IMPRINT: A Pilot Study to Improve Germline Testing in At-Risk Patients With Prostate Cancer
Phase: NA
Conditions: Prostate Cancer
Sponsor: University of California, San Diego

A Pilot Study to Improve Germline Testing in At-Risk 
Patients with Prostate Cancer
NCT05470036
Document Date: 12/06/2021

Observational Study Protocol 
Study Code 
IMPRINT 
Version 
v3.0 
Date 
12/06/2021 
IMPRINT: A Pilot Study to Improve Germline Testing in At-Risk 
Patients with Prostate Cancer 
A quality improvement initiative to improve rates of germline testing among men 
with prostate cancer through the use of an in-clinic educational session.  
Sponsor: 
AstraZeneca 
Author: 
Rana R. McKay, MD 
Associate Professor 
University of California San Diego - Moores Cancer Center 
3855 Health Sciences Drive 
La Jolla, CA 92093 
City, State Zip code 
T: (858) 822-6185 
rmckay@health.ucsd.edu 

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TABLE OF CONTENTS 
PAGE 
 
TITLE PAGE ...................................... ERROR! BOOKMARK NOT DEFINED. 
TABLE OF CONTENTS ......................................................................................... 2 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ............................ 4 
RESPONSIBLE PARTIES ...................................................................................... 5 
PROTOCOL SYNOPSIS ......................................................................................... 6 
AMENDMENT HISTORY ..................................................................................... 8 
MILESTONES ......................................................................................................... 9 
1. 
BACKGROUND AND RATIONALE .................................................................. 10 
1.1 
Background ............................................................................................................ 10 
1.2 
Rationale ................................................................................................................ 13 
2. 
OBJECTIVES AND HYPOTHESES .................................................................... 14 
2.1 
Primary Objective(s) & Hypothesis(es) ................................................................. 14 
2.2 
Secondary Objective(s) & Hypothesis(es) (Optional) ........................................... 14 
2.3 
Exploratory Objective(s) & Hypothesis(es) (Optional) ......................................... 14 
3. 
METHODOLOGY ................................................................................................ 15 
3.1 
Study Design – General Aspects ............................................................................ 15 
3.1.1 
Data Source(s) ........................................................................................................ 16 
3.2 
Study Population .................................................................................................... 16 
3.3 
Inclusion Criteria ................................................................................................... 16 
3.4 
Exclusion Criteria .................................................................................................. 17 
3.5 
Participant Follow-up (Optional) ........................................................................... 17 
4. 
VARIABLES AND EPIDEMIOLOGICAL MEASUREMENTS ........................ 18 
4.1 
Exposures ............................................................................................................... 18 
4.1.1 
Definition of Primary Drug Exposure (Optional) .................................................. 18 
4.1.2 
Definition of Comparison Drug Exposure (Optional) ........................................... 18 
4.2 
Outcomes ............................................................................................................... 18 
4.3 
Other Variables and Covariates ............................................................................. 19 
5. 
STATISTICAL ANALYSIS PLAN ...................................................................... 19 

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5.1 
Statistical Methods – General Aspects................................................................... 19 
5.1.1 
Primary Objective(s):  Calculation of Epidemiological Measure(s) of 
Interest (e.g. descriptive statistics, hazard ratios, incidence rates, test/retest 
reliability) ............................................................................................................... 19 
5.1.2 
Secondary Objective(s):  Calculation of Epidemiological Measure(s) of 
Interest (e.g. hazard ratios, incidence rates, test/retest reliability) ......................... 19 
5.1.3 
Exploratory Objective(s):  Calculation of Epidemiological Measure(s) of 
Interest (e.g. hazard ratios, incidence rates, test/retest reliability) ......................... 20 
5.2 
Bias ........................................................................................................................ 20 
5.2.1 
Methods to Minimize Bias ..................................................................................... 20 
5.2.2 
Adjustment for Multiple Comparisons .................................................................. 20 
5.2.3 
Strengths and Limitations ...................................................................................... 20 
5.3 
Interim Analyses (Optional)................................................................................... 20 
5.4 
Sample Size and Power Calculations ..................................................................... 20 
6. 
STUDY CONDUCT AND REGULATORY DETAILS....................................... 21 
6.1 
Study Conduct ........................................................................................................ 21 
6.1.1 
Study Flow Chart and Plan .................................................................................... 21 
6.1.2 
Procedures .............................................................................................................. 21 
6.1.3 
Quality Control ...................................................................................................... 24 
6.2 
Protection of Human Subjects................................................................................ 24 
6.2.1 
Subject Informed Consent (Primary Data Collection Only) .................................. 25 
6.2.2 
Confidentiality of Study/Subject Data (Primary Data Collection Only) ............... 25 
6.3 
Collection and Reporting of Adverse Events/Adverse Drug Reactions ................ 25 
6.3.1 
Definition of Adverse Events (AE) ........................................................................ 25 
6.3.2 
Definition of Serious Adverse Events (SAE) ........................................................ 26 
6.3.3 
Definition of Adverse Drug Reactions (ADR) ...... Error! Bookmark not defined. 
6.3.4 
Collection of Adverse Events ................................ Error! Bookmark not defined. 
Causality collection ................................................................ Error! Bookmark not defined. 
Time period for collection of adverse events ......................... Error! Bookmark not defined. 
6.3.5 
Reporting of Adverse Events ................................................................................. 27 
7. 
LIST OF REFERENCES ....................................................................................... 29 
8. 
APPENDICES ....................................................................................................... 30 
9. 
ATTACHMENTS .................................................................................................. 45 
10. 
SIGNATURES ....................................................................................................... 46 
 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation or 
special term 
Explanation 
HRR 
Homologous Recombination Repair  
mCRPC 
Metastatic Castrate Resistant Prostate Cancer 
NCCN 
National Comprehensive Cancer Network 
PARP 
Poly-ADP Ribose Polymerase 
UCSD 
University of California San Diego 
 
 

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5 
RESPONSIBLE PARTIES 
Name 
Professional Title 
Role in Study Affiliation 
Email Address 
Rana McKay, MD 
Associate Professor 
Principal 
Investigator 
UC San 
Diego 
rmckay@health.ucsd.edu 
Matthew Savage, 
PhD 
Associate Professor 
Co-
investigator 
San Diego 
State 
University 
matthew.savage@sdsu.ed
u 
Audrey Dinh 
Staff Research 
Associate 
Regulatory 
Contact  
UC San 
Diego 
ahdinh@health.ucsd.edu 
Andrew Roberts 
Clinical Trials Project 
Manager 
Project 
Manager  
UC San 
Diego 
aroberts@health.ucsd.edu 
TBD 
Staff Research 
Associate  
Study 
Coordinator  
UC San 
Diego 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PROTOCOL SYNOPSIS 
This is a pilot study to improve germline genetic testing for patients with aggressive prostate 
cancer as recommended by the updated guidelines by the National Cancer Comprehensive 
Network (NCCN) in 2018. Implementation of germline testing in men with prostate cancer 
has been low, in part due to the lack of resources to educate patients on germline testing 
including a growing national shortage of genetics counselors. Given limited genetic 
counseling services and a growing number of patients who qualify for germline testing, there 
has been interest in developing models to educate patients on germline testing in the clinic. In 
this study, consented patients will undergo a low-risk intervention of an educational session 
with a trained staff member on germline testing in prostate cancer and if agreeable, 
subsequent germline cancer genetic testing via a commercial lab test. 
 
Background/Rationale: Germline testing is recommended for patients with high risk 
localized, locally advanced, and metastatic prostate cancer. Despite this recommendation, 
implementation of germline testing in prostate cancer has been suboptimal. This is due in part 
to a large number of patients who are eligible for testing and a national shortage of genetic 
counsellors. Given this, there is a need for novel strategies to engage oncology clinicians in 
germline testing and integrate germline testing into the clinic. Improving the rates of germline 
testing is vitally needed as pathogenic germline alterations can have therapeutic significance 
for a patient’s prostate cancer and can have implications for family members in terms of their 
own cancer risk.  
Objectives and Hypotheses: The primary objectives of this study are to both assess the 
feasibility of a patient educational program to improve germline genetic testing for eligible 
patients with prostate cancer and to assess the effectiveness of a patient educational program 
with regards to increasing germline genetic testing rate among adult prostate cancer patients 
who are recommended to receive germline testing per guidelines.  
We hypothesize that the intervention will be feasible with successful recruitment of our target 
sample size. We additionally hypothesize that the rates of germline testing among patients 
recruited to the study will be higher than rates of testing among patients not enrolled in the 
study. 
Methods: 
Study design: This is a prospective single arm quality improvement initiative for the use 
of a standardized educational intervention on germline testing in prostate cancer to 
improve the rates of germline genetic testing among patients recommended for testing. 
Patients who consent to the study will undergo a one-on-one in-person education session 
regarding the rationale and the benefits/risks of germline testing. Following the 
educational session, if a patient wishes to proceed with testing, they will sign the standard 
consent to proceed with germline testing via a commercial assay.  

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Data Source(s): Patients with prostate cancer treated in the UCSD Genitourinary 
oncology clinics.  
Study Population: Men with prostate cancer who meet the criteria for germline testing. 
Exposure(s): Consented patients will undergo an in-clinic educational session on 
germline testing in prostate cancer with a trained educator.  
Outcome(s): Assess the proportion of patients enrolled in the study who underwent 
germline testing to the proportion of patients who did not enroll in the study. Assess the 
effect of a patient educational program on increasing germline genetic testing rate among 
adult prostate cancer patients who are recommended to receive germline testing per 
NCCN guidelines.  .  
Sample Size Estimations: Target accrual is 50 patients in 12 months.  
Statistical Analysis: For the primary endpoints of feasibility of implementing an 
educational intervention, this will be assessed by the accrual rate over 12 months. For the 
endpoint of efficacy of the intervention in improving rates of germline testing, the 
proportion of patients who undergo germline testing in this study will be compared to the 
proportion of patients who undergo germline testing who were eligible, but not enrolled 
into this study during the study time period.  
 

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AMENDMENT HISTORY 
Date 
Section of study protocol 
Amendment or update 
Reason 
 
 
N/A 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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MILESTONES 
Milestone 
Planned date 
Finalize survey instruments 
July 2021 
Finalize Redcap database along with CRFs 
August 2021 
Hiring of clinical research coordinator 
August 2021 
Completion of video  
September 2021 
Training of research coordinator 
August- September 2021 
Start of accrual 
October 2021 
6-month assessment of accrual 
April 2022 
Database lock 
October 2022 (or sooner if 50 patients are 
accrued) 
Analysis 
November 2022  
ASCO Abstract 
January 2023 
First Manuscript  
March 2023 
 
 

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1. 
BACKGROUND AND RATIONALE 
 
1.1 
Background  
 
Prostate cancer is the most common cancer in men in the United States with a lifetime risk of 16% and 
the second leading cause of cancer-related death in men in the United States. While patients with 
localized prostate adenocarcinoma have 5-year survivals that approach 100% per the Surveillance, 
Epidemiology, and End Results (SEER) Program database, outcomes are much more dismal in the 
metastatic setting with an estimated 5-year survival of 30% (1). Given this, there has been considerable 
effort to further understand the pathogenesis and genetic underpinnings of locally advanced and 
metastatic prostate cancer.  
 
While the average age of diagnosis of prostate cancer is 66 years old (1), there is increasing evidence 
for inherited genetic susceptibility to prostate cancer, particularly in patients with advanced prostate 
cancer. The most common germline mutations seen are those in the DNA repair pathway, and more 
specifically, the homologous recombination repair pathway, including BRCA1/2 which can predispose 
to not only prostate cancer, but breast, ovarian, pancreatic, and skin cancers. In addition to the known 
incidence of mutations in BRCA1 and BRCA2, germline mutations have been noted in other DNA 
repair genes including ATM, CHEK2, PALB, and others. Prostate cancer has been also been previously 
reported in patients with Lynch syndrome, another inherited genetic syndrome due to mutations in 
either MLH1, MSH2, EPCAM, MSH6, and PMS2. 
 
A large multi-institutional study evaluated the prevalence of germline DNA repair gene mutations in 
692 men with metastatic prostate cancer unselected for age and family history from eight centers, 
results of which are shown in Table 1 (2). Germline DNA was isolated and used for multiplex 
sequencing assays to assess 20 DNA repair genes. The study demonstrated that 84 germline DNA 
repair gene mutations were identified in 11.8% of men in 16 genes. In men with Gleason 8-10 prostate 
cancer, the prevalence of germline DNA repair gene mutations is 6%. Mutations were found most 
frequently in the following genes: BRCA2 (37 men, 5.3%), ATM (11 men 1.6%), CHEK2 (10 men 
1.9%) and BRCA1 (6 men 0.9%).   
 
Table 1. Pathogenic Germline DNA Repair Aberrations in Prostate Cancer.  
 
Germline Mutations in DNA Repair Genes 
Metastatic Prostate Cancer  
n=84/692 
11.8% 
Localized Prostate Cancer  
n=23/499 
4.6% 
Gleason 6  
n=2/45 
4% 
Gleason 7 
n=9/249 
4% 
Gleason 8-10 
n=12/205 
6% 
NCCN Low-Intermediate 
Risk 
n=4/162 
2% 
NCCN High-risk  
n=19/337 
6% 
No Cancer Diagnosis  
n=1433/53,105 
2.7% 
NCCN=National Comprehensive Cancer Network. 

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Given this data, the most recent iteration of the NCCN guidelines for prostate cancer, published in 
April 2019, notes “Germline genetic testing is recommended for all men with high-risk, very-high-risk, 
regional, or metastatic prostate cancer.” Additionally, it is recommended that patients with localized 
low or intermediate risk prostate cancer with a positive family history or presence of intraductal 
histology are recommended to undergo germline testing (3). In addition to the NCCN 
recommendations, there have been other published recommendations. At the Philadelphia Prostate 
Cancer Conference, an expert panel convened to develop guidelines for germline testing which is 
shown in Table 2 (4). With regards to germline testing in localized prostate cancer, a collaboration 
between AUA, ASTRO, and SUO recommended consideration of genetic counseling for patients with 
high-risk localized prostate cancer and a strong family history of breast, ovarian, pancreatic, or other 
GI tumors (5). It is important to note that there are discrepancies among these guidelines and the 
NCCN guidelines are primarily utilized by payers, including Medicare, to determine coverage for 
testing. 
 
Table 2: Guidelines on Germline Testing in Prostate Cancer 
Organization 
Source 
Guidelines 
National 
Comprehensive 
Cancer Network 
Prostate Cancer, 
Version 4.2019 
All men with high-risk localized, very-high-risk 
localized, locally advanced, or metastatic prostate cancer.  
• 
Family history criteria and consideration to 
prompt genetic testing: 
A strong family history of prostate cancer 
consists of: brother or father OR  
• 
Multiple family members who were diagnosed 
with prostate cancer (but not clinically localized 
Grade Group 1) at less than 60 years of age or 
who died from prostate cancer  
• 
Ashkenazi Jewish ancestry 
• 
≥3 cancers on same side of family, especially 
diagnoses ≤50 years of age: bile duct, breast, 
colorectal, endometrial, gastric, kidney, 
melanoma, ovarian, pancreatic, prostate (but not 
clinically localized Grade Group 1), small bowel, 
or urothelial cancer  
• 
Genetic testing in the absence of family history 
or clinical features (eg, high- or very-high-risk 
prostate cancer, intraductal histology) may be of 
low yield. The patient should be counseled to 
inform clinicians of any update to family history. 

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Expert Panel 
Philadelphia 
Consensus Meeting 
Publication, 2017 
Men meeting any one of the following suggested criteria 
should undergo genetic counseling and genetic testing: 
• 
All men with prostate cancer from families meeting 
established testing or syndromic criteria for the 
following: 
○ Hereditary breast and ovarian cancer syndrome 
(HBOC) (Consensus: 93%) 
○ Hereditary prostate cancer (HPC) (Consensus: 
95%) 
○ Lynch syndrome (LS) (Consensus: 88%) 
• 
Men with prostate cancer with two or more close 
blood relatives on the same side of the family with a 
cancer in the following syndromes: 
• 
Post-consensus discussion included 
consideration of age cutoff for this criterion. A 
specific age cutoff will require additional data, 
and age at diagnosis is important to inquire in the 
genetic counseling session with patients. 
o 
HBOC (Consensus: 93%) 
o 
HPC (Consensus: 86%) 
o 
LS (Consensus: 86%) 
• 
All men with metastatic castrate-resistant prostate 
cancer should consider genetic testing (Consensus: 
67%). Post-consensus discussion also included 
consideration of testing men with metastatic, 
hormone-sensitive prostate cancer to identify 
germline mutations to inform potential future 
treatment options and cascade testing in families. 
• 
Men with tumor sequencing showing mutations in 
cancer-risk genes should be recommended for 
germline testing, particularly after factoring in 
additional personal and family history (Consensus: 
77%). 
American 
Urological 
Society 
Clinically Localized 
Prostate Cancer: 
AUA/ASTRO/SUO 
Guideline, 2017 
• The Panel recommends that clinicians take detailed 
family history of cancers and give consideration to 
patient referral for genetic screening and counseling 
for men with localized high-risk prostate cancer, 
particularly in the setting of family history of first-
degree relatives with cancers of breast, ovary, 
pancreas, other gastrointestinal cancers, and 
lymphoma. 
 
Given that prostate cancer is the most common cancer among men, the recommendation to test such a 
large population of patients has placed significant demands on health systems and clinical workflows. 
There is increased demand for trained genetics professionals to provide quality counseling and testing 
services. Genetic counselors are trained in assessing family history for genetic risk, ordering 

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appropriate genetic testing and interpreting the results, discussing appropriate cancer screening 
recommendations, and helping families adapt to genetic testing results. Unfortunately, access to these 
services is often limited, with the majority of the small workforce of genetic counselors and clinical 
geneticists often centered in urban and academic areas (6). In 2016, The Genetic Counselor Workforce 
Working Group estimated a 72% growth in the workforce between 2017-2026, with the demand for 
genetic counselors not expected to meet population equilibrium until 2024-2030 (7). This limited 
access may necessitate other healthcare clinicians, such as oncologists, primary care physicians, or 
urologists, taking on some of the responsibilities of genetic testing. With expanded clinician education 
which utilizes the expertise and guidance of genetic counselors, healthcare clinicians can deliver 
quality genetic counseling education with the support from the geneticists for questions or more 
complicated cases. Taken together, this highlights a critical need for expanding genetic services and 
developing novel approaches to care outside of the historic delivery model (10). 
 
While germline testing in prostate cancer offers patients further information regarding their genetic 
risk of malignancy, it also has therapeutic implications. As discussed previously the most commonly 
detected germline mutations include BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51, which 
compromise the DNA repair or homologous repair pathway. This pathway is involved in the repair of 
double stranded DNA breaks and maintenance of genomic stability (2). In cells with deficiency in 
homologous recombination repair, inhibition of PARP results in cell death via synthetic lethality. In a 
phase 2 trial of olaparib, a PARP inhibitor, in patients with metastatic CRPC with homologous repair 
mutations, 88% (n=14/16) of patients demonstrated a response to olaparib (6). Based on these data, the 
FDA granted “breakthrough therapy” designation status to the PARP inhibitor olaparib in metastatic 
CRPC in 2016. PROfound, a phase III trial examining olaparib compared to standard of care 
enzalutamide or abiraterone in mCRPC patients with homologous recombination repair alterations. In 
the PROfound trial, the radiographic progression-free survival with olaparib was 7.39 months 
compared to 3.55 months in patients treated with either abiraterone or enzalutamide (HR 0.34, 95% CI 
0.25, 0.47, p<0.0001). Based on the results of this study, the FDA recently granted approval for 
olaparib in the treatment of mCRPC that has progressed on abiraterone or enzalutamide harboring a 
somatic or germline alteration in an HRR gene. 
 
1.2 
Rationale 
 
Given the prevalence of germline mutations in 10-12% of patients with advanced prostate cancer and 
the diagnostic and therapeutic implications of germline testing, improving the frequency of testing is 
greatly needed. Here, we propose a pilot study to improve germline testing among patients with 
prostate cancer via implementation of an in-clinic educational intervention on germline testing with a 
trained staff member. We will start by assessing baseline knowledge and attitudes on germline testing 
in prostate cancer among oncologists and urologists. An educational session will be provided for all 
oncologists and urologists to review germline testing guidelines. We will then screen clinics for 
patients with prostate cancer who meet criteria for germline testing per NCCN guidelines and offer 
them the opportunity to meet with the trained educator to review germline testing. Following this 
standardized educational session, patient’s will be given the opportunity to consent for a commercially 
available germline genetic testing platform.  

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2. 
OBJECTIVES AND HYPOTHESES 
 
2.1 
Primary Objective(s) & Hypotheses 
Objectives 
(1) To assess the feasibility of a patient educational program to improve germline genetic testing 
for eligible patients with prostate cancer. 
(2) To assess the effectiveness of a patient educational program with regards to increasing 
germline genetic testing rate among adult prostate cancer patients who are recommended to 
receive germline testing per NCCN guidelines.   
 
Hypotheses 
(1) We hypothesize intervention will be feasible with successful recruitment of our target sample 
size.  
(2) We hypothesize that the rates of germline testing among patients recruited to the study will be 
higher than rates of testing among patients not enrolled in the study. 
2.2 
Secondary Objective(s) & Hypotheses 
Objectives 
(1) To assess patients’ baseline knowledge of germline testing and the change in knowledge of 
germline testing with the educational intervention.  
(2) To assess a patient’s baseline attitudes towards germline testing and assess the impact of an 
education interventional on patient perceptions of germline testing.  
(3) To assess the impact of germline testing results on prostate cancer management.  
(4) To assess prevalence of pathogenic germline mutations in patient population. 
 
Hypotheses 
(1) We hypothesize that the educational intervention will lead to an improvement in knowledge of 
germline testing. 
(2) We hypothesize that the educational intervention will lead to a more favorable attitude towards 
germline testing among patients enrolled in the study.  
(3) We hypothesize that the educational intervention will result in greater prescribing of targeted 
therapies given detection of germline alterations in the HRR pathway.  
(4) We hypothesize that the educational session will improve patient’s perception and familiarity 
with germline testing.  
  
2.3 
Exploratory Objective(s) & Hypotheses  
Objectives 
(1) To describe the demographic and clinical characteristics among all patients who received 
germline testing and subsequently, stratify by presence of germline mutations in cancer 
susceptibility genes.  
 
Hypotheses 
(1) We hypothesize that patients with pathogenic germline alteration have more aggressive disease 
patterns in both the localized and advanced settings.  

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3. 
METHODOLOGY 
3.1 
Study Design – General Aspects 
 
We will then screen genitourinary oncology clinics at UC San Diego Health System to identify 
patients who are eligible for germline testing. After approval from their treating physician, we will 
approach patients in the clinic and introduce the educational intervention, which will consist of a 
one-on-one in-person educational sessions reviewing the rationale and the risks and benefits of 
germline testing. A virtual educational session was added due to the COVID-19 pandemic and will 
ideally occur over the Epic video chat platform, Doximity video chat, but can also occur via 
telephone for patients who are unable to use video chat. 
 
The educational intervention will occur with a clinical research coordinator who will be trained to 
educate on germline testing in prostate cancer. At the start of the session, the patient will be given 
a short questionnaire (Appendix A) to assess their understanding about germline and genetic 
testing, along with a Family History questionnaire (Appendix B). Following this, the session will 
then include a one-on-one review of an educational handout on germline testing in prostate cancer 
(Appendix E). The handout will provide a concise, yet comprehensive review of germline testing 
including:  
 
1. Overview of genetic germline testing 
2. Rationale for germline testing in prostate cancer 
3. Implications of germline testing in terms of patient’s clinical care 
4. Implications to family 
5. Overview of results including discussion of pathogenic germline mutation and variants 
of unknown significance  
6. Discussion of benefits and risks of testing  
 
Session Overview 
Time (approximately) 
Objective 
1-5 minutes  
Introduction 
10 minutes 
Pre-intervention survey 
5 minutes 
Video 
10 minutes 
Review of brochure 
5 minutes 
Time for patient to ask questions 
10 minutes 
Post-intervention survey 
 
The patient will then have an opportunity to ask questions. If a patient wishes to proceed with 
testing, they will sign the standard consent to proceed with germline testing and the patient’s 
clinician will be notified of intent to proceed with germline testing. Patients can elect to decline 
testing, defer testing to a later time, or request referral to genetic counseling to discuss the testing. 
We will track patterns of patient decision making following the educational intervention. Upon a 
patient deciding to pursue testing, testing will consist of a prostate cancer germline panel with a 
commercially available blood or saliva-based assay. Following the educational intervention, the 
patient will be asked to complete a short patient education and satisfaction questionnaire 
(Appendix D). Upon receipt of the results, the coordinator will alert the patient’s clinician, who 
will then share the results with the patient either in clinic or by phone. If the results show a 

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pathogenic germline mutation, the patient will be referred to see the UCSD cancer medical 
genetics clinic for consultation with a genetics counselor. Additionally, the patient can elect to see 
a genetics counselor independent of the test results once the test results are reviewed. If a patient 
pursues genetic testing, following receipt of results, the patient’s clinicians will be asked to 
complete a short survey on to assess how the results of germline testing affected the patient’s 
current and future management (appendix D). There will be capacity for patients to complete 
questionnaires electronically. Additionally, to systematically understand the scope of questions 
asked by patients which will provide opportunity to optimize the educational intervension, we will 
record the educational sessions.  
 
3.1.1 
Data Source(s) 
This is a single center study of prostate cancer patients treated in the UC San Diego genitourinary 
oncology clinics. Data will be captured in secure RedCap database. Data to be captured including 
demographics, clinical characteristics, disease characteristics and results of study questionnaires.  
3.2 
Study Population 
 
The target population for this study is patients older than 18, with prostate cancer who meet the NCCN 
criteria for germline testing and who have not undergone prior germline testing.  
Subjects will include those patients seen at a facility in the UCSD Health System. Genitourinary 
oncology clinics will be screened 1 week in advanced for eligible patients. Recruitment procedures 
will also involve the review of subject records by designated study personnel (e.g., investigators and/or 
study coordinators) in order to identify potentially eligible subjects.  Since Protected Health 
Information (PHI) will be accessed via the hospital’s medical record database and scheduling system 
(e.g., EPIC/IDX) prior to contacting the potential subject about the research study, we have been 
granted a partial waiver of HIPAA authorization for access to PHI for purposes of prescreening only.   
For patients who are eligible for the trial, the investigator will approach the subject and offer 
participation in the trial. Standard HIPAA authorization to collect research data from the subject's 
medical record will be obtained at the time of informed consent. Given the COVID-19 pandemic, we 
are conducting sessions both in clinic and virtually. This will primarily occur via video chat or 
telephone. Given that this is a low-risk intervention of an educational session, we believe that virtual 
consenting is also appropriate here given the current pandemic.  
For patients who decline the intervention or have not been approached at the time of analysis, these 
patients will be considered a separate cohort for comparison to the intervention cohort.  
3.3 
Inclusion Criteria 
1. Men, age greater than or equal to 18 years of age. 
2. Diagnosis of prostate cancer of any histology. 
3. Must meet NCCN guidelines for germline testing (see table below for specific definition of 
risk groups). 
a. Men with very low, low or intermediate risk prostate per NCCN guidelines with a positive 
family history or intraductal histology OR 

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- 
Family history here is considered significant if the patient has a first degree 
relative with prostate cancer or more than one first/second degree relative with 
prostate cancer.  
- 
≥3 cancers on same side of family, especially diagnoses ≤50 years of age: bile 
duct, breast, colorectal, endometrial, gastric, kidney, melanoma, ovarian, 
pancreatic, prostate (but not clinically localized Grade Group 1), small bowel, or 
urothelial cancer  
b. Men with high-risk, very-high risk (see Table 3 for NCCN definitions of risk groups), 
lymph node positive, or metastatic prostate cancer independent of family history of 
histology.  
 
NCCN definitions of risk groups in localized prostate cancer 
 
3.4 
Exclusion Criteria 
Patients are excluded from the study if they: 
1. Have had prior germline testing. 
2. Have somatic genetic testing that is positive for a possible germline variant.   
3.5 
Participant Follow-up  
 
Patients will be followed for 24 months following the educational session. We will capture deferred 
decisions to pursue germline testing during the 24-month follow up period. Data on oncologic 
outcomes, prostate cancer management, and cancer surveillance will be obtained from the medical 
record.  

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4. 
VARIABLES AND EPIDEMIOLOGICAL MEASUREMENTS 
 
4.1 
Exposures  
4.1.1 
Definition of Primary Exposure  
The primary exposure to be tested is an educational session including video on germline testing and 
review of brochure on germline testing in men with prostate cancer. See attachment.  
4.1.2 
Definition of Comparison Exposure  
The comparison group will include individuals with prostate cancer who meet criteria for 
germline testing however were not approached about participating in the intervention or were 
approached and declined participating in the educational intervention. In this context, 
germline testing education will be at the discretion of the treating medical team.  
4.2 
Outcomes 
 
 
Primary Endpoints 
1. The proportion of patients who undergo germline testing among those who are 
enrolled to the study compared to the proportion of patients who undergo germline 
testing who were eligible, but not enrolled into this study during the study time period 
2. Feasibility of implementing an educational intervention for men with prostate cancer 
at risk of having a hereditary cancer syndrome. This will be assessed by: 
• 
Accrual rate by month. 
• 
Proportion of patients who consent to educational intervention among 
those who are approached (stratified by whether consent was 
performed in-person or virtually). 
Secondary Endpoints 
1. Patient understanding of germline testing before and after the education intervention 
based on questionnaire responses. 
2. Patient-reported opinions on germline testing before and after intervention, and 
patient-reported satisfaction after educational intervention based on questionnaire 
responses. 
3. Physician responses regarding how the germline testing result changed patient 
management.  
4. Prevalence of pathogenic germline mutations among study patients who undergo 
germline testing. 
 
Exploratory Endpoints 
1.  Clinical factors (patient and family history, disease characteristics, and outcomes) that 
are associated with the presence of a germline mutation in a cancer susceptibility gene. 
 

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4.3 
Other Variables and Covariates 
We will capture the following additional demographic, clinical, and disease variables: 
• 
Demographic data: Age, Marital Status, Race, Ethnicity, Employment Status, Clinician, 
Primary Language, Country of Birth, Education Level. 
• 
Previous medical history: Comorbidities, Smoking History, and Family History of 
Malignancies. 
• 
Disease characteristics: Date of Diagnosis, Site of Disease, Site(s) of Metastasis, if applicable, 
Histology/Grade/Pathologic Parameters, PSA, Stage, Somatic Molecular Profile, Date of 
Collection of Tissue Analyzed, Type of Tissue Analyzed. 
• 
Treatment data: Date of Surgery, Date of Radiation, Dose of Radiation, Systemic Therapy. 
• 
Treatment outcomes data: Toxicity, Dose Reduction, Reason for Dose Reduction, Response, 
Progression, Survival.  
4.4 
Statistical Analysis Plan 
4.5 
Statistical Methods – General Aspects 
4.5.1 
Primary Objective(s):  Calculation of Epidemiological Measure(s) of Interest 
(e.g. descriptive statistics, hazard ratios, incidence rates, test/retest reliability) 
Primary Endpoints 
With regards to the primary endpoint, at the completion of the study, the proportion of patients 
who complete germline testing among all who are enrolled to the study will be computed. A 
sample size of 50 patients produces a two-sided 95% confidence interval on the proportion with a 
width ranging from 0.27 to 0.29 when the observed proportion ranging from 0.3 to 0.7. For 
proportions, 95% confidence intervals will be calculated using the exact method. 
 
We will also compute the proportion of patients who completed germline testing for all eligible 
prostate cancer patients evaluated in clinic but not enrolled into this study during the study period. 
Characteristics between these two groups will be compared using Fisher’s Exacts or Wilcoxon 
Rank Sum tests. The proportion of patients who underwent germline testing in the intervention vs 
non-intervention cohorts will be compared using Fisher’s exact test.  
4.5.2 
Secondary Objective(s):  Calculation of Epidemiological Measure(s) of Interest 
(e.g. hazard ratios, incidence rates, test/retest reliability) 
 
Secondary endpoints including germline mutation frequency, patient understanding of germline 
testing, and medical management from germline testing will be described using descriptive 
statistics such as bar graphs, box plots, percentages, means and standard deviations, etc.  
 

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4.5.3 
Exploratory Objective(s):  Calculation of Epidemiological Measure(s) of 
Interest (e.g. hazard ratios, incidence rates, test/retest reliability) 
- 
Associations between clinical factors and pathogenic germline alterations will be 
evaluated using Odds Ratio.  
- 
Impact of germline testing on prostate cancer and cancer surveillance management will be 
qualitatively described.  
4.6 
Bias 
4.6.1 
Methods to Minimize Bias 
We aim to reduce bias through several methods including systemically screening medical oncology 
and urology clinics to identify eligible patients. The research coordinator will have a rotating schedule 
of clinics to screen to ensure systematic non-bias selection of eligible patients. Additionally, the 
intervention will be offered in multiple media modalities including in-person, video, and telephone to 
accommodate patient preferences. The intervention and video will be available in English and Spanish 
to further limit selection bias. Furthermore, there is capacity to perform the intervention in the clinic 
coinciding with the patients clinic appointment or at a separate time that is feasible for the patient. 
4.6.2 
Adjustment for Multiple Comparisons 
Not applicable.  
4.6.3 
Strengths and Limitations 
The primary strength of the study is the novel approach to integration of germline testing education 
into the clinic. The study will assess the feasibility of an in clinic educational model led by a clinical 
research coordinator. This will also assess the feasibility of how other clinicians outside of genetics 
can provide some degree of genetic counselling that could be applicable to medical assistants, nurses, 
and advanced practice providers.  
 
A key limitation of this study include bias with regards to recruitment, which we hope to mitigate by 
offering the study to all eligible patients in all GU oncology clinics, offering the session in English and 
Spanish, and offering a virtual option.  
4.7 
Interim Analyses (Optional) 
N/A 
4.8 
Sample Size and Power Calculations 
 
With regards to the primary endpoint, at the completion of the study, the proportion of patients 
who complete germline testing among all who are enrolled to the study will be computed. A 
sample size of 50 patients produces a two-sided 95% confidence interval on the proportion with a 
width ranging from 0.27 to 0.29 when the observed proportion ranging from 0.3 to 0.7. 

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5. 
STUDY CONDUCT AND REGULATORY DETAILS 
5.1 
Study Conduct 
5.1.1 
Study Flow Chart and Plan 
 
Scheduled of Assessments 
 
Pre- Study 
Intervention 
Follow Up 
Family History Questionnaire 
 
X 
 
Pre-Intervention Patient Questionnaire  
 
X 
 
Educational Session  
 
X 
 
Post Intervention Patient Questionnaire 
 
X 
 
Germline Results Review  
 
 
X 
Clinician Questionnaire 
 
 
X 
 
5.1.2 
Procedures 
Recruitment: 
Pre-screening procedures will involve the review of subject records by designated study personnel in 
order to identify potentially eligible subjects. Protected health information (PHI): Patient Name, 
Medical Record Number, Date of Birth, date and time of upcoming appointments, medications, and 
disease status, will be accessed via the hospital’s medical record database and scheduling system prior 
to contacting the potential subject about the research study. The Slicer Dicer Epic functionality may 
also be utilized to identify eligible patients in addition to systematic review of clinician schedules. A 
partial waiver of HIPAA authorization for access to PHI for purposes of pre-screening is being 
requested. This study meets the following requirements for this request per 45 CFR 164. 512(i)(2)(ii):  
1. The use or disclosure of PHI involves no more than minimal risk to the privacy of 
individuals as the only risk is loss of confidentiality and all reasonable measures to protect 
confidentiality will be carried out.  

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2. Granting of the waiver will not adversely affect privacy rights and welfare of the 
individuals whose records will be used as the only risk is loss of confidentiality and all 
reasonable measures to protect confidentiality will be carried out.  
3. The pre-screening could not practicably be conducted without a waiver because we need to 
search project the EPIC electronic database to identify eligible subjects. 
4. The project could not practicably be conducted without use of PHI because demographic 
and clinic information are needed in order to identify eligible subjects.  
5. The privacy risks are low relative to the anticipated benefits of research. The privacy risks 
are minimal since all reasonable efforts to protect confidentiality will be performed and 
there is the potential to gain scientific knowledge that will benefit future genitourinary 
cancer patients.  
6. An adequate plan to protect identifiers from improper use and disclosure is included in this 
research proposal.  
7. An adequate plan to destroy the identifiers at the earliest opportunity is included in the 
research proposal.  
8. The PHI will not be re-used or disclosed for other purposes. 
 
A partial waiver of informed consent is being requested for pre-screening. The reasons underlying this 
request include the following per 45 CFR 46.116:  
1. The (pre-screening) research involves no more than minimal risk to the subjects as the 
only risk is loss of confidentiality and all reasonable measures to protect confidentiality 
will be carried out;  
2. The waiver will not adversely affect the rights and welfare of the subjects used as the only 
risk is loss of confidentiality and all reasonable measures to protect confidentiality will be 
carried out;  
3. The (pre-screening) research could not practicably be carried out without the as the 
research staff needs to search the EPIC electronic database to identify eligible subjects; 
and  
4. Whenever appropriate, the subjects will be provided with additional pertinent information 
after participation. 
 
Informed Consent: 
Individuals who fulfill the eligibility criteria will be offered participation in this study. The patient’s 
treating physician will authorize the investigator or study coordinator to meet with the patient. Consent 
may occur in-person, via video chat, or via telephone. Study candidates will be asked to provide 
written consent, using an IRB-approved informed consent form. The investigator or study coordinator 
will describe the study to potential participants. The investigator or study coordinator will provide 
potential participants with a blank informed consent form. The individual will be given ample time to 
read this consent form at the same visit or may take it with them to read at another time. The study 
candidate will be given the opportunity to ask and receive answers to all questions they may have 
about the study, its risks and benefits, and the consent form itself before signing the consent form. As 
this research is subject to HIPAA Privacy Rule provisions, study candidates will also be requested to 
sign a separate HIPAA authorization form specific to the research study for the use of PHI. The 
consent process will be appropriately documented. 
 
Survey Administration: 
All surveys will be available as secure links sent to the participant’s provided email through REDCap. 
The patients can also opt to complete the surveys by phone with the research assistant or on paper.  

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Family History Questionnaire: The Family History Questionnaire (FHQ) is the standard method of 
self-reported data collection for patients at in the Genitourinary Program at UCSD. This has been 
modeled from Family History Questionnaires utilized within our Cancer Genetics Program at UCSD 
and others across the country but modeled for men with prostate cancer. 
 
Pre-Intervention Patient Questionnaire: The pre-intervention patient questionnaire is a brief 16-item 
investigator-developed knowledge and attitude scale applicable to this population. It was developed 
through an expert panel to determine if participants are able to recall key core components about multi-
gene panel testing and capture attitudes about genetic testing. This survey is estimated to take 10 
minutes to complete. 
 
Post-Intervention Patient Questionnaire: The post-intervention patient questionnaire is a brief 24-item 
investigator-developed knowledge and attitude scale applicable to this population. It includes the same 
14 knowledge and attitude items from the pre-intervention survey to assess impact of the educational 
intervention. It was developed through an expert panel to determine if participants are able to recall 
key core components about multi-gene panel testing and capture attitudes about genetic testing. There 
is also a 10-item scale to capture satisfaction with educational intervention. This survey is estimated to 
take 10 minutes to complete. 
 
Post-Results Clinician Questionnaire: The post-result clinician questionnaire is a brief 6-item 
investigator-developed scale to assess whether the genetic testing results altered clinical practice for 
any given patient including change in disease monitoring, change in recommended treatment, referral 
to genetic counseling and other parameters. This survey is estimated to take 5 minutes to complete. 
 
Intervention Administration: 
The educational intervention including video and brochure review will be administered by a study 
team member in a consult or exam room on a password-protected tablet or on a computer when 
performed in person. For remote visits, a study team member will provide the participant with 
either an electronic or paper copy of the brochure for review and will share the educational video 
electronically via video functionality of EPIC or Doximity with the patient. For patients who 
prefer a telephone intervention, the video will still be made audible but not visible to the patient 
for review. The participant may choose to proceed or decline genetic testing after the educational 
intervention. If the participant has any questions regarding the study, the study team member may 
answer them. If the participant has any concerns or questions about genetic testing, the study team 
member will refer them to the educational materials provided, their clinician, or connect them to 
the Principal Investigator. 
 
Withdrawal of Participation: 
A participant is free to withdraw from the study at any time for any reason without prejudice to his 
future medical care by the physician or at the institution. If the participant decides that he does not 
want to continue to be a part of this study, he will contact PI Dr. Rana McKay or the study coordinator. 
Their previously data will be destroyed if requested by the participant. In some cases, it may be 
impossible to stop future if the resulting data have already been analyzed and/or shared. 
 
 

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5.1.3 
Quality Control 
Monitoring 
Before the first subject is recruited into the study, the local Marketing Company, MEOR Delivery 
Director, MEOR Operations Lead or CRO Representative will: 
• 
Establish the adequacy of the facilities and the investigator’s capability to appropriately 
select the sample 
• 
Discuss with the investigator(s) (and other personnel involved with the study) their 
responsibilities with regards to protocol compliance, and the responsibilities of AstraZeneca or 
its representatives. This will be documented in an Observational Study Primary Agreement 
between AstraZeneca/delegate and the investigator. 
During the study the local MC representative or delegate can implement different activities to assure 
compliance with AZ standards of quality. These activities could include but are not limited to: 
 
Contacts with the sites to: 
• 
Provide information and support to the investigator(s) 
• 
Confirm that the research team is complying with the protocol and that data are being 
accurately recorded in the case report forms (CRFs) 
• 
Ensure that the subject informed consent forms are signed and stored at the investigator’s site 
• 
Ensure that the CRFs are completed properly and with adequate quality. 
 
Monitoring activities for: 
• 
Checking of ICFs 
• 
Checking that subjects exist in medical records 
The extent and nature of monitoring will be decided during the study planning based on design, 
complexity, number of subjects, number of sites, etc.  Observational Research Center (multi country) 
/Marketing Company (MC) will give some recommendations that could be locally adapted. 
Different signals (eg, high rejection rate in a site) should be used as potential identification of low 
protocol compliance by investigators. 
If these or any other signal occurs or if the local coordinator is suspicious of a potential non-optimal 
level of protocol compliance by the site investigator, specific measures should be adopted to evaluate 
the situation, identify the issue and implement specific action plans to correct the situation. 
 
Training of Study Site Personnel 
The Principal Investigator will ensure that appropriate training relevant to the Observational Study is 
given to investigational staff, and that any new information relevant to the performance of this 
Observational Study is forwarded to the staff involved.  
5.2 
Protection of Human Subjects 
The Observational Study will be performed in accordance with ethical principles that are consistent 
with the Declaration of Helsinki, ICH GCPs, GPP and the applicable legislation on Non-Interventional 
Studies and/or Observational Studies.  
 
The Investigator will perform the Observational Study in accordance with the regulations and 
guidelines governing medical practice and ethics in the country of the Observational Study and in 
accordance with currently acceptable techniques and know-how. 
 

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The final protocol of the Observational Study, including the final version of the Subject Informed 
Consent Form, must be approved or given a favourable opinion in writing by the Ethics 
Committee/Institutional Review Board (IRB)/Independent Ethics Committee (IEC). 
The Ethics Committee/IRB/IEC must also approve any amendment to the protocol and all advertising 
used to recruit subjects for the study, according to local regulations.  
5.2.1 
Subject Informed Consent (Primary Data Collection Only) 
The Investigator will ensure that the subject is given full and adequate oral and written information 
about the nature, purpose, possible risk and benefit of the Observational Study.  Subjects must also be 
notified that they are free to discontinue from the Observational Study at any time.  The subjects 
should be given the opportunity to ask questions and allowed time to consider the information 
provided. 
The signed and dated subject informed consent must be obtained before any specific procedure for the 
Observational Study is performed, including: 
• 
Interview with the investigator 
• 
Fulfil the questionnaires  
• 
CRFs completion. 
The Investigator must store the original, signed Subject Informed Consent Form.  A copy of the signed 
Subject Informed Consent Form must be given to the subject. 
5.2.2 
Confidentiality of Study/Subject Data (Primary Data Collection Only) 
The Subject Informed Consent Form will incorporate wording that complies with relevant data 
protection and privacy legislation.  Pursuant to this wording, subjects will authorize the collection, use 
and disclosure of their personal data by the Investigator and by those persons who need that 
information for the purposes of the Observational Study. 
The Subject Informed Consent Form will explain that Observational Study data will be stored in a 
computer database, maintaining confidentiality in accordance with the local law for Data Protection. 
 
The Subject Informed Consent Form will also explain that for quality check purposes, a monitor of AZ 
or a monitor of company representing AZ, will require direct access to the signed subject informed 
consent forms.  In case source data verification will be planned as quality check, the Subject Informed 
Consent Form will explain that for data verification purposes, monitor of AZ or a monitor of company 
representing AZ may require direct access to source documents that are part of the hospital or practice 
records relevant to the Observational Study. 
5.3 
Collection and Reporting of Adverse Events/Adverse Drug 
Reactions 
5.3.1 
Management of Adverse Risk  
a. Psychologic side-effects 
 

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Potential side effects include psychological distress due to issues raised regarding the potential 
presence of a hereditary cancer syndrome. It is possible that participants may experience anxiety as a 
result of the questionnaire process. Experience from our previous questionnaire protocols as well as 
clinical testing programs at the UCSD suggests that individuals do adjust to both information and the 
experience of participation in a predisposition testing program. There is variation in the degree to 
which participants rely on project staff for assistance. The program staff will be available throughout 
the program to respond to clinical questions and concerns that arise. Participants will also be offered 
the opportunity to receive psychological support from the center psychologist or social worker. 
 
b. Privacy  
 
There have been reports about the possibility of identifying an individual from his or her genetic 
information along with factors such as age and place of residence, even after the name has been 
removed. We believe that the chance of this happening in this study is very small but not zero, and will 
take measures to minimize such occurrences. Confidentiality will be assured by the coding of the 
questionnaires with a unique study ID assigned to each participant and family member. Files will be 
kept in password protected computer databases accessible to only study staff. The listing of participant 
names and numbers will be kept in a separate locked file within the Clinical Trials Office. It will be 
recommended to participants that they inform their physician of their test results. 
 
c. Insurance Discrimination  
 
The study itself is testing and educational intervention and genetic testing will be performed as 
standard of care should a participant decide to pursue genetic testing. The Genetic Information 
Nondiscrimination Act of 2008 (GINA) protects Americans from being treated unfairly because of 
differences in their DNA that may affect their health, and may prevent discrimination by health 
insurers and employers based on genetic information. GINA is intended to ease concerns about 
discrimination that might keep some people from getting genetic tests that could benefit their health, 
and enable people to take part in research studies such as this without fear that their DNA information 
might be used against them by health insurers or their workplace. This protection does not extend to 
disability or life insurance. A current or prior cancer diagnosis is likely to be the most significant factor 
affecting life insurance, or rates and eligibility for other forms of insurance. Genetic testing 
information is unlikely to change this risk. 
 
5.3.2 
Definition of Adverse Events (AE) 
An AE is any untoward medical occurrence in a patient or clinical study subject administered a 
medicinal product and which does not necessarily have a causal relationship with this treatment. An 
adverse event can therefore be any unfavourable and unintended sign (e.g. an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal product, whether or 
not considered related to the medicinal product. 
The term AE is used to include both serious and non-serious AEs. 
 
5.3.3 
Definition of Serious Adverse Events (SAE) 
A serious adverse event is an AE occurring during any study phase (i.e., run-in, treatment, washout, 
follow-up), that fulfils one or more of the following criteria: 
• 
Results in death 

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• 
Is life-threatening (life-threatening in this context refers to a reaction in which the patient was at 
risk of death at the time of the reaction; it does not refer to a reaction that hypothetically might 
have caused death if more severe) 
• 
Requires in-patient hospitalisation or prolongation of existing hospitalisation 
• 
Results in persistent or significant disability or incapacity 
• 
Is a congenital abnormality/birth defect 
• 
Is an important medical event that may jeopardise the subject or may require intervention to 
prevent one of the outcomes listed above. Medical and scientific judgement should be exercised in 
deciding whether other situations should be considered an SAE. 
Any suspected transmission via a medicinal product of an infectious agent is also considered an SAE 
and may be subject to expedited reporting requirements in some countries. Any organism, virus or 
infectious particle (for example Prion Protein Transmitting Transmissible Spongiform 
Encephalopathy), pathogenic or non-pathogenic, is considered an infectious agent. 
It is important to distinguish between serious and severe AEs. Severity is a measure of 
intensity whereas seriousness is defined by the criteria in Sections 6.3.2. An AE of severe 
intensity need not necessarily be considered serious.  For example, nausea that persists for 
several hours may be considered severe nausea, but not a SAE unless it meets one of the 
criteria shown in Section 6.3.2. On the other hand, a stroke that results in only a limited degree 
of disability may be considered a mild stroke but would be a SAE if it satisfies one of the 
criteria shown in Section 6.3.2. 
 
  
5.3.4 
Reporting of Adverse Events 
For studies with a primary data source 
The Investigators or other site personnel will inform the appropriate AstraZeneca 
representatives within one day i.e., immediately but no later than 24 hours of when he or she 
becomes aware of: 
• All AEs with a fatal outcome 
• All serious ADRs  
 
The designated AstraZeneca representative works with the Investigator to ensure that all the 
necessary information is provided to the AstraZeneca Patient Safety data entry site within 1 
calendar day of initial receipt for fatal and life threatening events and within 5 calendar 
days of initial receipt for all other serious ADRs.  
 
For all collected AEs, where important or relevant information is missing, active follow-up is 
undertaken immediately.  Investigators or other site personnel inform AstraZeneca 
representatives of any follow-up information within the same timeframe as the original report.  

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All collected adverse events will be summarized in the final study report. 

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Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 
1975-2016, National Cancer Institute, 2018. 
2. Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, et al. Inherited DNA-
Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med. 
2016;375(5):443-53. 
3. National Comprehensive Cancer Network. Prostate Cancer (Version 4.2019). 
<https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf>. 
4. Giri VN, Knudsen KE, Kelly WK, et al. Role of Genetic Testing for Inherited Prostate Cancer 
Risk: Philadelphia Prostate Cancer Consensus Conference 2017. J Clin Oncol. 
2018;36(4):414–424.  
5. Sanda, Martin G., et al. "Clinically Localized Prostate Cancer: Aua/Astro/Suo Guideline. Part 
Ii: Recommended Approaches and Details of Specific Care Options." Journal of Urology 
199.4 (2018): 990-97. 
6. Maiese, Deborah R et al. “Current conditions in medical genetics practice.” Genetics in 
medicine : official journal of the American College of Medical Genetics vol. 21,8 (2019): 
1874-1877. 
7. Hoskovec, Jennifer M., et al. "Projecting the Supply and Demand for Certified Genetic 
Counselors: A Workforce Study." Journal of Genetic Counseling 27.1 (2018): 16-20. 
8. Bellcross, Cecelia A., et al. "Awareness and Utilization of Brca1/2 Testing among U.S. 
Primary Care Physicians." American Journal of Preventive Medicine 40.1 (2011): 61-66. 
9. Plon, Sharon E et al. “Genetic testing and cancer risk management recommendations by 
physicians for at-risk relatives.” Genetics in medicine : official journal of the American 
College of Medical Genetics vol. 13,2 (2011): 148-54.  
10. Cohen, Stephanie A., et al. "Genetic Counseling and Testing in a Community Setting: Quality, 
Access, and Efficiency." American Society of Clinical Oncology Educational Book.39 (2019): 
e34-e44. 
11. Sandu, S., Husain, M., et al. Annals of Oncology (2019) 30 (suppl_9): ix183-ix202.  
 

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6. 
APPENDICES 
Appendix A: Patient Survey on Germline Testing in Prostate Cancer 
 
Participant Name:  
_________________________________________________________ 
 
Participant Study ID:  _________________________________________________________ 
 
Date:  _____________________________________________________________________ 
 
The purpose of this section is to understand what you know generally about inherited cancer 
risk (genetic risk that occurs within a family). By understanding what you may or may not 
know about inherited cancer risk it may help us to improve our educational sessions. 
 
Below we have listed some general questions about genetics and multi-gene panel testing (a 
genetic test that evaluates more than one gene). These questions are not specific to you or your 
risk but rather common questions about genetic risk. 
 
Section A:  
Please answer these questions as True or False.  
 
 
 
True 
False 
1.  
Genes are made from pieces of DNA  
 
 
2.  
A mutation is a change in DNA sequence  
 
 
3. 
Cancer is caused by a combination of inheritance, environmental 
exposure, and lifestyle factors 
 
 
4.  
Most people who develop cancer do so because they have inherited 
risk for cancer that they were born with. 
 
 
5.  
All of the gene mutations that could increase risk for cancer have been 
discovered. 
 
 
 
 
Section B 
Please answer these questions with agree, disagree, of if you are unsure, “I don’t know”.  
 
 
 
Agree 
Disagree 
I don’t 
know 
1.  
My doctor has talked to me about genetic testing 
for my prostate cancer prior to enrolling in this 
study.  
 
 
 
2.  
Some men with prostate cancer were born with 
genetic mutations which contributed to their 
development of cancer.  
 
 
 

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3.  
Knowing about inherited risk (passed down within 
a family) can affect choices about cancer 
treatments (for example, medications or surgery). 
 
 
 
4.  
People with an inherited risk for cancer (and their 
at- risk relatives) are more likely to develop more 
than one type of cancer. 
 
 
 
5. 
The blood relatives (for example, sister, father, or 
child) of a person with a mutation in a cancer risk 
gene might share the same gene mutation. 
 
 
 
6. 
A person with an inherited risk for cancer may 
have distant relatives (for example, cousins) who 
also have increased cancer risk. 
 
 
 
7.  
All children of a person with inherited cancer risk 
will also have inherited cancer risk.  
 
 
 
 
Section C 
 
The following questions are about the extent of your interest in genetic testing for your cancer. 
1. How interested are you in undergoing genetic testing to determine if you were born with 
any genetic mutations which predisposed you to developing prostate cancer? 
A. Very interested 
B. Interested 
C. Neutral 
D. Not interested  
E. Not at all interested 
 
2. Of the following listed factors, which would most influence you in a decision to pursue 
germline DNA testing in the care of your cancer? (Rank answers in orders of preference 
from 1 to 5, 1= best describes, 5= least describes) 
 
 
 
Rank  
(1 = best, 5= least) 
Potential to guide treatment selection 
 
Potential to predict disease outcome 
 
Potential to learn more about my cancer risk 
 
Potential to learn more about the cancer risk of my family 
 
Trust in my physician and their recommendation for genetic testing 
 
 
Other (please specify; not required) 
_____________________________________________________ 
 

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3. Of the following listed factors, which would most influence you in a decision to not 
pursue genetic DNA testing in the care of your cancer? (Rank answers in orders of 
preference from 1 to 5, 1= best describes, 5= least describes) 
 
4. At the start of this educational session, my current decision on pursuing genetic testing 
is:  
A) I want to proceed with germline testing done today. 
B) I do not want to proceed with germline testing today. 
C) I am unsure at this time.  
 
 
 
 
 
 
 
 
 
Rank  
(1 = best, 5= worst) 
Potential of DNA test results to be of no clinical value 
 
 
Potential of DNA test results to lead to health, life or disability insurance 
discrimination 
 
 
Concerns about the privacy and confidentiality of DNA test results  
 
Concerns about the impact a positive result would have on my family and 
relatives. 
 
Other (please specify; not required) 
_____________________________________________________ 
 

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Appendix B: Family History Questionnaire  
 
Patient Name:  
   
Medical Record # 
 
 
Family History Questionnaire 
                  
Part 1: Personal history information 
 
 
Have you had any genetic testing of your tumor tissue?   
Yes 
  No  
 Not sure 
 
(examples: Foundation, Guardant, Tempus, or Caris testing)  
 
 
Heath history/ancestry: 
 
Ancestry (e.g. Swedish, Japanese, English)  
Mother’s side:
  
Father’s side: 
 
Any Ashkenazi Jewish Ancestry?   Yes ☐No☐ What side of the family? 
 
 
 
 
Ever had a colonoscopy? 
Yes   ☐No  ☐   If yes, any history of colon polyps?  
 
 
Other health issues you’d like to share
 
 
 
Have you had genetic counseling because of your family history of cancer before?       Yes  ☐    No   ☐    
Not sure ☐ 
 
If so, where was the genetics consultation done?  
UCSD ☐  Elsewhere: 
 
 
 
Genetic Testing History 
 
Have you ever had genetic testing for cancer risk before? 
 
Yes  ☐No  ☐  Not Sure  ☐ 

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If yes, please describe (what test, what year completed if known)  
 
 
 
What were the results?  
 
 
 
☐A mutation was found in the 
gene 
(Important: Please bring copies of results) 
 
☐No mutations were found 
 
 
 
 
 
☐My results were “uncertain” in the 
 gene  
 
 
 
 
 
☐I’m not sure 
 
Please describe any other genetic testing findings or issues: 
-
Have any of your relatives had cancer genetic testing? 
 
Yes  ☐   No    ☐  Not Sure  
☐ 
 
If yes, please describe which relative(s) and their results, if know (Important: If possible, please bring 
copies of reports) 
 
 
Part 2. Your children: 
 
How many children (living and deceased)?       
 
Please list your sons and daughters on the rows below (if you need more rows, please use the back of 
this form): 
Relative 
Ever 
diagnosed 
with 
cancer? 
Check if 
deceased 
Current 
age/ 
Age at 
death  
Cancer Type 
Age at 
diagnosis 
Son ☐ Daughter ☐ Y ☐N ☐ 
☐ 
 
 
 
Son ☐ Daughter ☐ Y ☐N ☐ 
☐ 
 
 
 
Son ☐ Daughter ☐ Y ☐N ☐ 
☐ 
 
 
 

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Part 3. Your brothers and sisters: 
How many brothers and sisters (living and deceased)?   
  
 
 Please list your brothers and sisters on the rows below (if you need more rows, please use the back of 
this form) 
 
 
Part 4. Your mother’s side of the family: 
Son ☐ Daughter ☐ Y ☐N ☐ 
☐ 
 
 
 
Son ☐ Daughter ☐ Y ☐N ☐ 
☐ 
 
 
 
Son ☐ Daughter ☐ 
Y ☐N ☐ 
☐ 
 
 
 
Relative 
Ever 
diagnosed 
with 
cancer? 
Check if 
deceased 
Current 
age/ 
Age at 
death  
Cancer Type 
Age at 
diagnosis 
Brother ☐ Sister ☐ Y ☐N ☐ ☐ 
 
 
 
Brother ☐ Sister ☐ Y ☐N ☐ ☐ 
 
 
 
Brother ☐ Sister ☐ Y ☐N ☐ ☐ 
 
 
 
Brother ☐ Sister ☐ Y ☐N ☐ ☐ 
 
 
 
Brother ☐ Sister ☐ Y ☐N ☐ ☐ 
 
 
 
Brother ☐ Sister ☐ Y ☐N ☐ ☐ 
 
 
 
Brother ☐ Sister ☐ 
Y ☐N ☐ 
☐ 
 
 
 
Relative 
Ever 
diagnosed 
with 
cancer? 
Check if 
deceased 
Current age 
or 
Age at 
death  
Cancer Type 
Age at 
diagnosis 

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How many aunts and uncles (living and deceased) on your mother’s side?        
 
Please list all of you your aunts and uncles (mother’s side) on the rows below (if you need more rows, 
please use the back of this form): 
 
 
 
Part 5. Your father’s side of the family: 
Mother 
Y ☐N ☐ 
☐ 
 
 
 
Maternal 
grandmother 
Y ☐N ☐ 
☐ 
 
 
 
Maternal 
Grandfather  
Y ☐N ☐ 
☐ 
 
 
 
Relative 
Ever 
diagnosed 
with 
cancer? 
Check if 
deceased 
Current 
age/ 
Age at 
death  
Cancer Type 
Age at 
diagnosis 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ ☐ 
 
 
 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ ☐ 
 
 
 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ ☐ 
 
 
 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ ☐ 
 
 
 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ ☐ 
 
 
 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ ☐ 
 
 
 
Relative 
Ever 
diagnosed 
with cancer? 
Check if 
deceased 
Current age 
or 
Age at death  
Cancer Type 
Age at diagnosis 
Father 
Y ☐N ☐ 
☐ 
 
 
 

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How many aunts and uncles (living and deceased) on your father’s side?       
Please list your aunts and uncles (father’s side) on the rows below (if you need more rows, please use 
the back of this form): 
 
 
 
Paternal 
grandmother 
Y ☐N ☐ 
☐ 
 
 
 
Paternal 
Grandfather  
Y ☐N ☐ 
☐ 
 
 
 
Relative 
Ever 
diagnosed 
with cancer? 
Check if 
deceased 
Current 
age/ 
Age at 
death  
Cancer Type 
Age at diagnosis 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ 
☐ 
 
 
 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ 
☐ 
 
 
 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ 
☐ 
 
 
 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ 
☐ 
 
 
 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ 
☐ 
 
 
 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ 
☐ 
 
 
 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ 
☐ 
 
 
 
Aunt ☐ Uncle ☐ 
Y ☐N ☐ 
☐ 
 
 
 

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Appendix C: Patient Post-Education Patient Survey 
 
Participant Name:  
_________________________________________________________ 
Participant Study ID:  _________________________________________________________ 
Date:  _____________________________________________________________________ 
Thank you again for taking part in our educational intervention. Before the session is over, we 
hope to get your feedback on the session so that we can continue to improve on our education 
of patients on germline testing.  
 
Section A:  
Please answer these questions as True or False.  
 
 
 
True 
False 
1.  
Genes are made from pieces of DNA  
 
 
2.  
A mutation is a change in DNA sequence  
 
 
3. 
Cancer is caused by a combination of inheritance, environmental 
exposure, and lifestyle factors 
 
 
4.  
Most people who develop cancer do so because they have inherited 
risk for cancer that they were born with. 
 
 
5.  
All of the gene mutations that could increase risk for cancer have been 
discovered. 
 
 
 
 
Section B 
Please answer these questions with agree, disagree, of if you are unsure, “I don’t know”.  
 
 
 
Agree 
Disagree 
I don’t 
know 
1.  
Some men with prostate cancer were born with 
genetic mutations which contributed to their 
development of cancer.  
 
 
 
2.  
Knowing about inherited risk (passed down within 
a family) can affect choices about cancer 
treatments (for example, medications or surgery). 
 
 
 
3.  
People with an inherited risk for cancer (and their 
at- risk relatives) are more likely to develop more 
than one type of cancer. 
 
 
 
4.  
The blood relatives (for example, sister, father, or 
child) of a person with a mutation in a cancer risk 
gene might share the same gene mutation. 
 
 
 
5. 
A person with an inherited risk for cancer may 
have distant relatives (for example, cousins) who 
also have increased cancer risk. 
 
 
 

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6. 
All children of a person with inherited cancer risk 
will also have inherited cancer risk.  
 
 
 
 
Section C 
 
The following questions are about the extent of your interest in genetic testing for your cancer. 
1. How interested are you in undergoing genetic testing to determine if you were born 
with any genetic mutations which predisposed you to developing prostate cancer? 
F. Very interested 
G. Interested 
H. Neutral 
I. Not interested  
J. Not at all interested 
 
2. Of the following listed factors, which would most influence you in a decision to pursue 
germline DNA testing in the care of your cancer? (Rank answers in orders of preference 
from 1 to 5, 1= best describes, 5= least describes) 
 
 
3. Of the following listed factors, which would most influence you in a decision to not 
pursue genetic DNA testing in the care of your cancer? (Rank answers in orders of 
preference from 1 to 5, 1= best describes, 5= least describes) 
 
Rank  
(1 = best, 5= least) 
Potential to guide treatment selection 
 
Potential to predict disease outcome 
 
Potential to learn more about my cancer risk 
 
Potential to learn more about the cancer risk of my family 
 
Trust in my physician and their recommendation for genetic testing 
 
 
Other (please specify; not required) 
_____________________________________________________ 
 
 
Rank  
(1 = best, 5= worst) 
Potential of DNA test results to be of no clinical value 
 
 
Potential of DNA test results to lead to health, life or disability insurance 
discrimination 
 
 

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Section D 
For each statement, please select if you ‘Disagree Strongly’, ‘Disagree’, ‘Neither Agree or 
Disagree’, ‘Agree’ or ‘Agree Strongly’.  
 
 
Disagree 
strongly 
Disagree 
Neither 
Agree or 
Disagree 
Agree 
Agree 
Strongly 
1. The information presented in this 
session was informative.  
 
 
 
 
 
2. The information presented in the 
session was confusing or 
difficult to understand. 
 
 
 
 
 
3. The information presented in the 
session was distressing. 
 
 
 
 
 
4. The information presented in the 
session was useful. 
 
 
 
 
 
5. The information presented in the 
session answered all of my 
questions and concerns. 
 
 
 
 
 
6. The session was the right length 
of time.  
 
 
 
 
 
1. The pamphlet was helpful in 
explaining the concept of genetic 
testing.  
 
 
 
 
 
2. For question #6, if you answered disagree to disagree strongly, please tell us whether 
your education session was:  
A) Too long 
B) Too short 
3. For question #7, if you answered disagree to disagree strongly, please tell us whether the 
pamphlet was: 
Concerns about the privacy and confidentiality of DNA test results  
 
Concerns about the impact a positive result would have on my family and 
relatives. 
 
Other (please specify; not required) 
_____________________________________________________ 
 

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A)  Too basic 
B) Too advanced 
C) Other (please specify): _________________________ 
4. At the end of this educational session, my decision on pursuing genetic testing is:  
A) I want to proceed with germline testing done today. 
B) I do not want to proceed with germline testing today. 
C) I would like to see a genetic counsellor to discuss this further.  
D) I am unsure and will decide at a later date.  
 
If you have any other comments about the educational intervention, please feel free to share 
below: 
 
___________________________________________________________________ 
___________________________________________________________________ 
___________________________________________________________________ 
___________________________________________________________________ 
___________________________________________________________________ 
 
 
 
 
 
 
 
 
 
 
 

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Appendix D: Post Results Clinician Questionnaire  
Clinician Name: ______________________________ Date: __________________________ 
Patient/Patient Study ID: ______________________________________________________ 
 
1. Did you find the germline test result helpful in the management of this patient?  
A) Yes 
B) No 
C) Unsure 
 
2. Did the results of germline testing change your management of this patient currently? 
A) Yes 
B) No 
C) Unsure 
 
3. Will the results of the testing change your management of this patient in the future? 
A) Yes 
B) No 
C) Unsure 
 
4. Did the results of this testing change your perception of the patient’s prognosis? 
A) Yes 
B) No 
C) Unsure 
 
5. Did the results of this testing lead to further diagnostic testing or referrals? 
A) Yes 
B) No 
C) Unsure 
 

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6. If you have any additional feedback about the results or educational intervention with 
regards to this patient’s case, please feel free to share:  

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Appendix E: List of genes tested with commercial germline assays 
 
Ambry Panel 
1. ATM 
2. BRCA1 
3. BRCA2 
4. CHEK2 
5. EPCAM 
6. HOXB13 
7. MLH1 
8. MSH2 
9. MSH6 
10. NBN 
11. PALB2 
12. PMS2 
13. RAD51D 
14. TP53 
 
Invitae Panel 
1. ATM  
2. BRCA1  
3. BRCA2 
4. BRIP1  
5. CHEK2  
6. EPCAM  
7. FANCA 
8. GEN1 
9. HOXB13  
10. MLH1  
11. MSH2  
12. MSH6  
13. NBN 
14. PALB2 
15. PMS2  
16. RAD51C  
17. RAD51D   
18. TP53   

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ATTACHMENTS 
 
See attached file of educational brochure brochure. 

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7. 
SIGNATURES  
Authoring Instructions 
ο 
The following signature pages for an Observational Study protocol may be required and 
further details on who is required to sign can be found in the SOP 8-P102-CV-C Design, 
Execution, and Reporting of AstraZeneca Sponsored Observational Studies : 
ο 
Global Medical Affairs Lead or Global Clinical Lead/Delegate for global studies  
ο 
MC Medical Director/Delegate for local studies 
ο 
Global Epidemiologist /Local Study Leader 
ο 
Optional signature from Biostatistician or Delivery Director 
ο 
Always print the names and addresses. 
ASTRAZENECA SIGNATURE(S) 
<<Study Description>> 
<<This Observational Study Protocol >> <<has/have>> been subjected to an internal 
AstraZeneca review>> 
I agree to the terms of this Study protocol. 
AstraZeneca representative 
<<Name, title>> 
<<Email address and telephone 
number>> 
Date 
(Day Month Year) 
This document contains confidential information, which should not be copied, referred to, 
released or published without written approval from AstraZeneca.  Investigators are cautioned 
that the information in this protocol may be subject to change and revision.