A Phase II Randomized Controlled Trial of Exercise in Prostate Cancer Patients Undergoing Active Surveillance
Phase: NA
Conditions: Prostate Cancer
Sponsor: University of Alberta

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Exercise during Active Surveillance for Prostate Cancer: 
The ERASE Trial 
 
Version: 2.2 
Creation/Revision Date: July 16, 2018 
Clinical Trial Registration: NCT03203460 
 
Short Title 
The ERASE Trial 
Sponsor 
Alberta Health Services, Cross Cancer Institute 
Principal investigator 
Kerry S. Courneya, PhD  
Professor and Canada Research Chair in Physical 
Activity and Cancer 
Director, Behavioural Medicine Laboratory 
Faculty 
of 
Physical 
Education 
and 
Recreation, 
University of Alberta 
Other investigators 
Catherine J. Fields, PhD  
Professor of Nutrition 
Associate Editor Advances in Nutrition 
Department of Agricultural, Food and Nutritional 
Science, University of Alberta 
 
Normand G. Boulé, PhD 
Professor & Associate Dean (Graduate) 
Faculty 
of 
Physical 
Education 
and 
Recreation, 
University of Alberta 
 
Dong-Woo Kang, MSc 
PhD Candidate 
Behavioural Medicine Laboratory 
Faculty 
of 
Physical 
Education 
and 
Recreation, 
University of Alberta 
Trial Site 
University of Alberta, Edmonton, AB, Canada 
T6G 2H9 
780-492-1031 
Qualified physician, who 
is responsible for all 
trial-site related medical 
decisions (if other than 
investigator).  
Name: Adrian S. Fairey, MD 
Affiliation: Urological Surgeon & Assistant Professor, 
Division of Urology, Department of Surgery. Faculty of 
Medicine & Dentistry, University of Alberta 
Address: Northern Alberta Urology Centre 
7th Floor, Kaye Edmonton Clinic, 11400 University 
Avenue, Edmonton, AB, Canada T6G 1Z1 
Phone: 780-407-5800 (ext. 3) 

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Clinical laboratories and 
other medical and/or 
technical 
departments 
and/or 
institutions 
involved in the trial.  
Name: Norther Alberta Urology Centre 
Address: 7th Floor, Kaye Edmonton Clinic, 11400 
University Avenue, Edmonton, AB T6G 1Z1 
 
Name: Human Nutrition Research Group (Biochemical 
Assays) 
Address: 4031 Li Ka Shing Center, Edmonton, AB T6G 
2E1 
 
Name: Behavioural Medicine Fitness Centre 
Address: 1-001 Research Transition Facility, 8308-114 
St., Edmonton, AB T6G 2H9 
 
Name: Behavioural Medicine Fitness Testing room 
Address: 
1-661 
Cross 
Cancer 
Institute, 
11560 
University Ave, Edmonton, AB T6G 1Z2 

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1 Study Summary/ Synopsis 
Title 
Exercise during Active Surveillance for Prostate Cancer 
Short Title 
The ERASE Trial 
Protocol Number 
- 
Phase 
Phase 2  
Methodology 
Randomized, usual care control, two-armed, parallel design 
Study Duration 
18 months (January 2018 – June 2019) 
Study Center(s) 
Single-center 
Objectives 
To examine the effects of exercise in prostate patients 
undergoing active surveillance 
Number of Subjects 66 
Accrual rate and 
Justification 
Considering >1,500 potentially eligible patients in the 
registry and approximately 10 new patients placed on active 
surveillance per month, this project will require only a 4% 
response rate to achieve our targeted sample size. 
Diagnosis and Main 
Inclusion Criteria 
Prostate cancer patients initiating or continuing active 
surveillance with no plans for treatment for prostate cancer 
in the next 6 months 
Investigational 
product, treatment 
or intervention  
A structured exercise program – Supervised high-intensity 
interval aerobic exercise, 3 sessions/week, 30 minutes per 
session 
Duration 
of 
administration 
12 weeks 
Reference therapy 
Usual care group – Standard active surveillance protocol (no 
structured exercise program) 
Statistical 
Methodology 
ANCOVA – To detect differences between-group changes 
before and after the exercise intervention 

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2 Table of Contents 
1 
Study Summary/ Synopsis ......................................................................................................... 3 
2 
Table of Contents ........................................................................................................................... 4 
3 
Introduction .................................................................................................................................... 6 
3.1 
Background and Rationale ................................................................................................. 6 
3.2 
Compliance Statement ......................................................................................................... 9 
3.3 
Description of the population to be studied ............................................................ 10 
3.4 
Trial Objectives and Purpose ......................................................................................... 10 
3.5 
Trial Design ........................................................................................................................... 10 
3.6 
Trial Endpoints .................................................................................................................... 10 
3.7 
Steps to Minimize Bias ..................................................................................................... 11 
3.8 
Trial Treatment ................................................................................................................... 11 
3.9 
Trial Duration ...................................................................................................................... 11 
3.10 
Discontinuation Criteria .............................................................................................. 11 
3.11 
Source Data ....................................................................................................................... 12 
4 
Methodology: Participants, Interventions and Outcomes .......................................... 12 
4.1 
Consent ................................................................................................................................... 12 
4.2 
Eligibility Criteria ............................................................................................................... 12 
4.3 
Sample Size ........................................................................................................................... 13 
4.4 
Recruitment .......................................................................................................................... 14 
4.5 
Interventions ........................................................................................................................ 14 
4.6 
Outcomes ............................................................................................................................... 16 
5 
Methodology: Data Collection, Management, and Analysis ....................................... 18 
5.1 
Data Collection Methods .................................................................................................. 18 
5.2 
Statistics ................................................................................................................................. 18 
5.3 
Criteria for the Termination of the Trial ................................................................... 19 
5.4 
Deviations .............................................................................................................................. 19 
5.5 
Analysis .................................................................................................................................. 19 
5.6 
Data Management .............................................................................................................. 20 
6 
Quality Control, Quality Assurance and Monitoring ..................................................... 20 
6.1 
Direct Access to Source Data/Documents ................................................................ 20 
6.2 
Data Monitoring .................................................................................................................. 21 

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6.3 
Auditing .................................................................................................................................. 22 
7 
Approvals ...................................................................................................................................... 23 
7.1 
Ethics ....................................................................................................................................... 23 
7.2 
Operational Approvals ..................................................................................................... 23 
8 
Protocol Amendments .............................................................................................................. 23 
9 
Protocol Registration ................................................................................................................ 23 
10 Publication Policy ....................................................................................................................... 24 
11 References ..................................................................................................................................... 24 
12 Appendices .................................................................................................................................... 31 
12.1 
Appendix – Figure 2. Proposed Flow Diagram of the ERASE Trial ............. 31 
12.2 
Appendix – Figure 3. High-intensity interval training (HIIT) Exercise 
Program in the ERASE trial. ........................................................................................................ 32 
12.3 
Appendix – List of Abbreviations ............................................................................. 34 
12.4 
Informed Consent Materials ...................................................................................... 34 
12.5 
Data Collection Tools ........................................ Error! Bookmark not defined. 
12.6 
Biological Specimens .................................................................................................... 35 
 
 

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3 Introduction 
3.1 Background and Rationale  
Prostate cancer (PCa) is the most common cancer in Canadian men with over 
21,000 new cases diagnosed each year1. Conventionally, a PCa diagnosis is treated 
immediately by radical prostatectomy, radiation therapy, and/or hormonal therapy2. 
These treatments improve overall survival; however, they also are expensive and 
often cause serious side effects such as sexual and urinary dysfunction, fatigue, loss 
of lean body mass, muscle weakness, and poor quality of life3,4. Consequently, there is 
a desire to only offer these radical treatments to men who will obtain a clear clinical 
benefit. In recent years, a subset of men with PCa have been identified who have a 
very low risk of disease progression and death from PCa. These men are unlikely to 
obtain a clear clinical benefit from immediate radical treatments. To address this 
issue, a clinical practice called “active surveillance (AS)” has emerged and is being 
offered to men with low-to-moderate grade PCa. In AS, men with low risk PCa do not 
receive any immediate treatments but are monitored closely for any signs of tumour 
growth. Curative medical treatments are offered only if the disease progresses5. The 
obvious advantage of AS is that it allows early-stage PCa patients to avoid treatment-
related side effects without compromising their survival6. Moreover, AS represents a 
considerable cost savings over radical treatment7-9, estimated at $96.1 million per 
year in Canada10. Due to these advantages, the number of PCa patients being offered 
AS in Canada has increased substantially11. 
Unfortunately, many men with PCa on AS will eventually experience disease 
progression and require radical treatments. Approximately 30% of men on AS will 
have radical treatments within three years and about 55% will have treatment within 
10 years. Moreover, even if these men do not experience an objective progression of 
their disease, they may experience a fear of cancer progression based on the fact they 
have an untreated tumor with a high chance of progressing12. Fear of cancer 
progression and uncertainty of illness are associated with anxiety and poor quality of 
life in AS patients13 and may even prompt these men and their doctors to opt for 
radical treatments as a way of managing the fear and anxiety14. Cost-effective 
interventions that can slow tumor progression, manage fear of cancer 
progression, and prepare PCa patients on AS for impending radical treatments 
would be highly beneficial. To date, however, no such interventions are offered as 
standard of care in this clinical setting. 
 
Lifestyle Interventions in Prostate Cancer Patients on Active Surveillance 
One promising line of inquiry is examining the potential role of lifestyle 
interventions in men with PCa on AS. For example, one study investigated the effects 
of a year-long intensive lifestyle program on PCa progression and health-related 
quality of life in 92 PCa patients on AS (Prostate Cancer Lifestyle Trial, PCLT)15,16. The 
intervention was comprised of a vegan diet, moderate-intensity aerobic exercise 
(walking 30 minutes per day for 6 days per week), stress management, and a weekly 
1-hour support group session17. At 3 months, an interim analysis only for the 
intervention group showed significant improvements in cardiovascular risk factors 

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such as body mass index, abdominal obesity, blood pressure, and lipid profile as well 
as several indicators of psychological functioning including mental component 
summary, intrusive thoughts, and avoidance18. Total and free prostate-specific 
antigen (PSA) levels were not significantly improved although the percentage of free 
PSA showed a non-significant but clinically meaningful change18. After one year of 
intervention, in addition to similar improvements in cardiovascular risk factors, total 
PSA was significantly reduced by 4% in the intervention group while it increased by 
6% in the control group15. Also, the growth of LNCaP PCa cells, androgen-sensitive 
human prostate adenocarcinoma cells, was inhibited 8-times more in the 
intervention group compared to the control group15. Moreover, overall health-related 
quality of life increased in the intervention group compared to the control group 
although no significant differences were found in other subscales such as physical- 
and mental-health, perceived stress, and sexual function16. After 2 years of follow-up 
for clinical events, they reported that 2 of 43 (5%) patients in the intervention group 
and 13 of 49 (27%) patients in the control group had proceeded to radical PCa 
treatments (prostatectomy, radiotherapy, or hormone therapy), while no significant 
differences in PSA levels and the number of other clinical events were found19. After 
5 years of follow-up, telomere length increased in the intervention group and 
decreased in the control group while PSA and telomerase activity were not 
significantly different between groups20. Overall, this study provided promising 
evidence that an intensive lifestyle intervention in PCa patients on AS may slow the 
progression of the disease, improve some aspects of quality of life, and decrease the 
rate of radical treatments. 
Another randomized controlled trial in 26 men with PCa undergoing AS tested 
the effects of a six-month combined whole-grain diet and vigorous exercise 
program21. The exercise program included non-supervised aerobic exercise three 
times/week for 45 minutes/session targeting 70% of maximal heart rate (HR) in 
addition to at least 10,000 steps daily. The combined intervention resulted in an 
improvement in peak oxygen consumption (VO2peak) in the intervention group 
compared to the control group, however, no other significant differences were found 
for body composition, cardiometabolic outcomes, or PSA after six months of 
intervention.  
Another intervention study with 40 overweight or obese men with PCa 
provided a presurgical weight loss intervention consisting of diet and physical 
activity22; however, only feasibility outcomes have been reported and the focus of the 
study is on men electing radical prostatectomy. Several other cohort, cross-sectional, 
and systematic review studies have also concluded that lifestyle interventions are a 
promising avenue of research for improving tumor outcomes in PCa patients on AS23-
25. As might be expected, however, these early preliminary studies have limitations 
including few randomized controlled trials, small sample sizes, unsupervised exercise 
interventions, and the testing of packaged lifestyle interventions that do not allow the 
disentangling of the key active components of the intervention. 
 
Exercise is one of the key components of a lifestyle intervention that may have 
independent effects on clinical outcomes in PCa patients on AS; however, no study to 
date has tested the effects of an isolated exercise intervention. Exercise has been 
shown to delay the progression of prostate tumors in animal models26-28, which is 

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mainly attributed to alterations in immune function29; however, these findings have 
not been confirmed in men with PCa. Moreover, exercise has been shown to improve 
health-related fitness30-33, physical functioning31-37, body composition31-34,37, 
fatigue32-34,36, and quality of life32-34,36,38 during and after radical PCa treatments, but 
no study to date has focused on the AS setting or examined fear of cancer progression 
– the psychological construct most likely to result in unnecessary medical 
intervention. Furthermore, exercise may help prepare PCa patients for radical 
treatments (i.e., prehabilitation)39-41 but current studies are only preliminary and 
none have focused on PCa patients on AS. Our novel idea is that exercise may be a 
cost-effective intervention that slows the growth of PCa tumors and manages 
fear of cancer progression, thereby allowing these men to remain on AS longer 
or even indefinitely. Moreover, exercise may help buffer the negative effects of 
radical treatments in the >50% of men who will ultimately require medical 
treatments. 
 
Theoretical Model (Figure 1) 
We propose that exercise—sufficient to improve cardiorespiratory fitness 
may benefit men with PCa on AS through three distinct pathways: (1) In the 
“biological pathway”, exercise may have a direct effect on suppressing tumour growth 
thereby delaying or preventing the need for radical treatments in AS patients. 
Scientific evidence shows that exercise can modulate cancer-related circulating 
markers in various mechanisms42-44 such as immune function45-48 (e.g., natural killer 
(NK) cell mobilization and infiltration into cancer cells), metabolism49,50 (e.g., insulin 
and insulin-like growth factor(IGF)-axis), and inflammation51 (e.g., interleukin-6(IL-
6) from myokines, tumour necrosis factor (TNF)-α, high-sensitive c-reactive 
protein(hs-CRP)), which creates an anti-tumour microenvironment, resulting in a 
delay or even reversing of tumour progression29. (2) In the “psychological pathway”, 
exercise may reduce the fear of cancer progression through several psychological 
mechanisms such as providing a distraction and a sense of control, reducing 
anxiety/cancer worry and intrusive thoughts, and providing an alternative 
explanation for everyday symptoms such as mild pain, fatigue, and soreness that may 
be misinterpreted as signs of cancer progression12,13. These psychological benefits 
may also improve quality of life and prevent these men from requesting radical 
treatments as a way of managing their anxiety and fear of cancer progression. (3) In 
the “functional pathway”, exercise can improve patients overall physical function and 
condition such as aerobic fitness, muscular strength, body composition, and activities 
of daily living. Improvements in these factors may help reduce the impact and 
complications of radical treatments. If PCa patients on AS feel they are better 
prepared physically for radical treatments and will experience fewer side effects and 
complications, they may also reduce their fear of cancer progression. In summary, 
we propose that exercise in PCa patients on AS may suppress tumour 
progression and reduce fear of cancer progression which may help these men 
remain on AS longer. A longer time on AS would mean improved survival and 
quality of life for these men and lower financial costs for society. 
 

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Figure 1. Proposed Effects of Exercise during Active Surveillance in Prostate 
Cancer Patients 
 
 
Principles Guiding the Selection of the Exercise Training Intervention 
In terms of maximizing the potential benefits of exercise in AS patients, a body 
of evidence supports that higher-intensity exercise programs often produce greater 
health benefits compared to moderate-intensity continuous training52,53. High-
intensity interval training (HIIT) aerobic exercise is a type of high-intensity exercise, 
alternating short periods of intense exercise and active recovery. HIIT has been 
shown to induce better outcomes such as cardiopulmonary fitness and 
cardiovascular disease (CVD) risk factors in patients with heart disease, compared to 
traditional moderate-intensity exercise53-56. Moreover, HIIT is not only feasible and 
safe in several types of cancer patients but also beneficial in improving physical 
fitness and mental health57-60. Finally, given that higher-intensity exercise may be 
required to induce a sufficient increase in NK cell infiltration to kill tumour cells (up 
to 60% in animal models), it is plausible that HIIT may be the optimal intervention 
for boosting cancer surveillance and tumor suppression in AS patients29,61. 
3.2 Compliance Statement 
This trial will be conducted in compliance with the protocol, GCP and the 
applicable regulatory requirement(s). 

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3.3 Description of the population to be studied  
The population to be studied in the ERASE Trial will be men with PCa initiating 
or continuing AS. These patients are men diagnosed with low- or favorable 
intermediate grade localized PCa. These patients do not receive immediate PCa 
treatment, but visit the clinic for regular check-ups, typically every three months for 
PSA and DRE and every 18 months for prostate biopsy, until the PCa becomes 
significant where treatment is necessary.  
3.4 Trial Objectives and Purpose  
The overall goal of the Exercise during Active Surveillance for Prostate Cancer 
(ERASE) Trial is to examine the effects of exercise in PCa patients undergoing AS. The 
primary objective is to examine the effects of HIIT on VO2peak in PCa patients 
undergoing AS. The secondary objectives are to examine the effects of HIIT on: (1) 
other health-related fitness outcomes including physical function and body 
composition, (2) tumor-related serum biomarkers including immune, metabolic, and 
inflammatory markers, and (3) patient-reported outcomes including fear of cancer 
progression, quality of life, and symptoms. The exploratory objectives are to examine 
the effects of HIIT on indicators of cancer progression including tumour volume and 
PSA levels. 
3.5 Trial Design  
The ERASE Trial will be a prospective, single center, two-armed, phase II 
randomized controlled trial at the University of Alberta, Cross Cancer Institute (CCI), 
and Northern Alberta Urology Centre (NAUC) in Edmonton, Alberta. Ethics approval 
will be obtained from the Health Research Ethics Board of Alberta-Cancer Committee 
(HREBA-CC) prior to commencing the trial. 
3.6 Trial Endpoints 
3.6.1 Primary Endpoints 
The primary endpoint of the ERASE trial is VO2peak. 
3.6.2 Secondary Endpoints 
The secondary endpoints are (1) tumour-related immune, metabolic, and 
inflammatory biomarkers, (2) patient-reported fear of cancer progression, quality of 
life, anxiety, depression, fatigue, perceived stress, self-esteem, and PCa-specific 
symptoms, (3) physical function, and (4) body composition.  
3.6.3 Exploratory Endpoints 
The exploratory endpoints are tumour progression outcomes using PSA, DRE, 
and endo-rectal multiparametric magnetic resonance imaging (MP-MRI). 

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3.7 Steps to Minimize Bias 
Participants will be randomly assigned to either the exercise group or the 
usual care group in a 1:1 ratio after baseline assessment. The randomization scheme 
will include stratification for the length of time on AS (<6 months versus ≥6 months) 
and variable block sizes of 4 to 8. The allocation sequence will be produced by 
computer-generated random numbers and concealed from staff involved in 
recruitment and baseline testing. Given the nature of the exercise intervention, it is 
not possible to blind participants and interventionists to group allocation. Outcome 
assessors, however, will be blinded to group allocation for the primary outcome of 
VO2peak and the secondary/exploratory outcomes of physical function, body 
composition, biomarker assays, and tumour progression. The assessors will also 
follow the detailed protocol to minimize any potential bias in measurements. 
3.8 Trial Treatment 
The treatment group will be provided a 12-week, supervised, HIIT aerobic 
exercise program. The type of exercise will consist of alternating vigorous and low 
intensity interval running or walking performed on a treadmill. Exercise sessions will 
be provided three times per week and each session will last approximately 30 
minutes. The intensity of exercise will be determined by treadmill speed and/or 
incline and will be prescribed and gradually increased at specific workloads 
corresponding to percentage of VO2peak measured at baseline. An exercise session of 
1) warm-up (5 min at a workload corresponding to 65% of VO2peak), 2) high-intensity 
exercise phase (2 min at an increasing workload corresponding to VO2peak at 85% in 
the 1st -4th week, 90% in the 5th -8th week, and 95% in the 9th-12th week) followed 
by recovery phase (2 min at a workload corresponding to 35-45% of VO2peak), 3) four 
more sets of high-intensity exercise and recovery phases adding 1 additional interval 
every 4 weeks, and 4) cool-down (5 min at a workload corresponding to 40% of 
VO2peak). For the purpose of quantifying exercise intensity, patient-reported exertion 
levels will be recorded using the Borg’s Rating of Perceived Exertion Scale and HR will 
continuously be monitored using a HR monitor at the end of each interval.  
3.9 Trial Duration 
The expected participant flow in the ERASE Trial is illustrated in the Appendix 
– Figure 2. In brief, after randomization, participants will be provided with an 
exercise intervention for 12 weeks and then receive postintervention assessment and 
long-term follow-ups for exercise behaviour at 6 and 12 months. 
3.10 Discontinuation Criteria 
Discontinuation criteria include (1) receiving any invasive PCa treatment 
during the 12-week intervention period due to tumour progression, patients’ 
preference, and/or any reasons determined by referred oncologists, and (2) any 
intolerable adverse event or intercurrent illness associated or not associated with the 
study intervention and/or assessment, where patients are considered to be unable to 
continue participating in the intervention. 

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3.11 Source Data 
Patients’ medical information will be abstracted from the NAUC patient 
registry, including tumor-related information, complications or comorbidities. Ethics 
approval from the HREBA-CC will be obtained for the acquisition of the patient data 
from the registry. Demographic and behavioral information will be obtained using a 
self-report questionnaire at baseline. The questionnaire will ask age, ethnicity, 
education, marital status, income, employment status, smoking, and alcohol 
consumption.  
 
 
4 Methodology: Participants, Interventions and Outcomes 
4.1 Consent 
All patients will be informed about 
• The aims of the study 
• The possible adverse events 
• The procedures and possible hazards to which the patient will be exposed 
• The mechanism of treatment allocation 
• Strict confidentiality of any patient data 
• Medical records possibly being reviewed for trial purposes by authorized 
individuals other than their treating physician 
The consent is given as a separate document dated and version controlled to 
this protocol. The informed consent documents are to be completed based on the 
template provided from the HREBA-CC and submitted to the ethics committee for 
approval. It is emphasized in the patient information sheet that participation is 
voluntary and that the patient is free to refuse further participation in the protocol 
whenever he wants to and this will not have any impact on the patient’s subsequent 
care. Documented informed consent will be obtained for all patients included in the 
study. The written informed consent form will be signed and personally dated by the 
patient or by the patient’s legally acceptable representative.  
4.2 Eligibility Criteria 
4.2.1 Inclusion Criteria  
Men will be eligible for the trial if they (1) are ≥ 18 years old, (2) diagnosed 
with low or favorable intermediate grade localized PCa defined as PSA less than 10, 
Gleason Score 3+3 or 3+4 with low volume, and digital rectal examination (DRE) of 
T1C or T2A, (3) initiating or continuing AS with no plans for treatment in the next 6 
months, (4) receive medical clearance to perform maximal aerobic exercise testing 
and HIIT as determined by their treating urologist, the Physical Activity Readiness 
Questionnaire, and a Certified Exercise Physiologist, and (5) willingness to attend a 

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12-week supervised exercise training program at the University of Alberta or 
continue with their usual activity. 
4.2.2 Exclusion Criteria  
Patients will be excluded if they (1) have any plans for treatment in the next 6 
months, (2) have any uncontrolled medical conditions that could be exacerbated with 
HIIT, (3) have contraindications for cardiopulmonary stress and/or physical fitness, 
and/or (4) are currently exercising defined as >0 minutes of vigorous intensity 
exercise and >150 minutes of moderate intensity exercise in a typical week over the 
past month. 
4.2.3 Withdrawal Criteria 
Withdrawal criteria include: (1) patient’s self-withdrawal to permanently 
discontinue study treatment and withdraw from the study anytime for any reason, 
and following study intervention discontinuation, patients will have protocol-
required safety and long-term follow-up assessments unless the patient specifically 
declines further follow-up), 2) having any invasive PCa treatment and/or any 
intolerable adverse event associated or not associated with the study intervention 
and/or assessment, and 3) gross noncompliance with protocol where the investigator 
requests permanent discontinuation of the study intervention in the event of a major 
protocol deviation, lack of cooperation, or complete noncompliance). 
Participants are free to withdraw from the trial at any stage without providing 
a reason and without consequence. This information will be stated in the consent 
document. Participants can inform the research team at their local site of their 
decision to withdraw. If a participant withdraws from the study, any data collected 
on him up to that point in the study will go forward for study analysis. This 
information will be stated in the participant information leaflet. If a participant 
withdraws from the intervention, but provides consent to complete subsequent 
follow-up measurements he will continue to attend study assessments and data will 
be used for intention-to-treat analysis. Reasons for stopping the intervention will be 
recorded and reported. 
4.3  Sample Size 
4.3.1 Sample Size Calculation 
A sample size of 60 participants (30 per group) provides 80% power using a 
two-tailed alpha <0.05 to detect a clinically meaningful increase of a 1 metabolic 
equivalent task (MET = 3.5 ml/kg/min) on our primary outcome of VO2peak assuming 
a standard deviation of 5.6 ml/kg/min and adjustment for baseline value and other 
prognostic covariates62. An increment of a 1 MET in cardiopulmonary fitness, 
equivalent to approximately 1km/h higher running/jogging speed, is shown to 
correspond to an improvement of 13% and 15% in overall and CVD-related survival, 
respectively63. Considering a potential drop-out rate of <10% based on our previous 
exercise oncology trials64-67, a total of 66 participants (33 per group) will be 
randomized. This power will also be sufficient for detecting differences in our 

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secondary biomarkers and patient-reported outcomes if the effects are moderate (i.e., 
a standardized effect size of approximately ≥ d=0.60). This power is not sufficient for 
detecting potentially meaningful differences in any of the exploratory clinical 
outcomes. Given that the purpose of this phase II trial is to inform phase III trials, the 
patient-reported and clinical outcomes will also be interpreted for potential clinical 
significance based on the direction and magnitude of numerical differences. For our 
main patient-reported outcome of interest—QoL assessed by the QLQ-C30—we will 
judge a clinically meaningful effect to be a between-group difference of 10 points68. 
For our primary clinical outcome of interest—progression to radical treatment—we 
will judge a clinically meaningful effect to be a between group absolute difference of 
10%. 
4.3.2 Accrual Period  
The target accrual number is 66 and we expect to recruit this targeted number 
of patients over 8 months (March – August 2018). Recruitment will be through the 
NAUC at the Kaye Edmonton Clinic. Currently, the NAUC has more than 1,500 PCa 
patients on AS in the registry and typically puts approximately 10 new patients on AS per 
month. We will mail out an invitation to the study and interested patients will contact our 
research team. 
We have used this mailed invitation approach to recruit to previous 
randomized supervised exercise trials and were able to recruit 53 of 370 (14%) 
breast cancer survivors65, 22 of 324 (7%) lymphoma survivors66, 30 of 502 (6%) PCa 
survivors64, and 63 of 948 (7%) testicular cancer survivors69. To achieve our targeted 
sample size of 66 in the ERASE trial will require only a 4% response rate from the 
1,500 PCa patients on AS currently in the registry. 
4.4 Recruitment  
Recruitment will be through the NAUC at the Kaye Edmonton Clinic, 
Edmonton, Canada. Patients will be screened for eligibility through the patient 
registry and eligible patients will be informed about the study by their physicians and 
research staff or from the study recruitment poster displayed at the patient waiting 
room during their check-up visits. All interested patients will receive details of the 
study from the study coordinator and further screened for current physical activity 
readiness and participation level. Those patients who are eligible and agree to 
participate will then be asked to provide informed consent and schedule a baseline 
assessment. 
4.5 Interventions 
4.5.1 Treatment 
Exercise Group 
Patients randomized to the exercise group will be provided with standard AS 
care and asked to complete a 12-week, supervised HIIT program in addition to any 
moderate intensity exercise they were previously doing (Appendix - Figure 3; HIIT 
Protocol). The type of exercise will consist of alternating vigorous- and low-intensity 

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intervals performed on a treadmill. The intensity of exercise will be modified by 
changing treadmill speed and/or grade prescribed at specific workloads 
corresponding to percentage of VO2peak measured at baseline. Exercise frequency will 
be three times per week and each session will last approximately 30 minutes. The 
detailed exercise program consists of 1) warm-up (5 min at a workload 
corresponding to 65% of VO2peak), 2) high-intensity exercise phase (2 min at an 
increasing workload corresponding to VO2peak at 85% in the 1st -4th week, 90% in the 
5th -8th week, and 95% in the 9th-12th week) followed by recovery phase (2 min at a 
workload corresponding to 35-45% of VO2peak), 3) four more sets of high-intensity 
exercise and recovery phases adding 1 additional interval every 4 weeks, and 4) cool-
down (5 min at a workload corresponding to 40% of VO2peak)54,55. For the purpose of 
quantifying exercise intensity, patient-reported exertion levels will be recorded using 
the Borg’s Rating of Perceived Exertion Scale70 and HR will continuously be 
monitored using a HR monitor (Polar U.S., Woodbudy, NY) at the end of each interval. 
We have recently tested this HIIT protocol in testicular cancer survivors and found 
large improvements in VO2peak and cardiovascular risk factors69. 
 
Usual Care Group 
Patients randomized to the usual care group will be provided with standard 
AS care. Currently, the standard AS care at our site does not include any formal 
exercise program or recommendation. Consequently, participants in the usual care 
group will be asked not to initiate any vigorous intensity exercise program or to 
increase their moderate intensity exercise from baseline during the 12 week study. 
After the post-intervention assessments, patients in the usual care group will be 
offered a 4 week supervised exercise program at our facility or referred to a 12 week 
community-based program called the Alberta Cancer Exercise (ACE) program. 
 
After the 12-week study period, participants in both exercise and usual care 
groups will be followed up at 6 and 12 months for their exercise behaviour assessed 
using a modified version of the Godin Leisure-Time Exercise Questionnaire71. 
4.5.2 Study Calendar 
 
Before 
Treatment 
(Baseline) 
Post- 
Treatment 
(At 12-week) 
Follow-up 
1 
(At 6-month) 
Follow-up 
2 
(At 1-year) 
Consent 
X 
 
 
 
Medical History & Information 
X 
 
 
 
Demographics 
X 
 
 
 
Treatment (HIIT) 
X 
 
 
Cardiorespiratory Fitness Test 
X 
X 
 
 
Tumour-related Biomarkers Test 
X 
X 
 
 
Physical Function Test 
X 
X 
 
 
Body Composition Test 
X 
X 
 
 
QOL and Psychosocial Questionnaires 
X 
X 
X 
X 
Tumour Progression  
X 
X 
X 
X 

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Before 
Treatment 
(Baseline) 
Post- 
Treatment 
(At 12-week) 
Follow-up 
1 
(At 6-month) 
Follow-up 
2 
(At 1-year) 
Exercise Behaviour 
X 
X 
X 
X 
4.5.3 Medications/Treatments Permitted 
Patients will not have any medication-, diet-, and/or supplement-related 
restriction before and/or during the trial.  
4.5.4 Monitoring Compliance 
During the 12-week intervention period, exercise adherence to the prescribed 
exercise program will be monitored and recorded based on attendance at the 
scheduled exercise sessions and completion of the intensity, duration, and number of 
intervals during each exercise session. Strategies to maximize adherence will include 
appointment-based sessions, flexible scheduling, individualized exercise program, 
supervision by certified clinical exercise physiologists, free parking, and use of the 
Behavioural Medicine Fitness Centre (BMFC) which is available only to cancer 
patients participating in clinical exercise trials. Any missed sessions will trigger a 
telephone call with a rescheduling of the exercise session as soon as possible. Using 
these strategies, we have achieved high exercise adherence rates in previous 
supervised exercise trials including 98% in breast cancer survivors65, 79% in PCa 
patients on androgen deprivation therapy36, 92% in lymphoma survivors66, 88% in 
PCa patients receiving radiation therapy33, 98% in PCa survivors64, and 99% in 
testicular cancer survivors69. 
4.6 Outcomes 
4.6.1 Primary Outcomes 
The primary outcome of this phase II trial is cardiorespiratory fitness, which 
is a powerful surrogate for cancer-specific and overall survival. Cardiorespiratory 
fitness will be assessed as VO2peak by a peak exercise stress test using the modified 
Bruce exercise protocol72. Participants will be provided with detailed and verbal 
instruction about the procedure of the test and asked for abstaining from smoking, 
alcohol, and caffeine within 3 hours, and exercise within 24 hours prior to the test. 
Resting HR, blood pressure (BP), and health conditions will be measured before the 
test to stabilize resting metabolic values. After the warm-up (1.7 – 2.5 mph; 0% grade; 
5 minutes) followed by 5 minutes rest, the test starts at 0% grade and a 1.7 mph 
walking pace and will progress every 3 minutes until the patient reaches volitional 
exhaustion or any exercise contraindications occur. During the test, oxygen uptake 
and HR will be measured continuously. VO2peak is defined as the highest oxygen-
uptake value recorded during the test and will be quantified where participants reach 
a plateau in oxygen consumption, respiratory exchange ratio of 1.1 or above, or 9 to 
10 on the modified Borg rated perceived exertion73. After the test, HR will be 
measured for an additional 6 minutes of recovery (1st minute marching in place plus 

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5 minutes of active recovery). VO2peak will be expressed relative to body mass (ml 
O2·kg-1·min-1; primary) and absolute terms (litres/min). 
4.6.2 Secondary Outcomes 
Circulating biomarker outcomes 
Fasting blood will be taken in the morning following an overnight fast where 
there was no food intake after 8pm and a minimum of 48 hours since the last vigorous 
exercise session. Blood draws can occur on the same day as the exercise assessment, 
prior to the commencement of the assessments. Serum blood will be drawn in the 
6.0mL red top tube, clotted for 30-60minutes, and spun for 20 minutes at 2860 rpm. 
Then, 0.75mL of serum will be transferred to each of the four cryovials provided. Two 
10.0 mL EDTA tubes will be collected and one spun for 10 minutes at 2860 rpm within 
one hour of collection and 1.0mL of plasma will be transferred to a secondary tube to 
cryovials. The remaining blood from the second tube will be centrifuged and on Ficoll 
gradients and the peripheral blood mononuclear cells (PBMC) Ficoll isolated74 and 
frozen in RPMI 1640 media containing 20% FCS and 10% DSMO and stored in liquid 
nitrogen. Samples will be stored or shipped frozen at -70°C and the Biological Sample 
Log will be completed. Frozen PBMC will be warmed in a 37 oC water bath for 3 
minutes, in media and incubated overnight at 37 oC in the presence of 5% CO74 and 
then used to identify NK cells (CD3-CD16+CD56+) using flowcytometry and to 
measure NK activity using a flow cytometry method75 that has been validated for 
previously frozen PBMC. This assay incubates K562 cells with 2 × 105 effector cells 
(NK cells) and measures CD107a expression which correlates with the release of 
perforin and other cytolytic granules that induce death of tumour cells. Metabolic 
biomarkers, including serum insulin, glucose, IGF-1, IGFBP-3, and adiponectin, will be 
assessed using the ELISA kits on frozen samples. Inflammatory markers will include 
proinflammatory cytokines such as IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, 
IL-13, TNF-α, and hs-CRP, assessed using a multi-ligand analysis system according to 
commercial kit instructions on frozen plasma or serum. 
 
Patient-reported outcomes 
1) Fear of cancer progression will be assessed using the 8-item Cancer Worry 
Scale76 and the 9-item Fear of Cancer Recurrence Inventory77. 2) Quality of life will be 
assessed using the 30-item European Organization for Research and Treatment of 
Cancer- Quality of Life Questionnaire-C3078. 3) PCa-specific health-related quality of 
life and symptoms including urinary incontinence, sexual dysfunction, and bowel 
dysfunction will be assessed using the 26-item Expanded Prostate Cancer Index 
Composite-2679. 4) General anxiety and prostate-specific anxiety will be assessed 
using the 10-item Spielberger State-Trait Anxiety Inventory80 and the 18-item 
Memorial Anxiety Scale for Prostate Cancer81, respectively. 5) Depression will be 
measured using the 10-item Center for Epidemiologic Studies Depression Scale82. 6) 
Fatigue will be assessed using the 13-item Functional Assessment of Cancer Therapy- 
Fatigue83. 7) Perceived stress will be assessed using the 14-item Perceived Stress 
Scale84. 8) Self-esteem will be assessed using the 10-item Rosenberg Self-Esteem 
Scale85. 719) Motivation to exercise will be assessed based on the Theory of Planned 

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Page 18 of 35 
Behaviour constructs (instrumental and affective attitudes, subjective norms, 
intention and perceived control)86. 
 
Physical function 
Physical function will be assessed using the Senior’s Fitness Test87 which 
includes lower body strength (chair stand), upper body strength (arm curl), lower 
body flexibility (chair sit and reach), back scratch (upper body flexibility), and 8-foot 
up and go (agility) tests.  
 
Anthropometric measurements 
Height, body weight, and waist and hip circumferences will be measured using 
height and weight scales and a tape measure, respectively. 
4.6.3 Exploratory Outcomes 
Tumor progression outcomes 
Tumour progression will be assessed using PSA and DRE. Total PSA will be 
measured by two-site automated immunoluminometric assays on Liason (sandwich 
principle) (Byk-Sangtec Diagnostica, Dietzenbach, Germany). Both assays, calibrated 
to the Stamey Reference Standard, will employ two different but highly specific 
monoclonal antibodies for coating of the solid phase (magnetic particles) and for the 
tracer. The concentration of the antigen in the samples will be measured in relative 
light units by way of the chemiluminescence reaction induced and the light signal 
produced, which is directly proportional to the antigen concentration. Mean intra- 
and inter-assay coefficient of variations of the assays is lower than 8.0 %. DRE will be 
conducted by the physician inserting a gloved, lubricated finger into the rectum and 
examining the prostate for any irregularities in size, shape, and texture.  
 
 
5 Methodology: Data Collection, Management, and Analysis 
5.1 Data Collection Methods 
5.1.1 Case Report Forms (CRFs) 
Patient data related to the study will be recorded on the CRFs. Patients will not 
be identified by name on the CRFs or any study documents, but will be identified by 
participant ID numbers. If a correction is required for a CRF, the time and date marks 
track the person entering or updating CRF data. 
5.2 Statistics 
5.2.1 Description of Statistics 
Analyses of covariance will be performed to compare the between-group 
differences at post-intervention after adjustment for the baseline value of the 
outcome and potential covariates. All statistical analyses will include all patients with 

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Page 19 of 35 
baseline and follow-up data and will be conducted based on the intention-to-treat 
principle. If missing data is <10% as expected we will conduct a complete case 
analysis. If missing data is >10%, we will employ a multiple imputation missing data 
strategy88. 
5.2.2 Level of Significance to be used 
All analyses will be considered statistically significant with a 2-tailed α=0.05. 
5.3 Criteria for the Termination of the Trial  
The investigator has the right to close their study at any time. The sponsor 
(Alberta Health Service-CCI) has the right to close this study (or, if applicable 
individual segments thereof [e.g. treatment arms, centers]) at any time, which may be 
due but not limited to the following reasons: 
5.3.1 Futility 
If the study conduct (e.g. recruitment rate, drop-out rate, data quality, protocol 
compliance) does not suggest a proper completion of the study within a 
reasonable time frame the trial will be terminated. 
5.3.2 Safety 
If risk-benefit ratio becomes unacceptable owing to, for example,  
• Safety findings from this study (e.g. SAEs);  
• Results of parallel clinical studies 
• Results of parallel animal studies (e.g. toxicity, teratogenicity, 
carcinogenicity or reproduction toxicity). 
For any of the above closures, the following applies: 
• Closures should occur only after consultation between involved parties. 
• All affected institutions (e.g. HREBA-CC; competent authorities; study centers) 
must be informed as applicable according to local law. 
• All study materials (except documentation that has to remain stored at site) must 
be returned to the sponsor. The investigator will retain all other documents until 
notification given by the sponsor for destruction. 
• In case of a partial study closure, ongoing subjects, including those in post study 
follow-up, must be taken care of in an ethical manner] 
5.4 Deviations  
Given that we will strictly follow the statistical plan as described in the 
protocol, we do not expect that there will be any deviations from the original 
statistical plan. 
5.5 Analysis  
All subjects who are randomized will be included in the analyses using the 
intention-to-treat analysis approach. There will be no interim analyses. 

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5.6 Data Management 
5.6.1 Data Accounting  
All missing, unused, or spurious data will be cross checked between 
researchers who are in charge of data management. If missing data is <10% as expected 
we will conduct a complete case analysis. If missing data is >10%, we will employ a 
multiple imputation missing data strategy88 
5.6.2 Confidentiality of Trial Documents and Patient Records 
Data collection forms will contain names, initials, date of birth, and study ID 
numbers. These are for filing and data entering purposes only and all data entered 
and analyzed will use study ID numbers. All data will be entered into a database on a 
password-protected computer. Only the research team members will have access to 
the password. Interpretation of the results will be in group data format and 
participants will not be identified. 
5.6.3 Retention of Patient Records and Study Files 
All data will be securely stored in accordance with Tri-Council and University 
guidelines. Following data analysis, identity records will be destroyed and identifiers 
will be removed from the data. At the University of Alberta, researchers are required 
to keep data for 5-years following the publication of data. The data will be anonymous 
and stored in a locked office for 1-2 years post completion of study during 
preparation of manuscripts. After publication, the data will be stored in a locked 
storage facility managed by the Faculty of Physical Education and Recreation at the 
University of Alberta. Good Clinical Practice Guidelines and Health Canada and FDA 
regulations state that clinical trial records must be maintained for 25 years, and thus 
the data from this trial will be stored in a locked storage facility managed by the 
Faculty of Physical Education and Recreation at the University of Alberta. Following 
the 25 year time period, the data will be destroyed by shredding which will be 
overseen by the Behavioral Medicine Lab. Electronic copies will also be destroyed at 
this point in time. 
 
 
6 Quality Control, Quality Assurance and Monitoring 
6.1 Direct Access to Source Data/Documents 
Clinical trial audits are performed to provide assurance that the rights, safety 
and wellbeing of patients are properly protected, to assess compliance with the 
protocol, processes and agreements, ICH GCP standards and applicable regulatory 
requirements, and to assess the quality of data. 
The investigator will permit trial-related monitoring, audits, HREBA-CC, and 
regulatory inspections, providing direct access to paper and/or electronic 
documentation pertaining to the clinical study (e.g. CRFs, source documents such as 

PROJECT PROTOCOL 
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Page 21 of 35 
hospital patient charts and investigator study files). All site facilities related to the 
study conduct could be visited during an audit. The investigator agrees to co-operate 
and provide assistance at reasonable times and places with respect to any auditing 
activity. 
6.2 Data Monitoring 
6.2.1 Efficacy/Safety 
6.2.1.1 Assessment of Efficacy 
6.2.1.1.1 Efficacy Parameters  
Efficacy of the study will be determined by a 1-MET (3.5 ml/kg/min) 
difference of between group changes in the primary outcome of VO2peak. The 
secondary outcomes of psychosocial distress, biological parameters, physical 
function, body composition, and tumour progression variables will also be considered 
to determine the efficacy of the study. 
6.2.1.1.2 Methods and timing for assessing, recording, and analyzing of efficacy 
parameters.  
The methods for assessing the efficacy parameters are described in detail in 
the 4.6. Outcomes. The timing of assessments for efficacy parameters will be 
conducted at baseline, postintervention (at 12-week), the first follow-up (at 6-
month), and the second follow-up (at 1-year) and detailed timing of assessment for 
each parameter are described in 4.5.2. Study Calendar. 
6.2.1.2 Assessment of Safety 
6.2.1.2.1 Safety Parameters 
For assessment of safety for the HIIT intervention, symptom-limited 
cardiopulmonary exercise test during the screening period will be conducted. Vital 
signs or any physical symptoms and concomitant medications will be continuously 
obtained during and after every exercise intervention sessions.  
Adverse event(AE)s will be assessed at every clinic visit and the following 
details recorded on the case report form, including type, severity, relationship to 
exercise intervention, expectedness, timing, action taken (if any) and outcome. In this 
trial, the study intervention is a supervised high-intensity interval aerobic exercise 
program. All potential participants will be screened via their medical charts as well 
as through in-person assessments to assess cardiovascular and functional 
contraindications to exercise. Our multi-gated comprehensive approach should 
systematically identify and screen out any individual for whom this study is 
contraindicated.  
Absolute indications for stopping exercise (both testing and training) are: 1) 
suspicion of a myocardial infarction or acute myocardial infarction (heart attack), 2) 
onset of moderate-to-severe angina (chest pain), 3) drop in systolic blood pressure 

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(SBP) below standing resting pressure or drop in SBP with increasing workload 
accompanied by signs or symptoms or hypotensive response resulting in SBP 
<60mmHg, 4) signs of poor perfusion (circulation or blood flow) including pallor 
(pale appearance to the skin), cyanosis (bluish discoloration) or cold and clammy 
skin, 5) severe or unusual shortness of breath, 6) central nervous system symptoms, 
including ataxia, vertigo, visual or gait problems, and/or confusion, 7) irregular pulse, 
8) extreme fatigue, 9) skeletal fracture, and/or 10) patient’s request to stop. Relative 
indications include: 1) increasing chest pain, 2) physical or verbal manifestations of 
shortness of breath or severe fatigue, 3), wheezing, 4) leg cramps or intermittent 
claudication (grade 3 on a 4-point scale), and/or 5) hypertensive response. 
6.2.1.2.2 Reporting and Recording Adverse Events 
All AEs and serious AE(SAE)s reported by the patient, discovered during 
questioning, directly observed, or detected by physical examination, laboratory test 
or other means will be immediately recorded in the patient’s medical record and on 
the AE form. All AEs will be reviewed by the principal investigator. The investigator 
is responsible for notifying the HREBA-CC about AEs. 
6.2.1.2.3 Follow up of Adverse Events 
Return to exercise following reporting of an adverse event which requires 
updated physician clearance will be discussed on a case by case basis. Where 
physician clearance to return to exercise is deemed necessary, the participant will 
only be allowed to return to exercise training when physician clearance is provided 
in writing. The exercise physiologist supervising the exercise program will modify the 
program accordingly at re-introduction. If no physician clearance is deemed 
necessary the participant can return to training upon clearance from the exercise 
physiologist. 
6.2.1.2.4 Analysis of Safety and Adverse Events 
Adverse event rates will be summarised with frequency and percentage within 
each arm and across arms. Rates between groups will be compared using the 
intention-to-treat approach. In addition, AE incidence rates will be summarized by 
severity and relationship to the intervention. Intervention-related AEs are those 
judged by the Investigator to be at least possibly related to the intervention. Adverse 
events with missing severity or relationship to the intervention will be classified as 
severe and treatment-related, respectively. Patients with multiple occurrences of 
events will only be counted once at the maximum severity for each preferred term, 
SOC, and overall. 
6.3 Auditing 
Given that this trial is a single site study of an exercise intervention, no 
auditing/monitoring independent from the investigators is planned. 
 
 

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7 Approvals 
7.1 Ethics 
We ensure that the ERASE Trial will be submitted to the HREBA-CC for the 
study protocol, informed consent form, and any informational materials given to the 
patient or used to recruit patients. 
7.1.1 Patient Protection 
The responsible investigator will ensure that this study is conducted in 
agreement with the Declaration of Helsinki. The protocol has been written, and the 
study will be conducted according to the ICH Harmonized Tripartite Guideline on 
Good Clinical Practice. The HREBA-CC must approve the protocol, informed consent 
form and any trial materials given to participants. 
7.1.2 Subject Identification 
A sequential identification number will be automatically allocated to each 
patient registered in the trial. This number will identify the patient and will be 
included on all CRFs. 
7.2 Operational Approvals 
This study will be conducted at the Behavioral Medicine Laboratory (BML), 
the Behavioral Medicine Exercise Testing Facility (BMET), BMFC, the NAUC, and the 
immune assay lab. The principal investigator, Dr. Courneya, directs BML, BMET, and 
BMFC, which no further operational approvals will be necessary. The operational 
approvals have been obtained for the NAUC via the co-investigator, Dr. Adrian Fairey, 
and the GU Tumour Board and for the biochemical assay lab via its director and the 
co-investigator, Dr. Catherine Field. 
 
 
8 Protocol Amendments 
All amendments to the protocol (e.g., changes to eligibility criteria, outcomes, 
and analyses) must undergo review by the HREBA-CC. Amendments will be circulated 
to all participating investigators in a standard format with clear instructions 
regarding the HREBA-CC review. 
 
 
9 Protocol Registration  
The information regarding this trial has been made publicly available on the 
internet at www.clinicaltrials.gov with the trial registration number of 
NCT03203460. 
 
 

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10 Publication Policy  
The publication of the main trial results will be written by the Principal 
Investigator on the basis of the final analysis and will be sent to a major scientific 
journal. Authors of the manuscript will include at least the Principal Investigator and 
any co-investigators who have i) included eligible patients in the trial (by order of 
inclusion) or ii) contributed significantly to the design, conduct and data 
interpretation regarding companion basic science studies. 
Publication or presentation of study data before the publication of the primary 
trial endpoint may be authorized at the discretion of the Principal Investigator. The 
data collected during this study are confidential. 
 
 
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12 Appendices 
12.1 Appendix – Figure 2. Proposed flow diagram of the ERASE Trial 
 
 
 

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12.2 Appendix – Figure 3. High-intensity interval training (HIIT) 
Exercise Program in the ERASE trial. 
 
 
 

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12.3 Appendix – Figure4. Potential benefits of prehabilitation across 
cancer experience 
 
 
 

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12.4 Appendix – List of Abbreviations 
Abbreviation 
Full Name 
AS 
active surveillance 
BMET 
behavioral medicine exercise testing facility 
BMFC 
behavioral medicine fitness centre 
CCI 
cross cancer institute 
CRF 
cardiorespiratory fitness 
CRF 
case report form 
HIIT 
high-intensity interval training 
HR 
heart rate 
HREBA-CC 
health research ethics board of alberta-cancer committee 
MET 
metabolic equivalent task 
MP-MRI 
endo-rectal multiparametric magnetic resonance imaging 
NAUC 
northern alberta urology centre 
PBMC 
peripheral blood mononuclear cells 
PCa 
prostate cancer 
PSA 
prostate-specific antigen 
(S)AE 
(serious) adverse event 
VO2peak 
peak oxygen consumption 
 
 

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12.5 Appendix – Biological Specimens 
Fasting blood will be taken in the morning following an overnight fast where 
there was no food intake after 8pm and a minimum of 48 hours since the last vigorous 
exercise session. Blood draws can occur on the same day as the exercise assessment, 
prior to the commencement of the assessments. Gloves must be worn at all times 
when handling specimens. Tubes, needles, and pipets must be properly disposed of 
in biohazard containers, in accordance with institutional requirements. A vacutainer 
and a 23 Gauge needle is recommended for collection. Freezers need to have an alarm 
monitoring system and a backup generator or other emergency system in place. 
Samples will be stored in our -80○C monitored and alarmed freezer that only 
the research team will have access to it. Security codes are needed to get into the hall 
and then another set of security codes are needed to get into the room where the 
freezer is. A Gatekeeper Security System NU-1540 has been installed on the freezer. 
The Gatekeeper is an electronic keypad lock with a motor driven latch. The built-in, 
non-volatile memory stores an audit trail. The freezer is located in the Li Ka Shing 
building at the University of Alberta. 
Anticipated uses of collected specimen: 
• Collection of sample for immediate use: local analysis of prostate cancer-
specific antigen, lipid profile, fasting glucose, HbA1c, CBCD, natural killer cell 
assay, proinflammatory cytokines. 
• Collection of sample for banking (future use): Blood collected at baseline and 
post-intervention for banking. 
• Analysis of banked samples: Baseline and post-intervention samples will be 
used for the analysis from the banked centres. 
Specimens will be used to determine whether biomarkers of inflammation, energy 
metabolism, and androgen metabolism are associated with tumour progression 
among prostate cancer patients undergoing active surveillance, and explore the 
extent to which these biomarkers mediate the hypothesized association between 
high-intensity interval training and tumour progression.