EXERCISING TOGETHER © for Couples Coping With Cancer
Phase: NA
Conditions: Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Breast Carcinoma, Colorectal Carcinoma, Malignant Solid Neoplasm, Prostate Carcinoma, Stage I Colorectal Cancer AJCC v8, Stage I Prostate Cancer AJCC v8, Stage II Colorectal Cancer AJCC v8, Stage II Prostate Cancer AJCC v8, Stage III Colorectal Cancer AJCC v8, Stage III Prostate Cancer AJCC v8
Sponsor: OHSU Knight Cancer Institute

 
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Protocol Version 21.0 – 05/17/2024 
OHSU Knight Cancer Institute 
Minimal-risk Protocol 
 
 
Title: EXERCISING TOGETHER© for Couples Coping with Cancer 
 
 
 
Principal Investigator:     Kerri Winters-Stone, PhD 
 
 
 
       Oregon Health & Science University 
 
 
 
       SN-ORD 
 
 
 
       (503) 494-0183             
  
Co-Investigators:             Chris Lee, PhD (617) 552-1804 
 
 
 
       Karen Lyons, PhD (617) 552-6379 
 
 
 
            
  
Biostatistician:                 Nathan Dieckmann  
 
 
                  Oregon Health & Science University 
 
 
 
       SN-ORD 
 
 
 
       (503) 494-2843 
                     
  
Current Protocol Date: 
05/17/2024 
 
 
 
 

 
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Protocol Version 21.0 – 05/17/2024 
 
TABLE OF CONTENTS 
1.0 
Background/ Rationale (required)........................................................................................ 3 
2.0 
Objectives ............................................................................................................................ 4 
3.0 
Study design/Methodology (required) ................................................................................. 5 
4.0 
Study Population (required) ............................................................................................... 13 
5.0 
Inclusion/Exclusion Criteria (required) ............................................................................... 13 
6.0 
Vulnerable Populations (required) ..................................................................................... 14 
7.0 
Setting (required) ............................................................................................................... 14 
8.0 
Study Procedures and Schedule of Events (required) ...................................................... 15 
9.0 
Data and Specimens (required) ......................................................................................... 19 
10.0 Risks to Subjects (required)............................................................................................... 20 
11.0 Potential Benefits to Subjects (required) ........................................................................... 22 
12.0 Timeline & Milestones (required) ....................................................................................... 23 
13.0 Bio-statistical Considerations (if applicable) ...................................................................... 23 
14.0 Recruitment Methods (required) ........................................................................................ 25 
15.0 Informed Consent (required, unless a waiver or alteration is approved by the IRB) ........ 26 
16.0 Changes to Protocol (required, ok to use the suggested language below) ...................... 27 
17.0 Privacy, Confidentiality, and Data Security (required) ...................................................... 27 
18.0 OHSU IRB Reporting of Unanticipated Problems and Adverse Events (only if applicable)
 
28 
19.0 OHSU Knight Cancer Institute Data and Safety Monitoring Plan (only if applicable) ...... 28 
20.0 Inclusion of Women, Minorities and Children (only if applicable) ..................................... 31 
21.0 Inclusion of Children (only if applicable) ............................................................................ 33 
22.0 References (if cited above) ................................................................................................ 34 
 
 
 

 
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1.0 BACKGROUND/ RATIONALE (REQUIRED)  
 
Prostate (PC), breast (BC), and colorectal (CRC) cancer survivors account for 51% of the 
15.5 million cancer survivors in the U.S.[1] – a figure expected to grow by 10 million in less 
than a decade. Nearly all of these cancer survivors are over age 40 and are expected to live 
many years, if not decades, after their cancer diagnosis, raising concerns about the impact of 
cancer on their long-term health, work ability and health care expenses. Compared to the general 
population, cancer survivors have a higher risk of recurrence than their initial risk for cancer1, 
dying of CVD than cancer [2, 3], and reporting functional limitations and/or an inability to work [4-
8]. Cancer survivors are more likely to have multiple chronic conditions besides cancer that are 
associated with up to $13K in medical expenditures and $9K in lost productivity per survivor, per 
year [9]. Most cancer survivors are married when diagnosed and cancer will also threaten the 
physical and mental health of their aging spouse and the quality of their marital relationship - in 
effect doubling the societal and economic impact of cancer. Spouse caregivers experience 
significant health declines, such as increased CVD risk [10, 11], and are at greater risk for mobility 
limitations [12] and mortality than other family caregivers [13-19].  
Since husbands and wives typically share environments, behaviors and values the health 
and wellbeing of couples becomes closely intertwined, where the physical and mental 
health of one partner influences the others’ [20-22]. Thus, focusing solely on the survivor or 
spouse may miss a critical component of the cancer experience – i.e., the interdependent nature 
of the couple. Declining physical health of a spouse can also profoundly impact on marital quality 
[22-25] and chronic illness can rob a couple of intimacy, further straining the relationship. Recent 
evidence suggests that poor relationship quality significantly increases the risk for CVD and 
mortality [26-29], underscoring the need for novel ways to maintain or restore the supportive 
nature of the couple with cancer. Despite the threats that cancer imposes on the health of couples 
and recognition that the health of intimate partners is strongly intertwined, there are no evidence-
based strategies in practice that simultaneously address the physical, mental and relationship 
needs of this rapidly escalating demographic of the U.S. population.  
 
No singular program yet addresses the triple threat of declines in survivor and spouse 
health (physical and mental) and of their marital relationship. In the marital literature, couple-
based interventions are more effective than individual-based interventions for improving individual 
and couple outcomes [30-32], but these approaches focus on psychosocial and relational 
outcomes with no attention to physical health [33]. The physical benefits of exercise for cancer 
survivors are recognized [34], but the potential added benefit of bringing the spouse into an 
exercise program with the survivor is not. Exercise may be even more important for spouses of 
chronically ill partners than spouses of healthy couples yet to our knowledge there are just a few 
controlled trials [35] targeting caregivers, and interventions were behaviorally-focused on 
increasing participation in aerobic activities with only one including any measure (blood pressure) 
related to cardiovascular health. Prior to our work, the only exercise interventions to include the 
spouse and patient in an exercise intervention included a non-exercising spouse as a way to 
improve patient adherence to rehabilitation for osteoarthritis [36] or CVD [37]. 
 
To fill this gap, we have developed an exercise strategy where the couple trains as a team 
to create a singular approach to simultaneously improve physical, mental and relationship 
health of the couple. Exercising Together is a partnered strength training program designed to 
improve health and promote teamwork by the couple.  Our pilot study (1R21CA137272) of 
Exercising Together performed in a group of PC couples (n=64) was highly feasible (100% 
retention) and improved physical fitness, mood and affectionate behavior [38-40]. We believe 
these outcomes occurred because we fostered skills within the couple to better collaborate, 
communicate, and support one another during exercise and our conceptual model theorizes this 

 
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will lead to better physical, mental and relational health within the dyad. As a next step toward 
broader dissemination, we need to know if a couples-based exercise approach is similarly 
effective for couples coping with other cancers (and when survivor gender varies), early in the 
illness trajectory when a couple’s relationship is most vulnerable, and at reducing risk factors for 
chronic illness in both partners. An equally important next step is to distinguish the unique benefits 
of partnered training on individual and couple health from the possible benefits of exercising in a 
group with others and/or of engaging both partners in a new health behavior. We propose a larger, 
more rigorous trial of Exercising Together, expanding to include couples coping early on with PC, 
BC or CRC, clinical markers of chronic disease risk, and comparison groups that can test the 
unique benefits of partnered training. 
 
Additional background for ancillary study: Rural cancer survivors are at greater risk for a variety 
of poor health outcomes, even many years after their cancer diagnosis, but are the least likely to 
have access to programs and resources to improve their health and well-being. Improving 
health behaviors, such as physical activity, can have a substantial impact on quality of life and 
survival in cancer survivors and their partners, but rural and poor adults, and particularly cancer 
survivors, have low rates of physical activity. Survivors living in rural areas and/or in poverty 
face many barriers to exercise, particularly facility-based, supervised programs which can 
provide a more effective, safe and supportive engaging environment than unsupervised training. 
There are no studies of supervised group exercise in rural and poor cancer survivors and no 
studies at all, even distance-based programs, that target partners and the couple as a whole. 
Given our successful adaptation of Exercising Together to remote delivery during the COVID 19 
pandemic, we may be able to extend our programs to couples coping with cancer who would 
never be able to participate in our parent trial. 
2.0 OBJECTIVES 
We propose a 3-group, 12-month (6 mos. of exercise training + 6-mo. follow-up) randomized 
trial in 294 couples comparing a supervised group program of Exercising Together to: 1) separate 
supervised group exercise (survivor-only and spouse/partner-only classes) and 2) separate 
unsupervised exercise where survivors and spouses/partners exercise on their own at home. We 
hypothesize that Exercising Together will significantly improve physical, mental and relationship 
health of couples more than separate exercise performed in a group or home setting and that 
benefits will persist long-term. The study addresses the following aims: 
Aim 1: Determine the efficacy of Exercising Together on relationship quality (intimacy, 
communication and incongruence) in couples coping with PC, BC, or CRC. 
Aim 2: Determine the efficacy of Exercising Together on the physical health (body composition, 
lipids, insulin resistance, blood pressure, inflammation, and physical function) and mental health 
(anxiety, depressive symptoms, fear of recurrence) of both the survivor and spouse/partner. 
Aim 3:  Determine how long individual and couple-level benefits from Exercising Together last. 
Aim 4 (Exploratory): Identify the types of couples that benefit most from Exercising Together. 
 
Ancillary study: We have received supplemental funding to conduct a pilot study with the 
following aim: Assess the feasibility and acceptability of remotely delivered supervised, group-
based exercise to couples coping with cancer living in geographically underserved counties in 
Oregon. We will recruit an additional cohort of 30 couples (60 participants) coping with breast, 
prostate or colorectal cancer residing in five geographically underserved counties in Oregon 
(Wheeler, Malheur, Jefferson, Lake, and Benton counties). Data collected from the ancillary study 
will not be combined with data from the parent trial. Instead, data from the ancillary study will be 
compared to data collected in the parent trial to evaluate accrual, retention, and adherence rates, 
safety, intervention fidelity, and proportion of testing visits and measures completed. The ancillary 

 
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study will use separate recruitment materials, consent forms, and telephone screening scripts 
from the parent trial. 
 
3.0 STUDY DESIGN/METHODOLOGY  
The Exercising Together trial is a single-blind, parallel group, randomized trial comparing 3 
arms: Arm 1 (experimental): Exercising Together where couples perform partnered exercise in a 
supervised, group setting versus two comparator conditions where survivors and 
spouses/partners perform exercise routines separately in either a supervised group setting (Arm 
2) or unsupervised at home (Arm 3). All three arms will train for a 6-month period and then be 
followed up 6 months later. Data will be collected at baseline, 3, 6 and 12 months. 
Ancillary study: Participants who enroll in the ancillary study will not be randomized. Eligible 
couples who agree to participate in supervised exercise will be assigned to the Exercising 
Together program. Eligible couples who decline to participate will be offered the option to enroll 
in the Survivor / Spouse/Partner Home Training program. 
 
Study Arms 
All Programs: Regardless of group assignment, all participants will be expected to engage in 1-
hr exercise sessions, 2 d/wk for 6 months. For participants assigned to supervised exercise 
training, both arms will be held at the same location within a wave and in a similar block of time 
to aid in enrollment, but scheduled in a way to reduce contamination (i.e., there will be 15 minutes 
between the end of Exercising Together and the beginning of Survivor-Spouse/Partner Group 
classes. The latter are run at the same time, but in different rooms at a single location). Class size 
will be limited to 9-10 couples per class (Arm 1) or 9-10 persons in a spouse/partner or survivor 
class (Arm 2) so that enough attention is given to participants to ensure proper form and safety. 
For participants assigned to home-based training they can opt to exercise at a facility or to follow 
an instructional DVD at home (see below).  
 
Functional Strength Training: The basic training program for all three study arms is a functional 
strength training program based on recommendations for improving muscle strength in adults [41] 
and our prior studies in cancer survivors. Participants wear a weighted vest while performing lower 
body resistance exercises (chair rises, 90 squats, lunges). By wearing weighted vests, functional 
exercises can be performed without encountering balance-related safety risks from handheld 
barbells and dumbbells. Participants use free weights (dumbbells and bands) to provide overload 
for upper body exercises (1-arm row, bench press, push ups, triceps extension, shoulder raise). 
Volume of resistance exercise, determined by intensity (weight, tailored to each individual) and 
duration (number of repetitions and sets), is gradually increased from low weight and high 
repetitions to more weight and fewer repetitions over the training period for continuous overload. 
Unique features of our strength training program make it particularly suitable to be performed as 
a partnered program even among training partners who differ in their exercise capacity. We 
prescribe strength training as a relative intensity so that it can be tailored for each individual. 
Specifically, the amount of weight placed in vests for lower body exercise is prescribed as a % of 
body weight, so that untrained individuals with greater body mass, reflective of absolute lean 
mass, begin with a higher weight than smaller individuals. For upper body exercises, the 
individually determined amount of weight that a participant can lift the prescribed # of times, or 
resistance band that a participant can complete a prescribed # of repetitions correctly, will be 
used to set resistance. Other paired activities, such as dance, require that both partners exercise 
at the same absolute intensity which likely demands different levels of effort from each individual 
- creating safety concerns for the partner who is expending greater effort or undertraining partners 
who are limited by their less fit partner. The initial training progression across the study is based 
on our prior work and pilot study of Exercising Together [39, 42, 43]. Instructors, the Project 

 
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Director and Dr. Winters-Stone will confer on a monthly basis to refine individual participant efforts 
across arms based on tolerance and to adjust training progression. 
 
C.5a. Exercising Together: Participants randomized to Exercising Together will attend supervised 
classes led by two certified exercise instructor(s) who are trained by the study team. One 
instructor will focus on instructing participants on proper form and safety during training, while the 
second will focus on teaching and reinforcing the teamwork (i.e., communication and supportive 
behaviors) within the couple during exercise. Both partners will be expected to attend the same 
exercise sessions, but partners can attend separately in the event the other cannot, though we 
will discourage this except for unusual circumstances (i.e., illness). Participants attend classes 
along with other couples from the same recruitment wave to insure that progression of exercise 
is consistent among participants.  
 
Unlike group exercise where individuals perform the same exercise in synchronized fashion led 
by an exercise instructor, partnered strength training requires training partners to interact with one 
another, verbally and physically during training. In Exercising Together, the survivor and his/her 
spouse/partner will build skills to work as a team. We will foster the skills a couple uses as they 
collaborate toward a common goal (e.g., improve their health and functioning). Based on our 
conceptual model we incorporate skills that promote and reinforce  what we feel are the key 
characteristics of a successful team (communication, motivation, and support) and use this to 
guide training of couples to maximize their teamwork during each exercise session. During each 
exercise, one partner will assume the role of “trainer” and the other “exerciser” and then switch. 
We hypothesize that the teamwork skills used when training will permeate outside of the exercise 
setting and enhance the overall relationship of the couple.  The exercise instructor focusing on 
teamwork will discuss the role of training partners in the early phase of the intervention and will 
continually work with participants to develop their roles as training partners and functioning as a 
team using the principles of collaboration, communication and supportive behaviors. In addition 
to partner roles, we will build teamwork and couple interactions by having participants perform 2-
4 tandem exercises per session (i.e., lunge with ball pass, standing tandem balance). A tandem 
exercise is one where the couple must work together to complete the exercise. Tandem exercises 
require the couple to communicate and interact both non-verbally and verbally and provide a 
challenging but fun opportunity for direct interaction around exercise. We can modify tandem 
exercises if one partner is more limited than the other, yet retain the interactive element. 
Survivor / Spouse/Partner Group Training: Participants will attend separate group exercise 
classes for survivors and for spouses/partners and a certified exercise instructor will lead each 
class. The way that we structure the time and location of supervised classes will allow for the two 
trainers leading Exercising Together classes to then each lead a survivor or spouse/partner group 
class. Survivor and spouse/partner classes will be run at the same time at the same location to 
make it easier for spouses/partners who need to travel together; however, they are not required 
to do so. Each group will follow the general functional strength training program similar to our prior 
studies with BC or PC survivors only [42, 43], without any element of teamwork.  
 Participants assigned to supervised exercise may perform all exercise sessions remotely (e.g., 
at home) using videoconferencing software. The necessary exercise equipment and a webcam 
may be provided if needed, and will be returned at the end of study. Participants will receive 
written and verbal instructions for installing and using videoconferencing software. During these 
web-based, group video conferences, the exercise instructors will observe and instruct 
participants using the same format as on-site classes.  
Ancillary study: Participants enrolled in the ancillary study and assigned to Exercising Together 
will perform exercise sessions remotely as described above. 

 
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Participation in the ancillary study requires the ability to video conference with the research team. 
As needed, couples may be provided an Internet capable device with sufficient screen size to 
view the participant in a standing position (i.e., Chromebook or tablet). Devices will be collected 
when participation is complete. 
Survivor / Spouse/Partner Home Training: Participants will be given equipment (vest, weights 
and/or resistance bands) and a program to do at home or a facility, depending on their preference. 
Within two weeks of randomization, each couple will have two one-hour training sessions with an 
exercise trainer who will teach them our functional strength training program, modified to their 
abilities and for home or facility use. We will also provide them with a general DVD of the strength 
program to follow at home. The trainer will check in weekly by phone in month 1 and monthly 
thereafter to assess tolerance and modify programs as needed. We have delivered home-based 
resistance training this way in our prior studies without any related injuries [42-44]. Participants 
can perform the program on days (allowing for 48 hours between sessions) and at times 
convenient for them. There is no requirement that partners exercise at the same time, though we 
will track the degree to which couples may do so in case we need to account for this in analyses. 
Six-Month Follow-Up Period  
To evaluate the persistent effects of Exercising Together on individual and relationship health, all 
couples will be followed for an additional 6 months after formal training stops. Couples may wish 
to maintain their exercise habits or participate in shared activities other than exercise after formal 
training stops and we will not discourage them from doing so. To provide couples in supervised 
programs a resource to continue to engage in exercise after supervised training stops we will 
provide them with a DVD of their programs to use at home. During the last month of supervised 
training we will prepare participants for the transition to unsupervised training with discussions 
about behavioral strategies to stay active. We will assess participation in exercise and shared 
activities at 9 & 12 months and consider these behaviors in analysis for Aim 3 (see Analysis 
Plan). We will also repeat all measures at month 12 in order to better assess the residual effects 
of Exercising Together among couples that do or do not continue to exercise or engage in shared 
activities in the follow-up period.  
 
Participant safety. None of our participants have dropped out of a study due to an injury related 
to exercise training; however, as with any study in older adults, exercise adherence has been 
affected by minor musculoskeletal complaints that usually stem from pre-existing orthopedic 
conditions. We will reduce the risk of injury and symptoms that might limit exercise adherence by: 
1) required physician clearance for every participant and 2) monitoring and early care of 
musculoskeletal symptoms. If a survivor develops metastatic disease during the study his/her 
data from the point of the diagnosis will be considered separately, but s/he could continue in the 
study program with physician clearance. 
 
Participant Incentives: Remuneration will be provided to couples based on completion of each 
study related activity as outlined in the table below, at each of the four main time points 
(baseline, 3-months, 6-months, and 12-months).  
 
To offset travel burden for couples who live outside of the Portland metro area, a $25 
remuneration will be provided at testing visits for couples whose travel exceeds a 60-mile 
roundtrip. In addition, we will provide added compensation for excess miles driven (outside of 
the 60-mile roundtrip) using the 2020 standard mileage rate for medical visits of 17 cents per 
mile. The total travel compensation will not exceed $100 per testing time point for a maximum 
total compensation of $400 per couple. When travel exceeds 150 miles roundtrip, the couple 
may be provided with one night of hotel accommodations in the OHSU vicinity.  

 
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A couple completing only remote testing and surveys will be compensated $35 per visit, for a 
total of $140 over the course of their one year enrollment.  
 
A couple traveling less than 30 miles from OHSU and completing in-person testing, blood draw, 
and surveys will be compensated $85 ($100 with remote testing) per visit, for a total of $340-
$400 over the course of their one year enrollment.  
 
A couple traveling > 60 miles roundtrip from OHSU and completing in-person testing, blood 
draw, and surveys will be compensated between $110 and $185 depending on mileage ($125-
$200 with remote testing), for a total of $440-$800 over the course of their one year enrollment. 
 
Study Activity 
Compensation per time point*, per couple 
Surveys 
$20 
Performance testing –  remote 
$15 
Performance testing – in-person 
$25 
Blood draw 
$40 
Travel >60mi roundtrip from OHSU  
$25 + $0.17/mi outside of 30mi, max $100 
total 
Travel >150mi roundtrip from OHSU 
1 hotel night 
*Time points: baseline, 3-month, 6-month, and 12-month 
 
Ancillary study: Participants enrolled in the ancillary study will participate remotely and will not be 
asked to travel, therefore they will not receive remuneration for travel.  
Participants in the ancillary study may be provided with a small monthly remuneration (up to $10 
month for 7 months) to help offset costs of broadband and/or cellular services needed to 
participate. 
Measures and Data Collection 
Outcomes data will be collected at 0 (baseline, just prior to randomization), 3 (mid-intervention), 
6 (post-intervention), and 12 months (6 mos. after completion of the intervention (follow-up)). 
Written surveys are completed on a computer at the testing facility at baseline and online for 
follow-up visits. All measures are completed by both members of the couple at each wave. 
 
Primary Outcome Measure: 
1.  Dyadic coping 
Measured by the Relationship Focused Coping Scale to assess the degree with which 
couples practice active engagement and protective buffering using questions on a 
scale from 1 (never) to 5 (very often). 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
2.  Emotional intimacy 
Measured by the Dyadic Adjustment Scale (DAS) to assess each partner’s satisfaction 
with their relationship by answering questions on a 6-point scale ranging from 1(always 
agree) to 6 (always disagree). 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
3.  Physical intimacy 

 
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Measured by the Physical Intimacy Behavior scale which asks participants the 
frequency that they engage in, initiate, and avoid intimate behaviors using questions on 
scale from 1 (none of the time) to 4 (most or all of the time). 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
4.  Concealment of symptoms 
Measured by the Emotional-Intimacy Disruptive Behavior Scale. Patients report the 
extent to which they engage in 8 behaviors using a scale from 1 (rarely or none of the 
time) to 4 (most or all of the time). 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
5.  Symptom incongruence 
Measured by the degree of agreement between the survivor and spouse/partner 
ratings of the survivor’s pain, fatigue and physical function in the past week using the 
following instruments: the Brief Pain Inventory (BPI) to measure pain intensity and pain 
interference, Functional Assessment in Chronic Illness Therapy (FACIT) fatigue survey 
to measure fatigue, and perceived physical function using a subscale of the SF-36 
medical outcomes survey (all described below). 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
Secondary Outcome Measure: 
6.  Body composition 
Measured by bone-free lean and fat mass (kg) for the whole body determined from a 
whole body dual energy x-ray absorptiometry (DXA) (Hologic-QDR Discovery Wi; 
APEX software, v.4.02) scan and used to calculate the % body fat. 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
7.  Cardiovascular health: serum fasting lipids 
Measured by serum fasting lipids (total, high-density and low-density lipoprotein 
cholesterol and triglycerides) 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
8.  Cardiovascular health: insulin resistance 
Measured by Homeostasis Model Assessment – Insulin Resistance - HOMA-IR: as the 
product of glucose and insulin, obtained from a fasting blood sample, divided by a 
constant. 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
9.  Cardiovascular health: resting blood pressure 
Measured by the average of three consecutive resting blood pressure measurements 
(systolic and diastolic pressures). 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
10.  Inflammation 
Measured by serum levels of high sensitivity C-reactive protein (hsCRP) and tumor 
necrosis factor alpha (TNF alpha) obtained from a fasting blood sample. 

 
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[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
11.  Objective physical function 
Measured by the Physical Performance Battery (PPB) to determine a person’s ability to 
perform daily tasks independently. The PPB consists of 3 timed tests: 5 repeated chair 
stands, standing balance, and gait speed over 4 meters. Each test is scored 0 (unable) 
to 4 (completes without difficulty), based on quartiles of performance, then scores are 
summed. The possible range of scores is 0-12. 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
12.  Quality of life (QOL): QLQ-C30 and SF36 
Measures QOL in cancer patients including subscales of physical and mental 
functioning. The SF-36 Health Survey assesses QOL in the general population. 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
13.  Depressive symptoms 
Measured by the Center for Epidemiological Studies-Depression (CES-D) scale to 
determine the degree of depressive symptoms. 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
14.  Anxiety 
Measured by the PROMIS anxiety short form using questions on a scale ranging from 
1 (never) to 5 (always). 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
15.  Fear of recurrence 
Measured by the Fear of Recurrence scale to assess the amount of concern survivors 
have about their cancer returning in the future. Participants respond to questions 
ranging from 1 (strongly agree) to 5 (strongly disagree). 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
Other Pre-specified Outcome Measures: 
16.  Sexual function 
Measured by the NIH PROMIS® Sexual Function and Satisfaction survey 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
 
17.  Caregiver strain 
Measured by the 18-item Multidimensional Caregiver Strain Index and the 6-item Role 
Overload scale. 
[Time Frame: 0 baseline (just prior to randomization), 3, 6, and 12 months] 
Descriptive Measures 
Demographic variables, including age, education, income, insurance status, length of 
relationship, cancer type and treatments (survivor), medications and health habits will be 
measured at baseline by an in-house questionnaire and updated at subsequent visits. Clinical 
measures of weight and height will be made.  
 

 
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Presence of chronic medical conditions, used to characterize the health of the sample, will be 
measured by the Charlson Comorbidity Index,[85] a weighted index originally developed to predict 
mortality.  
 
Shared activities at each time point will be measured using 2 items developed and used by this 
team. Survivors and spouses/partners are asked to rate engagement in a) leisure activities 
together and b) exercise activities together on a 0-4 scale, with a follow-up open-ended question 
about types of activities engaged in.  
Process Measures 
Adherence. Adherence (% of prescribed sessions completed) will be tracked from attendance 
logs recorded by the exercise instructor to describe dose of exercise so that we can interpret and 
generalize our findings. Additionally, a single-item likert question will be asked of survivors and 
spouses/partners regarding how supportive they felt their partner was to them during the program 
and how supportive they felt they were to their partner. 
 
Establishing the training effect and dose of exercise. Documenting the presence and degree of a 
training effect from experimental programs is an important element of any exercise training 
study[86]. In the absence of these measures it would be difficult to interpret unexpected, i.e., null, 
study findings. The improvements in fitness from exercise training are also an indicator of the 
dose of training, which can be used to interpret study outcomes. Evidence that the Exercising 
Together program effectively increased muscle strength will be evaluated by 1-repetition 
maximum testing for leg press and bench press. We have used the 1-RM technique in 6 studies 
of cancer survivors (age range: 35-89 y.o.) with no adverse events. The 1-RM test will be 
conducted according to established protocols[87]. Our in-house CV for this measure is 0.05-
0.0688. During periods of hospital recommendations for decreased in-person contact, the 1-
repetition maximum testing for leg press and bench press will be substituted with a push-up test 
and plank test. These measures can be completed through video conferencing. To establish 
testing validity, these measures may also be completed in the testing lab when in-person contact 
resumes. 
. 
Additional Outcomes  
Physical activity (PA): To determine whether or not participation in Exercising Together changes 
overall PA levels and to compare our data against other studies that measure PA by self-report 
we will administer the 41-item Community Healthy Activities Model Program for Seniors 
(CHAMPS) PA questionnaire[88]. CHAMPS is a widely used and reliable[89] measure of PA in 
older adults that we’ve used in cancer survivors[38, 90-92]. 
 
Postural and dynamic stability will also be tested using the Mobility Lab ISWAY test and 6-min 
walk (APDM, Inc., http://apdm.com). The instrumented versions of the 6 min walk test and the 
Static Balance Test incorporate the use of wearable sensors to electronically detect changes in 
mobility beyond simple time measures or subjective scales. For each test, participants will wear 
six watch-sized movement sensors strapped to the wrists, ankles, chest, and waist using Velcro 
bands. The ISWAY consists of a 30-second trial of standing quietly and captures the amplitude, 
frequency, velocity and jerkiness of postural sway in multiple directions. This test will be 
completed once with the eyes open, feet together and once with the eyes closed, feet together. 
Postural sway is associated with balance control, is a strong predictor of falls, and is worse in 
those with neurological impairment.Mancini & Horak, 2010  
 
Cancer-related loneliness: Participation in group-based exercise may facilitate development of 
friendships and comradery with others around a shared experience of cancer, which may result 

 
12 
Protocol Version 21.0 – 05/17/2024 
in reduced feelings of loneliness. To assess changes in cancer-related loneliness, we will 
administer a validated cancer-related loneliness questionnaire, the Cancer Loneliness Scale Adams, 
2017, to survivors. We will administer a modified version of the Cancer Loneliness Scale to 
spouses/partners in which language referring to the cancer survivor is revised to refer to the 
cancer survivor’s intimate partner. We will administer the CLS and the modified CLS to newly 
enrolled participants. 
 
Intervention Feedback: To better assess program feasibility and acceptability, as well as capture 
participant experiences not possible from our standardized surveys, we will be administering a 
survey (Post-Intervention Survey) at the end of the 6-month intervention that includes both 
qualitative and quantitative questions about the participant’s experience in their assigned exercise 
program. 
 
Study visits may be delivered in-person with additional precautions during periods of hospital 
recommendations for decreased in-person contact, and/or delivered remotely via video 
conferencing. In order to determine the validity of remote delivery, participants may be asked to 
complete both sets of testing at every time point (in-person plus remote). In such cases 
remuneration will be offered to offset the additional time asked of participants. If delivered 
remotely, select testing measures will be adapted to this type of delivery. These testing measures 
include: 
1. Height (self-report collected if in-person assessment not expected) 
2. Weight 
3. Physical Performance Battery (PPB) (see 11. Objective physical function above, under 
Secondary Outcome Measures) 
4. All surveys (see 1-5 above, under Primary Outcome Measures, and 12-17 under 
Secondary Outcome Measures and Other Pre-specified Outcome Measures) will continue 
to be sent out electronically as previously described. If a participant needs a paper survey 
to complete the survey, one will be provided or their data will be marked as “missed” if 
study staff are unable to mail a paper survey to the participant during their outlined testing 
window.  
 
To assess upper body strength remotely, novel assessments to this trial will include: 
5. Push-up test 
Measured by the number of push-ups completed in one continuous bout until fatigue 
6. Plank test 
Measured by the amount of time in seconds that the participant is able to hold a plank 
position 
 
The following measures will not be collected remotely: 
1. DXA scan (see 6. Body composition above, under Secondary Outcome Measures) 
2. Resting blood pressure and blood draw (see 7-10. Cardiovascular health/Inflammation 
above, under Secondary Outcome Measures) 
3. Postural and dynamic stability (see Additional Outcomes above) 
4. 1-repetition maximum testing for leg press and bench press (see process outcomes 
above) 
 

 
13 
Protocol Version 21.0 – 05/17/2024 
Ancillary study: All study visits will be conducted remotely via videoconferencing. Measures will 
be collected in accordance with remote testing procedures described above.  
 
 
4.0 STUDY POPULATION  
For this study, we will recruit prostate, breast and colorectal cancer survivors and their co-residing 
spouse/partner, including both heterosexual intimate partners and same-sex couples. 
We aim to recruit 294 couples (588 participants). 
Ancillary study: We will recruit an additional 30 couples (60 participants) from five geographically 
underserved counties in Oregon (Wheeler, Malheur, Jefferson, Lake, and Benton counties). 
5.0 INCLUSION/EXCLUSION CRITERIA  
 
Inclusion Criteria: Survivors Only:  
• 
 Histologically confirmed PC, BC or CRC without evidence of metastatic disease 
(confirmed by self-report on Health History Questionnaire.  In the case a participant isn’t 
able to confirm this criterion, a letter will be sent to his or her physician) 
• 
Three years or less from diagnosis date, by month and year, at time of enrollment 
(confirmed by self-report on Health History Questionnaire.  In the case a participant isn’t 
able to confirm this criterion, a letter will be sent to his or her physician)  
• 
Completed treatment (e.g., surgery, radiation and/or chemotherapy) ≥6 weeks prior to 
enrollment. Concurrent adjuvant hormone therapy is permitted and must have been 
initiated ≥ 6 weeks prior to enrollment. For prostate cancer, Androgen Deprivation 
Therapy (ADT) may constitute primary treatment and must have been initiated ≥ 6 
weeks prior to enrollment. For breast cancer, hormone therapy may constitute primary 
treatment and must have been initiated ≥ 6 weeks prior to enrollment. (confirmed by self-
report on Health History Questionnaire.  In the case a participant isn’t able to confirm this 
criterion, a letter will be sent to his or her physician) 
• 
Co-residing with an intimate partner or spouse who is willing to participate (confirmed by 
self-report on Health History Questionnaire) 
Inclusion Criteria: Survivors and Spouses/Partners:   
• 
Age 35-80 years (confirmed by self-report on Health History Questionnaire) 
• 
Underactive (< 2 strength training sessions per week, lasting 30 minutes or more per 
session, at a moderate intensity in the last month) (confirmed by self-report on Health 
History Questionnaire or by discretion of the Principal Investigator) 
Exclusion Criteria: Survivors and Spouses/Partners:   
• 
Cognitive difficulties that preclude answering the survey questions, participating in the 
exercise classes or performance tests, or providing informed consent as determined by 
the professional opinion of the Principal Investigator, Dr. Kerri Winters-Stone.  
•    A medical condition, movement or neurological disorder, or medication use that 
contraindicates participation in moderate intensity exercise. Specific contraindications 
include the following: declared pregnancy, poorly controlled diabetes, recent cardiac 
event, neuromuscular disease, untreated orthostatic hypertension, recent surgery, acute 
hernia, acute rheumatoid arthritis, severe memory disorders, severe balance disorder, 
inability to ambulate (use of an assistive device permitted), inability to stand for 3 minutes, 

 
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Protocol Version 21.0 – 05/17/2024 
severe hearing or vision problem. (For Survivor: Confirmed by physician clearance; For 
Spouse/Partner: must answer ‘No’ to American College of Sports Medicine pre-
participation screening questions [103]. If spouse/partner answers ‘Yes’ to either question 
they will be considered eligible upon physician clearance. Physician clearance may also 
be requested at the discretion of the Principal Investigator. For either: absence of 
pregnancy in persons who could possibly be pregnant but have not declared a pregnancy 
at screening, will be further screened with a pregnancy test administered at each testing 
visit, unless only participating remotely.) 
 
• 
Knowingly unable to attend >75% of the intervention classes due to conflict with the 
designated time of day, days of the week, and/or location for the exercise class which 
they initially enrolled. (Confirmed by documentation in the Case Report Form titled “CRF 
- Participant Contact Info_Exercising Together”) 
 
• 
Not fluent in English and therefore incapable of answering survey questions, 
participating in class, following directions during performance testing, and providing 
informed consent when English is the language used. (Confirmed by documentation in 
the Case Report Form titled “CRF - Participant Contact Info_Exercising Together” or the 
professional opinion of the Principal Investigator, Dr. Kerri Winters-Stone.) 
Ancillary study: Participants recruited for the ancillary study will not be screened with a 
pregnancy test due to remote participation. 
Ancillary study: To expand the pool of eligible participants, we will including survivors with a 
longer interval since diagnosis, as below. 
Survivor only inclusion criterion: 
• 
Ten years or less from diagnosis date, by month and year, at time of enrollment 
(confirmed by self-report on Health History Questionnaire.  In the case a participant isn’t 
able to confirm this criterion, a letter will be sent to his or her physician)  
 
Ancillary study: Additional exclusion criteria: 
• 
Insufficient internet connectivity to support videoconferencing (Confirmed by 
documentation in the Case Report Form titled “CRF - Participant Contact 
Info_Exercising Together”) 
6.0 VULNERABLE POPULATIONS  
This study will not include any vulnerable populations.  We will not collect any information 
about subjects’ status as prisoners or pregnant women. Children will not be included 
because they do not get prostate, breast or colorectal cancer. 
 
 
7.0 SETTING (REQUIRED) 
The primary study site will be Oregon Health & Science University (OHSU). Testing will be 
conducted at the OHSU Knight Cancer Research Building and the Oregon Clinical Translational 
Research Institute (OCTRI). Exercise training will be offered at OHSU and several community 
sites serving different geographic regions of the Williamette Valley, including an exercise site in 
Salem, OR, 60 miles south of Portland so that we can develop and test features of delivering the 
program outside of a large urban area. Study visits and exercise training may be delivered 
remotely via video conferencing. Conferences are set up by a private link sent to participants by 

 
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Protocol Version 21.0 – 05/17/2024 
email. Any data recorded during training or study visits will be entered directly into databases on 
staff computers. 
 
Ancillary study: For participants enrolled in the ancillary study, study visits and exercise training 
will be delivered remotely via video conferencing. 
 
8.0 STUDY PROCEDURES AND SCHEDULE OF EVENTS  
Screening tests and procedures:  
Some potential participants will be sent a MyChart recruitment invitation via an email notification, 
as below, with the Subject “New Research Study” instructing them to log into MyChart to learn 
more and respond.  The text of this invitation and a description of the MyChart recruitment process 
is contained in Recruitment - EPIC MyChart procedures_20191210. The link in the MyChart 
invitation will take the potential participant to their MyChart homepage with a link to a description 
of the study.  The text for the study summary is contained in Recruitment - EPIC MyChart patient 
facing text_20191210.  Potential participants will express interest or decline by pressing the 
associated buttons in MyChart, or they will not respond.  If the potential participant indicates 
interest, they are automatically associated to the study in Epic with a status of “interested;” the 
study remains listed on the patient’s Research Studies page in MyChart, and the study team 
immediately receives an in basket notification in Epic so that they can follow up with the patient.  
If the patient clicks “No, Thank You” this study will no longer appear on their Research Studies 
page in MyChart, and the patient is automatically associated to the study in Epic with a status of 
“declined.”  The recruitment script for contacting potential participants that express interest in the 
study is contained in the document Screening - Phone Screen_Survivor_revised 20190212. 
 
Interested participants will be screened either by phone or in person using an IRB approved 
screening script.  After initial screening, interested and eligible couples will come to the OHSU 
Knight Cancer Research Building and will be presented with an online IRB-approved Consent 
Form prior to any study-related procedure. The Consent Form will describe the goals of the study, 
study procedures, confidentiality, risks, benefits, and voluntary nature of the research. After 
participants view the consent online, and click the box that they have read and agree to participate 
(indicating that they have signed the consent), they will be sent links and requested to complete 
REDCap surveys. For the baseline testing session, couples will be asked to provide a fasting 
blood draw (which may be completed at an appointment separate of the baseline consenting visit 
but prior to initiation of the intervention), blood pressure, DXA scan, physical tests (PPB, 1RM leg 
and bench press, standing balance, and 6 minute walk test), and questionnaires. The testing 
session will take ~2-3 hours per couple, initially, and will be repeated at 3, 6, & 12 months and 
only take 1-2 hours.  Following baseline testing, the Project Director will provide each couple with 
an envelope that contains their random assignment to a study group in order to retain blinding of 
the research assistants who conduct testing. Couples will be randomly assigned to 1 of 3 groups: 
1) Exercising Together, 2) Separate survivor / spouse/partner group exercise 3) Separate survivor 
/ spouse/partner home exercise. Enrollment will be stratified by cancer type and average couple 
age (<60 vs. 60-80). Assignment will be in random blocks of 6-9 couples for even enrollment. 
During periods of hospital recommendations for decreased in-person contact, re-consent for the 
modified procedures will be done over the phone or via teleconference. Study team members will 
inform the participants of the modified procedures and note their verbal agreement to continue on 
the study.  
Individuals who have not previously consented will be screened by phone or teleconference using 
an IRB approved screening script. After initial screening, interested and eligible couples will 

 
16 
Protocol Version 21.0 – 05/17/2024 
consent by an electronic consent process setup through OCTRI’s REDCap system (See 17.0 for 
a description of REDCap’s Privacy, Confidentiality, and Data Security). A waiver of documentation 
of consent will be used to waive the need for a legally valid signature, however, an electronic 
signature and affirmation of consent will be collected in REDCap. Study staff will sign an 
attestation form in REDCap after the participant consents. Study staff will proceed with following 
the outline for remote testing procedures, as previously described in section 3.0 Study 
Design/Methodology.  
Ancillary study: Individuals being recruited for the ancillary study will be screened by phone or 
videoconference using an IRB approved screening script, including screening questions about 
their internet connectivity and computer hardware for remote study participation. In order to 
assess participants’ ability to participate in videoconferencing, they may be asked to facilitate 
gathering information about their internet speed from their internet service provider. After initial 
screening, interested and eligible couples will consent by an electronic consent process setup 
through OCTRI’s REDCap system (See 17.0 for a description of REDCap’s Privacy, 
Confidentiality, and Data Security). A waiver of documentation of consent will be used to waive 
the need for a legally valid signature, however, an electronic signature and affirmation of consent 
will be collected in REDCap. Study staff will sign an attestation form in REDCap after the 
participant consents. Study staff will proceed with following the outline for remote testing 
procedures, as previously described in section 3.0 Study Design/Methodology. If a participating 
couple is provided with an internet-capable device (i.e. Chromebook or tablet), they will sign a 
Device Agreement prior to receiving the device. 
 
Intervention, tests or procedures:  
Regardless of group assignment, all participants will be expected to engage in 1-hr exercise 
sessions, 2 d/wk for 6 months.  The basic training program for all three study arms is a functional 
strength training program based on recommendations for improving muscle strength in adults[41] 
and our prior studies in cancer survivors. For safety reporting purposes, a monthly Adverse Event 
Survey will be sent electronically or completed over the phone. More details about this survey can 
be found under section 19.1 Monitoring Plan. 
Follow up tests and procedures:  
After the completion of the 6 month exercise intervention, all couples will be followed for an 
additional 6 months after formal training stops. Couples may wish to maintain their exercise habits 
or participate in shared activities other than exercise after formal training stops and we will not 
discourage them from doing so. To provide couples in supervised programs a resource to 
continue to engage in exercise after supervised training stops we will provide them with a DVD of 
their programs to use at home. 
All biomarkers of inflammation and cardiovascular health will be measured from blood obtained 
from participants by the Oregon Clinical Translational Research Institute (OCTRI), following 
established protocols.  Participants will be asked to fast and abstain from smoking cigarettes, 
drinking alcohol or drinking caffeinated beverages for 12 hours before the blood is drawn. 
The total duration of an individual subject’s participation in the study is 12 months. Certain data 
(questionnaires and adverse events follow-up) may be collected after this 12-month period, when 
a participant is off study, using IRB-approved language. With participant approval, we may contact 
a patient’s provider to confirm cancer history. 
When participants drop out of the research their data will be retained for analysis. If a participant 
becomes ineligible during the study s/he will be withdrawn by the investigator and data will no 

 
17 
Protocol Version 21.0 – 05/17/2024 
longer be collected; however, in these cases the participant would be allowed to continue in the 
study exercise program as long as the reason for ineligibility does not contraindicate exercise 
participation.  
Drop out of one exercise partner in Exercising Together arm: If one partner of a couple is unable 
or unwilling to continue exercise training, any data collected on them prior to their withdrawal will 
be used for purposes of this research.  Data will be continued to be collected on the other partner 
and they will be allowed to continue in the exercise program. If needed their program will be 
adapted so that it can be performed independently.  
The investigator may choose to withdraw a participant without their consent if his/her health 
changes and the study is no longer in their best interest, if new information becomes available, if 
he/she does not follow the study rules, and/or if the study is stopped by the IRB.  
 
SCHEDULE OF EVENTS 
Procedures 
Eligibility 
Screening 
Baseline 
Testing 
Intervention 
3-Month 
Testing 
6-Month 
Testing 
9-
Month 
check-
in 
12-
Month 
Testing 
Monthly  
- 
Month 
1 – 12 
Pre-screening eligibility 
x 
 
 
 
 
 
 
 
Consent form 
x 
 
 
 
 
 
 
 
Exercise (intervention) 
 
 
x 
 
 
 
 
 
Dyadic Coping 
 
x 
 
x 
x 
 
x 
 
Emotional intimacy - DAS 
 
x 
 
 
 
 
 
 
Concealment of symptoms – 
EIDB Scale 
 
x 
 
x 
x 
 
x 
 
Physical intimacy – The 
Physical Intimacy Behavior 
Scale 
 
x 
 
x 
x 
 
x 
 
Pain - BPI 
 
x 
 
x 
x 
 
x 
 
Fatigue - FACIT 
 
x 
 
x 
x 
 
x 
 
Depressive symptoms – CES-
D 
 
x 
 
x 
x 
 
x 
 
PROMIS Anxiety 
 
x 
 
x 
x 
 
x 
 
Fear of recurrence – F.O.R. 
scale 
 
x 
 
x 
x 
 
x 
 
Demographics – demographic 
questionnaire 
 
x 
 
 
 
 
 
 
Comorbidities – Charlson 
Comorbidity Index 
 
x 
 
x 
x 
 
x 
 
Shared activities 
 
x 
 
x 
x 
 
x 
 
Physical activity - CHAMPS 
 
x 
 
x 
x 
 
x 
 
Quality of Life – QLQ-C30 & 
SF-36 
 
x 
 
x 
x 
 
x 
 
Sexual Satisfaction – PROMIS 
Sexual  Satisfaction Survey 
 
x 
 
x 
x 
 
x 
 
Care strain – Role Overload; 
Multidimensional caregiver 
strain index (MCSI) 
 
x 
 
x 
x 
 
x 
 
Cancer-related Loneliness – 
Cancer Loneliness Scale 
 
x 
 
x 
x 
 
x 
 
Post-Intervention Survey 
 
 
 
 
x 
 
 
 
Inflammation & cardiovascular 
health--blood draw 
 
x 
 
x 
x 
 
x 
 
Exercise Follow-up Survey 
 
 
 
 
 
x 
x 
 
Adverse Event Survey 
 
 
 
 
 
 
 
x 
Body composition-DXA 
 
x 
 
x 
x 
 
x 
 
Resting Blood Pressure 
 
x 
 
x 
x 
 
x 
 

 
18 
Protocol Version 21.0 – 05/17/2024 
Procedures 
Eligibility 
Screening 
Baseline 
Testing 
Intervention 
3-Month 
Testing 
6-Month 
Testing 
9-
Month 
check-
in 
12-
Month 
Testing 
Monthly  
- 
Month 
1 – 12 
Physical functioning-PPB, 
iSWAY, 6-minute walk 
 
x 
 
x 
x 
 
x 
 
Muscle strength-1RM leg & 
bench press 
 
x 
 
x 
x 
 
x 
 
Push-up test* 
 
x 
 
x 
x 
 
x 
 
Plank test* 
 
x 
 
x 
x 
 
x 
 
*Conducted during remote testing visits. For validity purposes, these measures may also be completed in the testing lab when in-
person contact resumes. 
 
Ancillary study: SCHEDULE OF EVENTS 
 
Procedures 
Eligibility 
Screening 
Baseline 
Testing 
Intervention 
3-Month 
Testing 
6-Month 
Testing 
9-
Month 
check-
in 
12-
Month 
Testing 
Monthly  
- 
Month 
1 – 12 
Pre-screening eligibility 
x 
 
 
 
 
 
 
 
Consent form 
x 
 
 
 
 
 
 
 
Exercise (intervention) 
 
 
x 
 
 
 
 
 
Dyadic Coping 
 
x 
 
x 
x 
 
x 
 
Emotional intimacy - DAS 
 
x 
 
 
 
 
 
 
Concealment of symptoms – 
EIDB Scale 
 
x 
 
x 
x 
 
x 
 
Physical intimacy – The 
Physical Intimacy Behavior 
Scale 
 
x 
 
x 
x 
 
x 
 
Pain - BPI 
 
x 
 
x 
x 
 
x 
 
Fatigue - FACIT 
 
x 
 
x 
x 
 
x 
 
Depressive symptoms – CES-
D 
 
x 
 
x 
x 
 
x 
 
PROMIS Anxiety 
 
x 
 
x 
x 
 
x 
 
Fear of recurrence – F.O.R. 
scale 
 
x 
 
x 
x 
 
x 
 
Demographics – demographic 
questionnaire 
 
x 
 
 
 
 
 
 
Comorbidities – Charlson 
Comorbidity Index 
 
x 
 
x 
x 
 
x 
 
Shared activities 
 
x 
 
x 
x 
 
x 
 
Physical activity - CHAMPS 
 
x 
 
x 
x 
 
x 
 
Quality of Life – QLQ-C30 & 
SF-36 
 
x 
 
x 
x 
 
x 
 
Sexual Satisfaction – PROMIS 
Sexual  Satisfaction Survey 
 
x 
 
x 
x 
 
x 
 
Care strain – Role Overload; 
Multidimensional caregiver 
strain index (MCSI) 
 
x 
 
x 
x 
 
x 
 
Cancer-related Loneliness – 
Cancer Loneliness Scale 
 
x 
 
x 
x 
 
x 
 
Post-Intervention Survey 
 
 
 
 
x 
 
 
 
Exercise Follow-up Survey 
 
 
 
 
 
x 
x 
 
Adverse Event Survey 
 
 
 
 
 
 
 
x 
Physical functioning-PPB 
 
x 
 
x 
x 
 
x 
 
Push-up test 
 
x 
 
x 
x 
 
x 
 
Plank test 
 
x 
 
x 
x 
 
x 
 
 

 
19 
Protocol Version 21.0 – 05/17/2024 
9.0 DATA AND SPECIMENS (REQUIRED) 
a) Handling of Data and Specimens 
 
All contact information collected from the study, including name, mailing address, phone number 
and email address, will be stored on an encrypted and password protected computer drive in 
the OHSU Knight Cancer Research Building that only IRB approved persons have access to.  
 
All other data collected for this study including answers from the health history form (e.g. DOB, 
education, income, demographics, as well as cancer specific information such as diagnosis, 
type & dates of cancer treatments), answers to the study surveys, and results from the physical 
tests will be stored in OCTRI's installation of REDCap, a highly secure and robust web-based 
research data collection and management system. 
 
Data that may be collected from a patient’s electronic medical record would include contact 
information including phone number, mailing address and email address, as well as cancer 
specific information such as diagnosis, type & dates of cancer treatments.  Any data collected 
will be stored on an encrypted and password protected computer drive in the OHSU Knight 
Cancer Research Building that only IRB approved persons have access to.  
 
Consent forms and any surveys that were filled out on paper will be stored in a locked cabinet in 
a locked, secure room in the Knight Cancer Research Building. Documentation of the consent 
process and a copy of the signed consent will be maintained in the patient’s medical record. 
 
Data from the HHQ, surveys and physical tests will be transported by secure electronic 
transmission (i.e. secure, encrypted email or stored on a secure shared drive such as Box). 
 
The PI will be responsible for the receipt or transmission of the data. 
 
Data used and collected for purposes of this study will be stored until data analysis is complete 
and then the data will be transferred to a repository. All data received from OSCaR for purposes 
of eligibility/recruitment purposes will be destroyed after the purposes of the research have been 
fulfilled.  Electronic files will be deleted from the secured drive used by the study team. 
 
 
b) Sharing of Results with Subjects 
Results of the physical tests will be shared with the subjects 
 
c) Data and Specimen Banking 
Specimens and data from this study will be banked in a repository for future use as part of 
this protocol. Data may be stored indefinitely while blood samples will be stored for no 
more than 20 years. Access to data/specimens is restricted to study personnel. 
Data/specimens released to other investigators will be labeled with only the code assigned 
to each participant at enrollment. This same unique identifier, along with the date of 
specimen collection, will be used to label blood samples taken and for storage. 
 
After the study is complete, all contact information (e.g., name, mailing address, phone 
number) and data from the HHQ, study surveys and physical tests will be stored in a private 
locked-repository (IRB# 7553) at OHSU Knight Cancer Research Building.  The contact 
information will be stored separately from the other data. The repository will be managed by 
Dr. Kerri Winters-Stone, the Principal Investigator of the study.  All of the data from the 
surveys and physical tests will be coded with a unique ID number that doesn’t contain any 

 
20 
Protocol Version 21.0 – 05/17/2024 
PHI.  The list matching the PHI and the ID number is stored in a password protected 
document on a password protected computer drive in the OHSU Knight Cancer Research 
Building that only IRB approved persons have access to.  Only IRB approved research staff 
will have access to the password and computer drive where this record is stored. Any 
requests made for the use of the data will be evaluated by the repository guardian, Kerri 
Winters-Stone, who will create a subset of eligible data using OHSU IRB confidentiality 
procedures.  The repository guardian will apply an algorithm to the ID numbers on the data 
subset, therefore, creating a new unique identifier for each data that will be used.  This will 
ensure that only the guardian can link the data back to original study ID numbers and 
corresponding PHI. Only the guardian will have access to this algorithm.  Any future human 
subject research study that wants to use the data or contact information from the repository 
will require separate IRB approval.  The usage requirements will be limited to the principal 
investigator, co-investigators and associates from the original research studies.  Any future 
study requesting use of the data must either be related to the original research study or 
explore new and innovative research questions approved by the guardian.   
 
10.0 
RISKS TO SUBJECTS  
The risks to human subjects include potential adverse effects of exercise. Risks of participation 
include tiredness from answering research questions or participating in exercise, anxiety about 
ability to read surveys or reach exercise goals, discouragement about ability to exercise, worry 
about loss of confidentiality/privacy, and perception of coercion to participate. Additional risks to 
participation include phlebotomy and radiation exposure. With respect to venipuncture 
procedures in general, some participants may experience temporary discomfort. Extremely rare 
risks associated with venipuncture are bleeding, fainting or feeling lightheaded, hematoma, or 
infection. With respect to radiation exposure, there is minimal radiation exposure associated with 
a whole body DXA scan (<1 μSv), which is less than half of radiation received on a one-way trip 
from California to New York and has negligible health risks.   
 
Ancillary study: Participants in the ancillary study will not incur risks from phlebotomy or radiation 
exposure. Participants in the ancillary study may be provided with an internet-capable device (i.e. 
Chromebook or tablet) to help them access the study, and use of the device may pose a risk of 
loss of confidentiality/privacy. 
 Adequacy of Protection Against Risks 
a. Recruitment and Informed Consent 
The Oregon State Cancer Registry (OSCaR) will be the primary means used to recruit 
participants. Established in 1996, the registry is nationally recognized for the accuracy and 
completeness of its data. All tumors, except common skin cancers, are required to be reported 
by hospital registries, clinics, cancer treatment centers, and physician offices in Oregon and 
neighboring states where Oregon residents are treated. Patient’s data is reported, checked for 
quality assurance, and entered into OSCaR within six months of diagnosis. OSCaR procedures 
are well established and designed to protect persons in the registry. When each person’s data is 
entered in the registry, the individual is sent a letter asking if he is willing to be contacted about 
opportunities to participate in research studies. Very few refuse to be contacted. 
 
Potential participants will be identified by OSCaR for their cancer type (prostate, breast, 
colorectal), cancer treatment (surgery, radiation and/or chemotherapy), age, and zip code. 
OSCaR will then send identified patient data including the patient's physician information to our 
team using secure electronic transmission (i.e. encrypted flashdrive, secure encrypted email or 
stored on a secure shared drive such as Box). Data from OSCaR is only being used for purposes 

 
21 
Protocol Version 21.0 – 05/17/2024 
of identifying eligible patients and from this point forward is no longer involved in the research.  
Our team will then send an information letter about the study to listed physicians for identified 
persons in the registry, notifying the physician that their patient will be sent information about the 
study. Physicians who determine that their patients should not receive study information are 
asked to return a form to the study investigator within a 3-week period. These persons will no 
longer be considered eligible to receive study information. All other potential participants will be 
sent an information letter briefly describing the study along with a response form and contact 
information of the research team. Persons who are interested in receiving more information about 
the study are asked to either contact our team directly (phone, email, text) or complete the 
response form and return it to our team. For all response forms returned to our team and in 
response to all other forms of inquiry, a member of the research staff will then contact interested 
persons to provide more study information to them and to screen for eligibility if they indicate a 
willingness to participate.  
  
Potential participants will also be recruited via a study information mailing through the OHSU 
Cancer Registry and interested participants will contact us if they would like to learn more about 
the study and to check for eligibility. In addition we will recruit at community events, such as 
patient conferences and fundraisers, through study advertisements placed through various media 
outlets (i.e., internet, newspaper, radio), and by referral from the OHSU Prostate Cancer Clinic.  
 
Ancillary study: Participants may also be recruited through the Oregon Office of Rural Health or 
the Oregon Rural Practice-based Research Network. 
 
 
Members of tthe research team, will consult on eligibility issues as needed during recruitment. 
Eligible persons will come to the OHSU Knight Cancer Research Building to be consented and 
undergo baseline measures. Participants will also visit the OHSU Oregon Clinical Translational 
Institute for a blood draw collection at each measurement point.  
 
Ancillary study: Participants in the ancillary study will participate remotely and will not visit OHSU. 
 
b. Protection Against Risk 
As with any form of exercise, there is a slight risk of injury. We have not had a single participant 
drop out of a study due to an injury related to the exercise program; however, as with any study 
in older adults, exercise adherence has been affected by minor musculoskeletal complaints and 
are typically exacerbations of pre-existing orthopedic conditions. We will take the following steps 
to reduce the risk of injury and symptoms/side from exercise training: 1) Physician clearance: We 
will send a notice to each participant’s oncologist (or primary care provider) asking him or her to 
clear the participant for participation in any of the study exercise programs prior to beginning 
exercise training. If a wo/man’s physician does not clear him for participation we will inform the 
participant and refer him/her to her physician for clarification of the decision, 2) Monitor for and 
treat early musculoskeletal symptoms: From experience in our prior trials we have developed an 
injury prevention education and monitoring program. At the beginning of each participant’s start 
in the intervention he is provided general injury prevention information from the Project Director 
and exercise trainer. During the intervention the exercise trainer will consult with the Project 
Director on any reported exercise-related injuries and/or physical complaints from participants 
that affects their ability to do their exercise program. The Project Director will consult with 
participants on an individual basis, as needed, and will advise on treatment of their 
injury/complaint and when referral to a health practitioner is appropriate. The Project Director will 
work with the study team to document and track minor and major complaints and injuries in order 

 
22 
Protocol Version 21.0 – 05/17/2024 
to evaluate the overall safety and appropriateness of the study interventions for the study 
population. 
 
During testing visits, if a participant experiences tiredness, s/he will be told s/he can stop 
answering research questions, or participating in performance or clinical testing, and begin again 
at a later time. If tiredness occurs during exercise sessions, participants may rest as often as 
needed. If a participant is anxious about ability to read surveys, we will offer to ask the questions 
verbally and fill out the survey by telephone, if anxious about ability to reach exercise goals or 
discouraged about ability to exercise, Project Director, in consultation with the PI Winters-Stone, 
will problem-solve and support the participant in changing goals or developing alternative 
methods to meet goals. If a participant is worried about privacy and confidentiality of data, the 
Project Manager will discuss the methods for maintaining confidentiality: individual data will be 
identified only by a study ID number and only one computer file will link ID numbers with 
identifiable data; all computer records will be protected by a password known only to authorized 
study personnel; paper documents, such as surveys or computer disks, will be kept in locked files, 
and results will presented as group data only. To prevent the perception of coercion to participate, 
participants will be told they may decide to discontinue participation in the study at any time, that 
non-participation will not affect their usual care at their local clinic or at OHSU, and that data on 
non-participation will be kept confidential, using the methods described above. 
 
During remote exercise and testing sessions, additional safety precautions will include: 1) 
Providing safety recommendations specific to exercises and/or assessments (i.e., standing near 
a wall for balance activities) 2) Adapting the exercise protocol  as necessary (ie. limit weight.) 3) 
Verifying address of remote exercise location (i.e., home address), should the exercise instructor 
or Research Assistant need to call 911 in an emergency 4) Ensuring that emergency contact 
information is up-to-date and readily available. 
 
To minimize risks associated with phlebotomy, all venipuncture will be conducted by trained 
personnel from the Oregon Clinical Translational Research Institute (OCTRI) nursing services 
staff in adherence with OHSU Patient Care Services policy on venipuncture techniques for blood 
sampling. Serum samples will be labeled with participants unique study identifiers and will be 
subsequently stored in the OCTRI core laboratory. OCTRI is supported by the NIH specifically for 
the purposes of translational research, and the OCTRI core laboratory performs all procedures in 
accordance with guidelines issued by the Clinical and Laboratory Standards Institute, American 
Association for Clinical Chemistry, American Society for Clinical Pathology and other professional 
organizations appropriate to each specialty. To minimize risk against excess radiation exposure 
from DXA, whole body DXA scans will be conducted by the RA who will have been trained by the 
Principal Investigator and/or Project Director. Whole body DXA scans will be performed according 
to standard protocols which allows for early repositioning to minimize patient exposure.  
 
Ancillary study: Participants in the ancillary study will not incur risks from phlebotomy or radiation 
exposure. 
 
Participants in the ancillary study may be provided with an internet-capable device (i.e. 
Chromebook or tablet) to videoconference with the research team. To minimize risks to participant 
confidentiality/privacy, participants will be asked to only use the device for study-related activities, 
and we will recommend that participants lock the device with a password when not in use.  
 
 
11.0 
POTENTIAL BENEFITS TO SUBJECTS  
Participants may or may not personally benefit from being in this study. 

 
23 
Protocol Version 21.0 – 05/17/2024 
 
12.0 
TIMELINE & MILESTONES  
Participants are recruited in 10 waves (W1, W2, …); WG = geographically underserved wave (ancillary study); Quarters are 
approximate time points 
 
13.0 
BIO-STATISTICAL CONSIDERATIONS  
Power and Sample Size 
Required sample size was derived for the outcomes of Aim 1. Power analysis using traditional 
assumptions of the repeated measures ANOVA model suggest that as few as 174 couples would 
be necessary to detect a small effect (d=.20) between groups over time, an effect smaller than 
the observed effect on affectionate behavior in spouses/partners in our previous work[40]. 
However, these traditional power calculations are known to be optimistic. While there are good 
power formulae for MLM clustered designs and repeated measures designs, as yet there is no 
specific formula for calculating power for dyadic analyses. Using a formula provided by 
Raudenbush and Bryk[104, 105] for individual repeated measures and estimates from our 
previous dyadic models, we calculate a sample of 264 couples measured 4 times over a 12-month 
period has a power of 0.80 to detect a moderate effect (d=.40) on change over time. As dyad 
models using MLM control for interdependence between members of the couple, power is 
increased over an individual model. We, therefore, believe this to be a more conservative estimate 
of power. Further attempts to increase power and reduce Type I error will be to use the omnibus 
hypothesis-testing procedure in the HLM program. Another rule-of-thumb is to require a minimum 
number of subjects per parameter estimated. Even in the most complicated model, the proposed 
sample of 264 couples would exceed the minimum standard of 5-10 subjects per parameter 
estimated.[106] No universal approach has been adopted for sample size considerations in GMM 
and this will be used in an exploratory aim; however, our n-to-items ratio exceeds sample size 
recommendations for related approaches (10-20:1).[107] In sum, the proposed sample size of 264 
couples is on par with our previous trials and will allow us to detect clinically meaningful change 
and address study aims. To insulate the sample size against an estimated attrition of 10% across 
the study period, 294 couples will be randomized. The attrition estimate is more conservative than 
our prior trial of Exercising Together where no couples in the exercise program dropped out and 
the drop out in our current GET FIT trial that average 6% for a 6-month intervention. Couples will 
be enrolled into 10 waves (a new wave begins every 3-4 months) of 9-10 couples to maintain 
reasonable class sizes and make efficient use of testing resources. We will recruit approximately 
even numbers of couples coping with each type of cancer (N=98 per disease site) and stratify by 
cancer type at randomization. 
 
Analysis Plan 
Standard descriptive statistics/graphics will be used to check for any departures from statistical 
assumptions (e.g., normality, outliers, etc.).[108] We will examine dropout and patterns of missing 
data to determine mechanisms (MCAR, MAR, or not ignorable). In the case of data missing MCAR 
or MAR, model-based maximum likelihood estimation available in the MLM approach will allow 
unbiased parameter estimation using all available data (i.e., missing data is handled efficiently 
Project Timetable 
Y1  
Y2  
Y3 
Y4 
Y5 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Finalize protocols, databases 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hire/train research assistants 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hire/train exercise instructors 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
Recruit, enroll, baseline visit 
 
 
W1 
W2 
W3 
W4 
 
W5 
W6 
W7 
WG 
W8 
W9 
 
W10 
 
 
 
 
 
Start 6-month intervention 
 
 
W1 
W2 
W3 
W4 
 
W5 
W6 
W7 
WG 
W8 
W9 
 
W10 
 
 
 
 
 
Mid- & post-intervention visits 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
6-month follow up visit 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
x 
 
 
Data cleaning and analysis  
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Present and publish results 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 

 
24 
Protocol Version 21.0 – 05/17/2024 
with no loss of information).[109, 110]  If the rate of attrition is high and missing data is not ignorable, 
we will continue with the planned analyses but temper our conclusions. For each aim, we will 
conduct intention-to-treat (ITT) and completers only analyses. ITT analyses will include all 
participants regardless of adherence to exercise regimen. Based on median attendance data from 
our prior trials, completers will be defined as participating in 50% or more of the scheduled 
exercise sessions. We will track medical treatment changes, cancer recurrence, and adherence 
to exercise. Age, comorbidities and time since diagnosis will be considered as covariates in all 
analyses. All analyses will be conducted in R and HLM statistical software packages (Aim 4 will 
be conducted using MPlus v7.2). 
Aim 1: Determine the efficacy of partnered strength training on relationship quality (intimacy, 
communication and incongruence). A longitudinal multivariate-outcomes dyad model will be used 
to directly examine couple trajectories in intimacy (emotional & physical) and communication over 
time. This is a multi-level model where responses from the survivor and spouse/partner are 
modeled simultaneously to control for the interdependent nature of the data and autocorrelation 
among repeated assessments. These models have been described and used extensively by Co-
PI Lyons.[22, 111-113] The Level 1 model has four coefficients representing intercepts  (baseline 
assessments) and slopes (rates of change) for survivors and spouses/partners that become 
outcome variables in a Level 2 model. Models with linear and quadratic change across time will 
be compared to determine best fit to the data. Aim 1 will be addressed with Level-2 models that 
include dummy variables to directly examine the effects of the partnered intervention vs. 
supervised individual (dummy 1) and unsupervised individual (dummy 2) exercise groups on 
individual level changes (controlling for couple effects) in intimacy and communication across 
time. A significant group coefficient on the slopes at level 2 and significantly better fitting model 
(evidenced by deviance statistic) will indicate the rate of change across time is different depending 
on a treatment group (i.e., interaction effect). We will also explore the efficacy of Exercising 
Together on incongruence (regarding survivor pain & fatigue) in couples. Univariate-outcomes 
models will be used to generate Empirical Bayes estimates of the gap between survivor and 
spouse/partner over time for each symptom measure. This comprehensive approach to 
estimating incongruence has been described elsewhere[114-116] and successfully used by this 
team.[55, 63, 113, 117, 118] The effect of Exercising Together on incongruence will be directly 
tested (similar to above model) by a significant coefficient for one of the two GROUP variables on 
the slope parameter and significantly better fitting model.  
   
Aims 2: Determine the efficacy of partnered strength training on physical and mental health. 
Separate longitudinal multivariate-outcomes models will be used to directly examine the effect of 
partnered strength training in couples on each physical (body composition, lipids, insulin 
resistance, blood pressure, inflammation, and physical function)  and mental health outcome 
(anxiety, depressive symptoms, fear of recurrence) as described above under Aim 1.  
 
Aim 3: Determine the persistence of Exercising Together. Sustained effects will be tested by 
comparing linear and quadratic trajectories across time (as discussed above). We will also 
separately estimate and directly compare the intervention effects between the intervention 
(baseline to 6 months) and follow-up (6 months to 6 months after end of intervention) periods.  
 
Aim 4: Exploratory analyses: Patterns and predictors of types of couples who benefit the most. 
GMM identifies distinct patterns of change that vary around different means, have unique variance 
and homogenous within-trajectory growth. Based on conditional probabilities, cases are assigned 
to the “most likely class” or pattern of change over time (e.g., couples who benefit/improve most 
from the intervention). Couple-level estimates from Aims above will be integrated into progressive 
GMM to determine if there are distinct and naturally-occurring patterns of change in outcomes 
over time with the dyad as the unit of analysis. Survivor-, spouse/partner- and couple-level 

 
25 
Protocol Version 21.0 – 05/17/2024 
determinants of fitting one pattern of change over the other(s) will be modeled using logistic, 
multinomial or ordinal regression as appropriate. This integrated multilevel and mixture modeling 
approach has been used previously by this team,[118]  as it allows us to identify types of dyads 
and differentiate them based on individual and couple-level factors. Finally, based on our pilot, 
we expect the intervention to have a positive effect on relational outcomes although it is possible 
that in a larger trial a small subgroup of couples will experience poorer outcomes; identifying 
characteristics of each common type of couple will allow interpretation of the generalizability of 
our findings. 
 
Additional Analyses: Gender as a Moderating Variable: We will also explore the moderating 
effect of gender on the effectiveness of Exercising Together in couples coping with different 
cancers (e.g., do women benefit more than men) after controlling for role (i.e., survivor vs 
spouse/partner). Interaction terms will be added to models described above to test for moderating 
effects.     
 
Ancillary study: Feasibility and acceptability of the ancillary study will be determined by calculating 
accrual, retention, and adherence rates, number of adverse events, and the proportion of testing 
visits and surveys completed. Feasibility and acceptability metrics will be compared to those of 
the parent trial. 
 
14.0 
RECRUITMENT METHODS  
We have planned for a 36-month enrollment period (see Timeline) to recruit 294 couples into the 
proposed study (~8 couples/month). Our main recruitment strategy will be through the Oregon 
State Cancer Registry. We have used OSCaR in previous studies allowing us to target 
recruitments by cancer site and proximity to exercise locations. Between 50%-80% of potential 
participants in our prior trials are respondents from OSCaR recruiting efforts. Current records 
indicate that there are 2616 living persons who were diagnosed with PC, BC and CRC in Oregon, 
that are between the ages of 40-70 years old, within 2 years of diagnosis, and who live within a 
10-mile radius of the Portland metro area. Based on our prior recruitment for our pilot of Exercising 
Together and GET FIT using OSCaR, 28% respond to recruitment letters and of those 65% were 
eligible and then 55% enroll, for an overall enrollment rate from the registry of 10%. Using OSCaR 
for the current trial would be expected to yield 261 participants, close to our target sample size. 
Other strategies that we will employ are: 1) Clinician referral through OHSU Hospital and 
Community Oncology clinics that serve outer Portland area. Physicians referral accounted for 
~15% of past enrollees and, 2) Direct community recruitment using newspaper ads, radio, web 
and presentations at cancer organizations and conferences, which recruited 25% of participants 
in our previous cancer exercise trials. Patients may also be recruited through Tuality Healthcare, 
or Adventist Medical Center. Additional recruitment will occur by obtaining data (name, phone 
number, email, address, cancer diagnosis and treatment information) from OCTRI’s Cohort 
Discovery, OCTRI’s Research Data Warehouse, and OHSU’s Medical Records. After obtaining 
this demographic data, recruitment will occur via letters, e-mails, phone calls, or 
letters/announcements via MyChart. 
 
This study will use Epic MyChart® to recruit potential participants. Researchers will work with 
ITG and/or OCTRI to identify potential participants based upon the above eligibility criteria. 
Researchers will create a Reporting Workbench query in epic based on inclusion and exclusion 
criteria. Potential participants will be sent a MyChart® recruitment message asking them to 
participate. There is no risk of duplicate invitations as it is based on MyChart® accounts 
combined with Epic records and no duplication is possible.  
 

 
26 
Protocol Version 21.0 – 05/17/2024 
Clinical practice head at each site will be contacted about the study and their permission will be 
obtained before any message is sent. 
 
Ancillary study: Participants may also be recruited through the Oregon Office of Rural Health or 
the Oregon Rural Practice-based Research Network. 
 
 
15.0 
INFORMED CONSENT (REQUIRED, UNLESS A WAIVER OR ALTERATION IS 
APPROVED BY THE IRB) 
 
Written informed consent will be obtained from all participants. A copy of the consent form and 
documentation of consent will be maintained in the participant’s medical record as well as 
stored in a study file kept in a locked cabinet in the Knight Cancer Research Building (for paper 
documents only) or stored on an encrypted and password protected computer drive in the 
OHSU Knight Cancer Research Building (for electronic consents and scanned PDFs of paper 
consents). Electronic data, including the electronic consent, will also be stored in a web-
accessible REDCap database housed on an OHSU secure server. 
Interested and eligible participants will go to OHSU Knight Cancer Research Building to meet 
with the study coordinator to sign an online IRB-approved Consent Form prior to any study-
related procedure. The Consent Form will describe the goals of the study, study procedures, 
confidentiality, risks, benefits, and voluntary nature of the research. After they view the consent 
online, and click the box that they have read and agree to participate (indicating that they have 
signed the consent), they will be sent links and requested to complete REDCap surveys. The 
study coordinator and PI will make themselves available throughout the consent process to 
answer any questions regarding the study.  The study coordinator will ask the participant to 
reflect back the details of the study to ensure the participant’s understanding. The participant 
will also be given a copy of the consent form to take home and refer to whenever needed.  
Participants will be told that participation is voluntary and they may discontinue participation at 
any time and that participation will not affect their usual care at OHSU. 
 
During periods of hospital recommendations for decreased in-person contact, re-consent for the 
modified procedures will be done over the phone or via teleconference. Study team members 
will inform the participants of the modified procedures and note their verbal agreement to 
continue on the study.  
Individuals who have not previously consented will consent by an electronic consent process 
setup through OCTRI’s REDCap system (See 17.0 for a description of REDCap’s Privacy, 
Confidentiality, and Data Security). A waiver of documentation of consent will be used to waive 
the need for a legally valid signature, however, an electronic signature and affirmation of 
consent will be collected in REDCap. Study staff will sign an attestation form in REDCap after 
the participant consents.  Study staff will proceed with following the outline for remote testing 
procedures, as previously described in section 3.0 Study Design/Methodology. 
 
Ancillary study: Individuals being recruited for the ancillary study will consent by an electronic 
consent process setup through OCTRI’s REDCap system (See 17.0 for a description of 
REDCap’s Privacy, Confidentiality, and Data Security). A waiver of documentation of consent 
will be used to waive the need for a legally valid signature, however, an electronic signature and 
affirmation of consent will be collected in REDCap. Study staff will sign an attestation form in 
REDCap after the participant consents. Study staff will proceed with following the outline for 
remote testing procedures, as previously described in section 3.0 Study Design/Methodology.  

 
27 
Protocol Version 21.0 – 05/17/2024 
 
 
16.0 
CHANGES TO PROTOCOL  
Any modification of this protocol must be documented in the form of a protocol revision or 
amendment signed by the principal investigator and approved by the Knight Cancer Institute 
and the IRB before the revision or amendment may be implemented. The only circumstance in 
which the amendment may be initiated without regulatory approval is for a change necessary to 
eliminate an apparent and immediate hazard to the patient. In that event, the investigator must 
notify the IRB in writing within 5 working days after the implementation.  
 
17.0 
PRIVACY, CONFIDENTIALITY, AND DATA SECURITY  
 
Standard institutional practices will be followed as described in the OHSU Information Security 
and Research Data Resource Guide (http://ozone.ohsu.edu/cc/sec/isg/res_sec.pdf) to maintain 
the confidentiality and security of data collected in this study. Study staff will be trained with 
regard to these procedures. 
 
Paper files will be stored in locked filing cabinets in restricted access offices at OHSU Knight 
Cancer Research Building.  
 
Electronic data will be stored on an encrypted and password protected computer drive in the 
OHSU Knight Cancer Research Building. 
 
  
Electronic data will also be stored in a web-accessible REDCap database housed on an OHSU 
secure server. Features of REDCap that protect participants' privacy and data security include: 
 
·   Physical Security: OCTRI's REDCap software is housed on servers located in 
ITG's Advanced Computing Center providing locked physical security 
·        Electronic Security: The REDCap servers are housed behind both the OHSU 
firewall and a second ACC firewall.  All web-based data transmissions are encrypted 
with industry-standard SSL methods.   
·        Controlled User Access: REDCap is employs a robust multi-level security 
system that enables researchers to easily implement "minimum necessary" data access 
for their research staff, including specification of data fields that are identifiers. This 
feature includes “single click” ability to provide completely deidentified (removing all 
identified data fields and shifting dates) for analysis or other purposes.  User activities 
are logged to enable auditing of all data access.   Access is integrated with OHSU's 
network such that users who are also OHSU employees are authenticated against their 
OHSU network credentials.   
·        Data Integrity: REDCap is jointly managed in accordance with OHSU 
Information Security Directives by ACC staff and members of OCTRI's Biomedical 
Informatics Program, ensuring fidelity of database configuration and back-ups.  User 
activities are logged to enable auditing of all data changes. 
 
 
Access to data/specimens is restricted to study personnel and requires OHSU ID/password 
authentication. 
 
 

 
28 
Protocol Version 21.0 – 05/17/2024 
Upon enrollment, subjects will be assigned a code that will be used instead of their name, 
medical record number or other personally identifying information. Electronic files for data 
analysis will contain only the subject code.  
 
Codes will not contain any part of the 18 HIPAA identifiers (initials, DOB, MRN)  
 
The key associating the codes and the subjects personally identifying information will be 
restricted to the PI and study staff. The key will be kept secure on a restricted OHSU network 
drive in a limited access folder. 
 
Data will be transferred in files using encryption.  
 
Data/specimens released to other investigators will be labeled with only the code. 
 
Data/specimens from this study will be banked in a repository for future use as part of this 
protocol. Access to data/specimens is restricted to study personnel.  
 
18.0 
OHSU IRB REPORTING OF UNANTICIPATED PROBLEMS AND ADVERSE EVENTS  
Reportable New Information (RNI) will be reported to IRB according to the policies, procedures 
and guidelines posted on the OHSU IRB web site:  
• 
Fatal and life-threatening events will be reported to OHSU IRB within 5 days of 
notification of the event.  All other reportable events will be submitted to OHSU IRB no 
later than 5 working days of occurrence or notification of the event. Copies of the report 
documents will be kept in the study regulatory binder.  
• 
Reportable events are submitted through OHSU eIRB and will be reviewed by OHSU 
Knight Cancer Institute DSMC and IRB.   
19.0 
OHSU KNIGHT CANCER INSTITUTE DATA AND SAFETY MONITORING PLAN 
In addition to complete study and pharmacy files, complete records must be maintained on each 
patient enrolled on this protocol. OHSU Knight Clinical Research Quality and Administration 
(CRQA) shared resource is responsible for ensuring that all member investigators and affiliate 
investigators conduct clinical research studies in compliance with local IRB standards, state 
laws, FDA regulations (where applicable), Department of Health & Human Services (DHHS) 
regulations and NIH policies. The Data and Safety Monitoring Committee (DSMC) is responsible 
for conducting Quality Assurance audits on Knight approved protocols according to the Data 
and Safety Monitoring Plan, policies and procedures.  Locally initiated observational and low 
risk interventional studies may be audited by an OHSU Knight DSMC audit team any time after 
enrollment begins. The Quality Assurance audit process provides assurance that the reported 
data accurately reflects the data in the primary patient record and that regulatory requirements 
are met.   
19.1 Monitoring Plan: 
This study represents a moderate risk to study participants because it is a clinical trial involving 
human subjects. Though physical activity and exercise may be associated with adverse events 
(e.g. tiredness, muscle soreness, muscular injury, cardiac events, shortness of breath), most such 
events are associated with inappropriately vigorous exercise, which is not the objective of this 
study.66 The study will be wholly overseen by the OHSU NCI-designated Cancer Institute for both 
safety and compliance to institutional and NCI policies. The PI is responsible for evaluating each 
adverse event as it occurs and for notifying the OHSU IRB of the occurrence of an adverse event 
according to IRB protocols. An interim safety/efficacy review will occur early in the intervention 

 
29 
Protocol Version 21.0 – 05/17/2024 
period to determine potential safety concerns or benefits of the intervention well before the total 
sample has been accrued. The interim safety review will be overseen by OHSU Knight Data 
Safety and Monitoring Committee (DSMC, see details below) and will occur after the first 50 
enrolled couples (~25% of total sample) have completed 3 months of exercise training to assess 
early for program safety. The efficacy review will be conducted by an independent monitor, Dr. 
Tomi Mori, a biostatistician and measurement expert in the OHSU Knight Cancer Institute and 
Oregon Clinical Translational Research Institute (OHSU’s CTSA) and not a member of the study 
personnel, after the first 50 couples (100 participants) have completed their first post-intervention 
(6 month) testing appointment. 
 
Adverse events related or possibly related to  exercise sessions (i.e., group exercise classes, 
prescribed home program exercise, and physical performance measurement appointments) will 
be graded according to their significance for severe consequences, such as injury or death, using 
the following grades determined by the OHSU IRB.  
 
Examples of serious adverse events (life-threatening or disabling and requiring medical attention). 
Serious adverse events that may occur during exercise in this study include death and 
cardiovascular events, though these are extremely rare in the absence of significant cardiac 
pathology. 
 
Examples of moderate adverse events (resolve with treatment). Moderate adverse events that 
may occur during exercise include symptoms, such as shortness of breath and orthostatic 
intolerance.  
 
Examples of mild adverse events (do not require treatment). Reports of side effects, such as 
muscle soreness, moderate tiredness while exercising, and similar discomforts are mild adverse 
events. 
 
Examples of unexpected adverse events that do not include physical harm. Adverse events can 
also include breaches of confidentiality, emotional harms, or complaints about study procedures 
or conduct of investigators.  
 
In this study we do not anticipate moderate or serious adverse events. Only moderate and serious 
adverse events that are related or possibly related to exercise sessions (i.e., group exercise 
classes, prescribed home program exercise, and physical performance measurement 
appointments) will be reported on our Adverse Events Log. 
 
A survey (Adverse Events Survey) was created by the study team to be adminstered monthly 
during the participants’ year long participation in the study. Adverse events reported through this 
survey may be followed-up by study staff with a phone call, e-mail, or in person in class during 
the intervention period, when participants self-report that their reporting condition is due to a 
study-related exercise activity or if more information is needed to determine reportability. 
Participants will also have the opportunity to report adverse events during exercise class, the 
home-program phone calls, or at physcial performance measurement appointments. 
 
19.2. Plan for Reporting Adverse Events 
Serious adverse events will be reported immediately to the Principal Investigator (PI), who will 
immediately notify all other investigators. The PI will file a full written report to the OHSU 
Institutional Review Board (IRB) within 24 hours of notification of the serious event, as required 
by the OHSU IRB. Specifically, the following will be reported, in writing: 1) all deaths in study 

 
30 
Protocol Version 21.0 – 05/17/2024 
participants, during the intervention period, regardless of cause, 2) all serious adverse events 
associated with the study procedures 
 
Moderate adverse events will be tabulated by the PI, who will notify members of the research 
team if trends are identified. If trends are noted, preventive measures will be implemented, such 
as providing education of participants in the study to emphasize prevention of the adverse event. 
Moderate adverse events will be included in annual reports to the OHSU IRB. 
 
Mild adverse events will not be formally logged but, participants will receive advice on avoiding 
such events. 
 
Unexpected adverse events that do not include physical harm, usually having to do with study 
procedures, will be reported within 10 days to OHSU IRB, using a written report form. 
 
Adverse events will be reported to NIH according to NIH protocols. 
19.3. Guidelines to Stop the Study 
Cardiac events or deaths are very rare in persons engaging in low or moderate intensity exercise, 
though it is possible that a person with previously undisclosed cardiovascular disease may 
experience a cardiac event or death during exercise. Regardless of cause, we are required to 
notify the OHSU IRB within 24 hours if a participant dies during this study. We will stop the study 
if the IRB instructs us to do so. 
 
19.4 Data Safety and Monitoring Committee 
The OHSU Knight Cancer Institute Data and Safety Monitoring Committee (DSMC) is 
responsible for overall coordination of all aspects of the DSMP. The internal audit team 
conducts quality assurance audits on all open clinical trials that are not monitored by another 
source. The DSMC meets once each month to review the audit team’s progress and findings 
and to review significant adverse events (SAE) and/or unanticipated problem (UP) reports, and 
Interim Analysis reports. The DSMC also reviews a full report of study activity for all local, active 
clinical trials at the time of continuing review submission including: 
• 
protocol amendments, revisions, consent form revisions 
• 
interim analysis results 
• 
protocol violations 
• 
total number of patients enrolled on-study as compared to expected numbers 
• 
dates of patient enrollments 
• 
vital and study (on or off-study) status of each patient 
• 
all Unanticipated Problems submitted (including dates, description and relationship)  
 
Members receive this information approximately one week prior to Committee meetings, to 
allow for preliminary study and review. The Committee will vote to approve, conditionally 
approve (enrollment may continue after satisfactory response by the principal investigator to 
DSMC is received), suspend or close each protocol reviewed. The Committee decision will be 
documented in monthly meeting minutes. Principal investigators may appeal the decision to the 
Director of the Cancer Institute. 
  
The DSMC oversees the process of serious adverse event reporting to assure that reporting 
requirements are met. The DSMC may require amendments, suspend or terminate any clinical 
trial that falls within its jurisdiction. The DSMC has the authority to report directly to the OHSU 
IRB. The DSMC communicates with and provides semi-annual summary reports to the Knight 
Cancer Regulatory Committee. 

 
31 
Protocol Version 21.0 – 05/17/2024 
  
The DSMC is made up of the following representatives: physician members of OHSU Knight 
Cancer Institute, administrators of Clinical Research Management (CRM), biostatistician, 
research pharmacist, research nurses, and study coordinators. A term of membership is 5 
years. In the event that a Committee member is key personnel (principal investigator, co-
investigator, biostatistician, study coordinator, study investigational pharmacist, study nurse) for 
a study under review, or has any other conflict of interest (including substantial financial interest 
in the study sponsor agency), that member must abstain from Committee review and discussion 
and must leave the room prior to final decisions on the study. In the event that the Chair is the 
principal investigator for the study, the Co-Chair of the Committee will oversee the Committee 
deliberations and final decisions. The Knight DSM Committee includes multiple MD 
representatives as well as an alternate biostatistician for cases in which our primary 
biostatistician has a conflict of interest. 
 
20.0 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN  
No OHSU Knight Cancer Institute study will focus on any particular gender, racial or ethnic 
subset. No subject will be excluded from the study on the basis of gender, racial or ethnic origin. 
Male, female and minority volunteers will be recruited for this study from the general population 
and approximately 50% men and 50% women will be studied. 
The projected gender, racial and ethnic composition of the study will include a higher proportion 
of African Amercian men than state demographics because the prostate cancer 
disproportionately affects African Americans. 
Table 1: Population Demographics - Oregon (%)              
 
Source:   U.S. Census Bureau, 2010    *Totals may not equal 100 due to rounding. 
 
 
Ethnic Category 
Sex/Gender 
Females 
Males 
Total 
Hispanic or Latino 
 
 
11.7 
Not Hispanic or Latino 
 
 
88.3 
Ethnic Category: Total of all subjects* 
 
 
100* 
Racial Category 
 
American Indian or Alaskan Native 
 
 
1.4 
Asian 
 
 
3.7 
Black or African American 
 
 
1.8 
Native Hawaiian or other Pacific Islander 
 
 
0.3 
White 
 
 
83.6 
More than one race 
 
 
3.8 
Unknown/Other 
 
 
5.3 
Racial Category: Total of all subjects* 
 
 
100* 
TOTALS 
50.4 
49.6 
100* 

 
32 
Protocol Version 21.0 – 05/17/2024 
Table 2: Projected Accrual for the Present Study  
Ethnic Category 
Sex/Gender 
Females 
Males 
Unknown 
Total 
Hispanic or Latino 
34 
34 
 
68 
Not Hispanic or Latino 
260 
260 
 
520 
Unknown 
 
 
 
 
Ethnic Category: Total of all 
subjects* 
294 
294 
 
588* 
Racial Category 
 
American Indian or Alaskan Native 
4 
4 
 
8 
Asian 
11 
11 
 
22 
Black or African American 
5 
5 
 
10 
Native Hawaiian or other Pacific 
Islander 
1 
1 
 
2 
White 
246 
246 
 
492 
More than one race 
11 
11 
 
22 
Unknown 
16 
16 
 
32 
Racial Category: Total of all 
subjects* 
294 
294 
 
588* 
 
Source:   Adapted from U.S. Census Bureau, 2010    *Totals may not equal 100 due to rounding. 
 
Table 3: Projected Accrual for Ancillary Study  
 
Ethnic Category 
Sex/Gender 
Females 
Males 
Unknown 
Total 
Hispanic or Latino 
4 
4 
 
8 
Not Hispanic or Latino 
26 
26 
 
52 
Unknown 
 
 
 
 
Ethnic Category: Total of all 
subjects* 
30 
30 
 
60* 
Racial Category 
 
American Indian or Alaskan Native 
0 
0 
 
0 
Asian 
1 
1 
 
2 
Black or African American 
1 
1 
 
2 
Native Hawaiian or other Pacific 
Islander 
0 
0 
 
0 

 
33 
Protocol Version 21.0 – 05/17/2024 
Ethnic Category 
Sex/Gender 
Females 
Males 
Unknown 
Total 
White 
25 
25 
 
50 
More than one race 
1 
1 
 
2 
Unknown 
2 
2 
 
4 
Racial Category: Total of all 
subjects* 
30 
30 
 
60* 
Source:   Adapted from U.S. Census Bureau, 2010    *Totals may not equal projected enrollment 
due to rounding. 
 
21.0 
INCLUSION OF CHILDREN  
In accordance with NIH guidelines on the inclusion of children as participants in research 
involving human subjects, children under the age of 18 years must be included in all human 
subjects’ research, conducted or supported by the NIH, unless there are clear and compelling 
reasons not to include them. Therefore, proposals for research involving human subjects must 
include a description of plans for the inclusion of children. 
 
This protocol does not include children for the following reason:  
 
The number of children with these types of cancer is limited  
 

 
34 
Protocol Version 21.0 – 05/17/2024 
 
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