Jr, et al., Defining biochemical 
failure following radiotherapy with or without hormonal therapy 
in men with clinically localized prostate cancer: recommendations 
of the RTOG-ASTRO Phoenix Consensus Conference.  Int J 
Radiat Oncol Biol Phys 2006;65(4):965-974. 
Ross 2012 
Ross RW, Galsky MD, Scher HI, et al.  A whole-blood RNA 
transcript-based prognostic model in men with castration-resistant 
prostate cancer: a prospective study.  Lancet Oncol 
2012;13(11):1105-1113. 

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Schellhammer 1997 Schellhammer PF, Venner P, Haas GP, et al.  Prostate specific 
antigen decreases after withdrawal of antiandrogen therapy with 
bicalutamide or flutamide in patients receiving combined 
androgen blockade.  J Urol 1997;157(5):1731-1735. 
Scher 1993 
Scher HI, Kelly WK.  Flutamide withdrawal syndrome: its impact 
on clinical trials in hormone-refractory prostate cancer.  J Clin 
Oncol 1993;11(8):1566-1572. 
Scher 1996 
Scher HI, Zhang ZF, Nanus D, et al.  Hormone and antihormone 
withdrawal: implications for the management of androgen-
independent prostate cancer.  Urology 1996;47(1A Suppl):61-69. 
Scher 2008 
Scher HI, Halabi S, Tannock I, et al.  Design and end points of 
clinical trials for patients with progressive prostate cancer and 
castrate levels of testosterone: recommendations of the Prostate 
Cancer Clinical Trials Working Group.  J Clin Oncol 
2008;26(7):1148-1159. 
Siegel 2012 
Siegel R, DeSantis C, Virgo K, et al.  Cancer treatment and 
survivorship statistics, 2012.  CA Cancer J Clin 2012;62(4):220-
41.  doi: 10.3322/caac.21149.  Epub 2012 Jun 14.  Review.  
Erratum in: CA Cancer J Clin 2012;62(5):348. 
Small 1997 
Small EJ, Vogelzang NJ.  Second-line hormonal therapy for 
advanced prostate cancer: a shifting paradigm.  J Clin Oncol 
1997;15(1):382-388. 
Smith 2005 
Smith MR, Kabbinavar F, Saad F, et al.  Natural history of rising 
serum prostate-specific antigen in men with castrate nonmetastatic 
prostate cancer.  J Clin Oncol 2005;23(13):2918-2925. 
Ward 2005 
Ward JF, Moul JW.  Treating the biochemical recurrence of 
prostate cancer after definitive primary therapy.  Clin Prostate 
Cancer 2005;4(1):38-44. 
Yu 2012 
Yu EY, Miller K, Nelson J, et al.  Detection of previously 
unidentified metastatic disease as a leading cause of screening 
failure in a phase III trial of zibotentan versus placebo in patients 
with nonmetastatic, castration resistant prostate cancer.  J Urol 
2012;188(1):103-109.  doi: 10.1016/j.juro.2012.03.008.  Epub 
2012 May 12. 

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APPENDIX 1: 
ECOG PERFORMANCE STATUS CRITERIA 
ECOG Performance Status Scale 
Grade 
Description 
0 
Normal activity.  Fully active, able to carry on all pre-disease performance 
without restriction. 
1 
Symptoms, but ambulatory.  Restricted in physically strenuous activity, but 
ambulatory and able to carry out work of a light or sedentary nature (e.g., light 
housework, office work). 
2 
In bed <50% of the time.  Ambulatory and capable of all self-care, but unable to 
carry out any work activities.  Up and about more than 50% of waking hours. 
3 
In bed >50% of the time.  Capable of only limited self-care, confined to bed or 
chair more than 50% of waking hours. 
4 
100% bedridden.  Completely disabled.  Cannot carry on any self-care.  Totally 
confined to bed or chair. 
5 
Dead. 
 

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APPENDIX 2: 
ADULT COMORBIDITY EVALUATION-27 
 

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APPENDIX 3: 
BRIEF PAIN INVENTORY 
 

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P12-1 Statistical Analysis Plan was not finalized as there was insufficient data.