Telephone Support for Advanced Gastrointestinal Cancer Patients and Their Family Caregivers
Phase: NA
Conditions: Gastrointestinal Neoplasms
Sponsor: Indiana University

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Telephone Support for Advanced Gastrointestinal Cancer Patients and 
Caregivers 
NCT04010227 
6/9/2020 
 
 
 

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IUSCC-0703 
Telephone Support for Advanced Gastrointestinal 
Cancer Patients and their Family Caregivers 
 
Principal Investigator: 
Catherine E. Mosher, Ph.D. 
Associate Professor 
IUPUI School of Science 
Department of Psychology 
402 North Blackford Street, LD 124 
Indianapolis, IN 46202 
 
Co-Investigators: 
Victoria L. Champion, Ph.D., R.N., F.A.A.N., Distinguished Professor 
Department of Environments for Health 
School of Nursing/Indiana University 
 
Kurt Kroenke, M.D., Professor 
Department of Medicine 
School of Medicine/Indiana University 
 
Shelley Johns, Psy.D., HSPP, ABPP, Assistant Professor 
Department of Medicine 
School of Medicine/Indiana University 
Center for Health Services Research, Regenstrief Institute 
 
Bert O’Neil, M.D., Professor 
Department of Medicine 
School of Medicine/Indiana University 
 
Patrick Loehrer, M.D., Distinguished Professor  
Department of Medicine 
School of Medicine/Indiana University 
 
Paul Helft, M.D., Professor 
Department of Medicine 
School of Medicine/Indiana University 
 
Ahmad Al-Hader, M.D., Assistant Professor 
Department of Medicine 
School of Medicine/Indiana University 
 
Marianne Matthias, Ph.D., Associate Professor 
Department of Communication Studies/IUPUI 
Roudebush VA and Regenstrief Institute 

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Support Provided by: 
National Cancer Institute 
 
 

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TABLE OF CONTENTS 
 
 
1.0 
Background & Rationale .......................................................................... 5 
2.0 
Study Objectives ...................................................................................... 6 
2.1 
Primary Objective. ........................................................................................ 7 
2.2 
Secondary Objectives .................................................................................... 7 
2.3 
Exploratory Objective .................................................................................... 7 
3.0 
Outcome Measures/Endpoints ................................................................ 7 
3.1 
Primary Outcome Measures ........................................................................... 7 
3.2 
Secondary Outcome Measures ....................................................................... 7 
4.0 
Eligibility Criteria ..................................................................................... 8 
4.1 
Patient Inclusion Criteria ................................................................................ 8 
4.2 
Patient Exclusion Criteria ................................................................................ 8 
    4.3    Caregiver Inclusion Criteria…………………………………………………………..7 
   4.4    Caregiver Exclusion Criteria…………………………………………………………..8 
5.0 
Study Design ............................................................................................ 9 
6.0 
Enrollment/Randomization ................................................................... 10 
7.0 
Study Procedures ................................................................................... 11 
8.0 
Reportable Events .................................................................................. 22 
9.0 
Data Safety Monitoring .......................................................................... 22 
10.0   Study Withdrawal/Discontinuation ....................................................... 24 
11.0 Statistical Considerations ...................................................................... 24 
12.0 Statistical Data Management ................................................................ 26 
13.0 Privacy/Confidentiality Issues .............................................................. 26 
14.0 Follow-up and Record Retention ........................................................... 26 
15.0 References ............................................................................................. 27 
16.0 Appendices ............................................................................................. 32 
 
 
 
 
 
 
 

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1.0 Background & Rationale 
 
Gastrointestinal (GI) cancers are among the most common cancers in the United States, and 
the majority are discovered at advanced stages.1 Fatigue is a highly prevalent symptom in 
advanced GI cancer patients, with up to 68% reporting moderate to severe fatigue.2, 3 
Furthermore, when asked to rank symptoms and concerns, fatigue was the top concern for 
62% of advanced colorectal cancer patients.4 Fatigue often co-occurs with a number of other 
symptoms and substantially impacts daily activities and quality of life (QoL).3, 5-8 Among 
advanced cancer patients, fatigue and related symptoms have been linked to prolonged 
hospitalizations and readmissions.9 In our pilot work with advanced GI cancer patients (N=51), 
67% reported moderate to severe difficulty initiating activities due to fatigue. 
 
Treatments for fatigue have limited empirical support in advanced cancer,10-12 
leading to a critical unmet need for fatigue management in advanced GI cancer 
patients.3, 4 A Cochrane meta-analysis evaluated randomized controlled trials (RCTs) of 18 
pharmacologic treatments for fatigue in patients with advanced cancer and other late-stage 
chronic diseases.10 Given the limitations of the evidence (e.g., small, heterogeneous samples) 
and minimal effect sizes in many trials, the authors did not make recommendations for fatigue 
treatment in these populations. Another Cochrane meta-analysis of 14 behavioral interventions 
for fatigue in advanced cancer, most of which were cognitive-behavioral and supportive-
expressive therapies, drew similar conclusions.12 Of note, only two intervention trials had a 
fatigue eligibility criterion. 
 
As fatigue and related symptoms interfere with patients’ daily functioning, family caregivers 
often assume a range of new responsibilities.13-16 Our team found that among family caregivers 
of advanced GI cancer patients (N=50), 48% reported that they did not have enough time for 
themselves due to caregiving, and 76% reported moderate to severe stress due to balancing 
caregiving with other work and family obligations. Both of these reports and global caregiving 
burden were associated with reduced mental QoL, including symptoms of anxiety and 
depression (rs = -.30 to -.66). Similarly, in population-based research, cancer caregivers 
reported greater activity impairment and worse QoL than non-caregivers.17 
 
Evidence-based interventions to reduce family caregiver burden in advanced cancer 
are lacking. Most behavioral interventions for cancer caregivers have been delivered to 
patient-caregiver dyads coping with early-stage breast or prostate cancer and did not have a 
symptom or distress criterion for study entry.18-20 These interventions yielded small to medium 
effects on caregiver burden and QoL.18-20 In addition, the limited RCTs with advanced cancer 
patient-caregiver dyads generally did not target those at greater risk for poor outcomes (e.g., 
those with high symptom interference with functioning or caregiving burden).21-23 Thus, the 
generalizability of research findings to subgroups most in need of intervention has yet to be 
determined. 
 
The significance of this trial is strengthened by the use of Acceptance and 
Commitment Therapy (ACT), a theory-driven behavioral approach,24 to address 
fatigue interference with functioning in advanced GI cancer patients and caregiver 
burden. The goal of ACT is to increase psychological flexibility so that unwanted internal 
experiences (e.g., physical symptoms, feelings, thoughts) interfere less with meaningful 
activities.24, 25 Psychological flexibility is defined as fully experiencing the present moment while 

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persisting in actions aligned with personal values.24 ACT has a strong evidence base in chronic 
pain26, 27 and mental health.28, 29 A meta-analysis of 39 RCTs found that ACT was superior to 
control conditions for somatic symptoms (effect size [ES]=.58), anxiety/depression (ES=.37), 
and other mental disorders (ES=.92), representing a moderate to large treatment effect.29 ACT 
has not been tested in caregivers of adults, with the exception of one RCT for dementia 
caregivers with high depressive symptoms.30 In this trial, ACT led to similar or better mental 
health outcomes than cognitive-behavioral therapy (CBT). 
 
ACT has also produced promising findings in pilot trials with cancer patients.25, 31-33 
In one trial, late-stage ovarian cancer patients were randomly assigned to 12 in-person sessions 
of ACT or 12 in-person sessions of CBT.33 ACT participants showed large and significantly 
greater improvement in general distress (d = .89), global QoL (d = 1.35), anxiety (d = 1.26), 
and depressive symptoms (d = 1.69) than CBT participants over the intervention period. 
Notably, all attrition was due to death or beginning hospice; thus, ACT appeared to be feasible 
and acceptable to patients. Other pilot feasibility trials of ACT in cancer have also found positive 
changes in psychological outcomes.25, 31 For example, Feros and colleagues tested a 9-session 
ACT intervention for distressed patients with various cancers.25 General distress, mood, and 
global QoL significantly improved immediately post-intervention and three months later 
compared to baseline. Effect sizes for general distress and mood were large, and the effect size 
for global QoL was medium. These pilot data suggest that ACT warrants further study in cancer. 
Indeed, our team extended prior pilot studies by using telephone-based ACT to target fatigue 
interference and related outcomes in 47 MBC patients.34 The intervention showed strong 
evidence of feasibility and promise with respect to fatigue and sleep interference relative to an 
education/support condition. Regarding feasibility, the majority (64%) of patients who could be 
reached via phone were screened for eligibility, and 100% of eligible patients consented. 
Additionally, retention was good with 83% of the entire sample completing the 8-week follow-
up, and 79% completing the 12-week follow-up. Fatigue interference showed moderate 
reduction across time in the ACT group and minimal change in the education/support group; 
the between-group effect size was -.30 at 12 weeks. Furthermore, when examining the 
subsample (n = 24) with moderate to severe fatigue interference at baseline, the between-
group effect size was -.59 at 12 weeks. ACT participants also showed decreased sleep 
interference at 12 weeks, with a between-group effect size of -.40 in the full sample and -.61 in 
the subsample with moderate to severe fatigue interference. Differences between study 
conditions were not significant; however, because it was a pilot study, we focused our analyses 
on effect sizes rather than statistical significance. 
 
ACT can be widely disseminated to clinicians who care for advanced GI cancer 
patients and caregivers. Training in ACT is widely available and accessible to clinicians with 
various professional backgrounds, levels of education, and theoretical orientations. 
Furthermore, rather than being a fixed set of specific techniques, ACT draws from a broad 
range of traditional behavior therapy approaches as well as those outside the behavioral 
tradition (e.g., acceptance, mindfulness, identification of personal values).24, 35 Thus, ACT is an 
adaptable approach that can be delivered as a stand-alone therapy and/or integrated into 
existing therapeutic approaches. 
 
2.0 Study Objectives 
 

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Building on patient-focused ACT pilots in cancer,25, 33, 34 this NCI-funded pilot trial tests a novel, 
dyadic telephone-based ACT program for addressing both fatigue interference (i.e., fatigue’s 
negative impact on activities, mood, and cognition) in advanced GI cancer patients and family 
caregiver burden. In order to enhance translation to geographically dispersed individuals and 
those with high symptom burden or functional impairments, we will deliver the intervention via 
phone. Advanced GI cancer patients with moderate to severe fatigue interference and their 
primary family caregivers with significant caregiving burden (N=50 dyads) will be randomized to 
six weekly 50-minute telephone sessions of either (1) ACT or (2) education/support. ACT 
includes acceptance and mindfulness meditation exercises, identification of personal values, and 
engagement in activities consistent with these values. Examples of dyadic intervention 
components include joint mindfulness practices and having each participant describe the other 
person’s strengths and resources for goal achievement. Feasibility will be examined via accrual, 
attrition, and adherence rates, and acceptability will be evaluated using a mixed methods 
approach (qualitative and quantitative). Outcomes will be assessed at baseline, 2 weeks post-
intervention, and 3 months post-intervention. Findings will inform an R01 application to conduct 
a large-scale RCT of intervention efficacy. The study objectives are: 
 
2.1 Primary Objective: To evaluate the feasibility and acceptability of delivering 
telephone-based ACT to advanced GI cancer patients and their caregivers.  
 
2.2 Secondary Objective: To test the effects of telephone-based ACT on patient 
fatigue interference and caregiver burden (primary outcomes) as well as patient 
sleep interference and patient and caregiver engagement in daily activities, 
progress in value-based living, psychological flexibility, and QoL (secondary 
outcomes). 
Hypothesis: ACT will lead to improved primary and secondary outcomes as compared to 
education/support. 
 
2.3 Exploratory Objective:  
To explore the effects of telephone-based ACT on patient and caregiver physical and 
mental health service use (tertiary outcomes). 
 
3.0   Outcome Measures/Endpoints 
All outcomes will be assessed at baseline, 2 weeks post-intervention, and 3 months post-
intervention (see Table 1 of section 5.0 for complete timing details and assessment windows).  
 
3.1 Primary Outcome Measures:  
The primary outcome measure for patients is the 7-item Fatigue Interference subscale of the 
Fatigue Symptom Inventory (FSI).36, 37 The primary outcome measure for caregivers is the 12-
item short form of the Zarit Burden Interview,38, 39 which evaluates caregiving burden (i.e., 
personal strain and role strain due to caregiving). 
 
3.2 Secondary Outcome Measures: 
(1) 
Patient sleep interference will be assessed with the 8-item Patient-Reported 
Outcomes Measurement Information System (PROMIS) sleep-related impairment 
measure.40, 41 This measure assesses the perceived interference of sleep problems 
with activities, mood, and cognition. 

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(2) 
Patient and caregiver engagement in daily activities will be assessed with the 6-item 
PROMIS short-form measure of ability to participate in social roles and activities.42 
The items, which are reverse-coded, measure difficulty engaging in social and 
recreational activities as well as usual work (including housework).  
(3) 
Patient and caregiver progress in value-based living will be assessed with the 5-item 
Value Progress subscale of the Valuing Questionnaire.43 
(4) 
Patient and caregiver psychological flexibility will be evaluated with the 7-item 
Acceptance and Action Questionnaire-II (AAQ-II).44 
(5) 
QoL. Patient QoL will be assessed with the 15-item McGill Quality of Life 
Questionnaire–Revised, which was designed for patients with life-threatening 
illnesses.45 Caregiver QoL will be assessed with the 10-item PROMIS measure of 
global health.46 
 
4.0 Eligibility Criteria 
 
4.1 Patient Inclusion Criteria: 
 
• 
Patient is at least 3 weeks post-diagnosis of unresectable stage III or stage IV 
gastrointestinal cancer (i.e., anal, colon, esophageal, gallbladder, liver, pancreatic, 
rectal, small intestine, or stomach cancer) and is receiving care at the Indiana 
University Simon Cancer Center or Eskenazi Health. 
• 
Patient is at least 18 years of age. 
• 
Patient has adequate English fluency for study participation.  
• 
Patient is willing to participate in this study. 
• 
Patient has moderate to severe fatigue interference (i.e., mean score >2.5 on the 
Fatigue Interference subscale of the Fatigue Symptom Inventory)36, 37 
• 
Patient has an eligible, consenting family caregiver (see criteria below) 
 
4.2 Patient Exclusion Criteria: 
 
• 
Patient makes 3 or more errors on a validated 6-item cognitive screener47 or exhibits 
significant psychiatric or cognitive impairment (dementia/delirium, intellectual 
disability, active psychosis) that in the judgment of the investigators would preclude 
providing informed consent and study participation. 
• 
Patient Generated Subjective Global Assessment (PG-SGA; the patient-reported 
version of the Eastern Cooperative Oncology Group score) >2.48 
• 
Patient is receiving hospice care at screening. 
• 
Patient does not have working phone service. 
• 
Patient has hearing impairment that precludes participation. 
 
Note: Patients who enroll in hospice during the trial will have the option of continuing trial 
participation. 
 
4.3 Caregiver Inclusion Criteria: 
 
• 
Family caregiver identified by an unresectable stage III or stage IV gastrointestinal 
cancer patient who meets the eligibility criteria. 

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• 
Caregiver lives with the patient or has visited the patient in-person at least twice a 
week for the past month. 
• 
Caregiver is at least 18 years of age. 
• 
Caregiver has adequate English fluency for study participation.  
• 
Caregiver is willing to participate in this study. 
• 
Caregiver has moderate to severe caregiving burden, defined as a score ≥6 on the 
6-item Zarit Burden Interview39 or a T-score >60 (at least one standard deviation 
above the population mean) on the 4-item PROMIS anxiety or depression 
measures.49 
 
4.4 Caregiver Exclusion Criteria: 
 
• 
Caregiver exhibits significant psychiatric or cognitive impairment (dementia/delirium, 
retardation, active psychosis) that in the judgment of the investigators would 
preclude providing informed consent and study participation. 
• 
Caregiver does not have working phone service. 
• 
Caregiver has hearing impairment that precludes participation. 
• 
Patient declines study participation. 
 
5.0   Study Design 
 
The study procedures are shown in Table 1. Advanced GI cancer patients and caregivers (N = 
50 dyads) who meet eligibility criteria and provide informed consent will be randomized to 
receive either six weekly sessions of the ACT intervention or the education/support condition. 
Outcomes will be assessed via telephone at baseline and approximately 2 weeks and 3 months 
post-intervention within the timing windows outlined below.   
 
Table 1 
 
Timing 
Procedure and person(s) responsible 
At least 3 weeks after the patient’s 
advanced GI cancer diagnosis  
(1) The research assistant will contact 
potentially eligible patients, screen patients for 
eligibility, and obtain informed consent, which 
can be done verbally over the phone or face to 
face in the outpatient clinics at the IU Simon 
Cancer Center or Eskenazi Health (see 
“recruitment process” below). 
 
(2) The research assistant will contact 
potentially eligible caregivers, screen 
caregivers for eligibility, and obtain informed 
consent, which can be done verbally over the 
phone or face to face in the outpatient clinics 
at the IU Simon Cancer Center or Eskenazi 
Health (see “recruitment procedures” below). 
If the caregiver is not eligible or does not 
consent to participate, then the patient will be 
informed that s/he is not eligible for the study. 

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Target date = about 1 week after 
recruitment of the patient and 
caregiver. The baseline assessment can 
be completed up to 1 month after 
recruitment. 
(3) Patients and caregivers who consent to 
participate will complete a 30- or 25-minute 
baseline assessment over the phone, 
respectively (see “interview procedures” 
below). The interview will be administered by 
a trained research assistant or a trained 
doctoral student in clinical psychology. 
Sessions will occur approximately 1 
week from each other, with the first 
session occurring about 1 week 
following the baseline assessment. 
Participants will have up to 12 weeks 
to complete the 6 sessions. 
(4) Patients and caregivers will participate in 
six, 50-minute telephone-based sessions of 
ACT or education/support. Sessions will be 
administered by licensed mental health 
professionals who are supervised by the PI 
and Dr. Johns who are clinical psychologists. 
Target date = approximately 2 weeks 
after the last intervention session. 
Assessments can be completed as early 
as 7 days prior to this target follow-up 
date or as late as 14 days following the 
target follow-up date. 
(5) Patients and caregivers will complete a 30-
minute assessment over the phone (see 
“interview procedures” below). Assessments 
will be administered by a trained research 
assistant or a trained doctoral student in 
clinical psychology who are blinded to the 
intervention arm. 
Target date = within 2 weeks of the 2-
week post-intervention assessment. 
The qualitative interview can be 
completed as early as the same day as 
the 2-week follow-up or as late as 21 
days after the 2-week follow-up. 
(6) Patients and caregivers in the ACT 
condition will complete a 30-minute qualitative 
phone interview on intervention acceptability.  
The interview will be administered by a trained 
doctoral student in clinical psychology. 
Target date = approximately 3 months 
after the last intervention session. 
Assessments can be completed as early 
as 7 days prior to this target follow-up 
date or as late as 21 days following the 
target follow-up date. 
(7) Patients and caregivers will complete a 25- 
or 20-minute assessment over the phone, 
respectively. Assessments will be administered 
by a trained research assistant or a trained 
doctoral student in clinical psychology who are 
blinded to the intervention arm. 
 
6.0 Enrollment/Randomization 
 
Following baseline assessments, patient-caregiver dyads (N = 50) will be randomly assigned to 
the ACT intervention or education/support condition in a 1:1 ratio using a stratified block 
randomization scheme to balance the groups by patient performance status (Eastern 
Cooperative Oncology Group scores 0 or 1 vs. 2).48, 50 We will stratify randomization by 
performance status because the decision to provide chemotherapy and other cancer treatments 
is often based on performance status.51 Randomization will be performed using a SAS procedure 
routinely employed by the IU Biostatistics Department. The study statistician will create the 
randomization procedure, and the PI will inform study therapists of their assigned patients. 
Other members of the study team will remain blind to participants’ group assignment. All 
patients will be registered with the Indiana University Cancer Center Clinical Trials Office. 
Applicable regulatory documents must be completed and on file prior to registration of any 
patients. 
 

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7.0 Study Procedures 
 
Below, we first provide an overview of the recruitment and consent process followed by a 
description of the assessment and intervention procedures. 
 
Recruitment Process 
IU or Eskenazi Health medical records will be reviewed by collaborating oncologists who are co-
investigators on this study or their authorized representatives to identify patients who may be 
eligible for the study (i.e., patients who are at least 3 weeks post-diagnosis of unresectable 
stage III or stage IV GI cancer) (see Screening form-Appendix S).  
 
The oncologist or authorized representative will introduce the research assistant (RA) by name 
and ask the patient if the RA could speak with them about a research study.  After being 
introduced by the patient’s oncologist or authorized representative, the RA will meet with the 
patient before or after a clinic visit to describe the study as one examining telephone support 
programs for GI cancer patients and their family caregivers. They will meet in a private room 
and patients or caregivers may decline to speak with the RA. Patients will be asked if they have 
a family caregiver or friend who lives with them or has visited them at least twice per week for 
the past month. If multiple family caregivers are identified, patients will be asked if they would 
be willing to draw a circle and divide it based on the amount of caregiving provided by one or 
more family caregivers, indicating whom to designate as the primary caregiver. This approach 
has been used in other research on cancer caregiving.52 Patients with an eligible caregiver will 
then be handed a print brochure (Appendix A), consent form, and authorization form that 
describe the study, including medical information that would be collected (see patient consent 
and authorization forms). After the research assistant provides an overview of the study and 
answers any questions, interested patients will complete a screening assessment. Conducting 
eligibility screenings for symptoms without obtaining patients’ written informed consent has 
been standard practice at IU and other local medical centers for symptom management trials. 
 
The evaluation will begin with the administration of a validated 6-item cognitive screener47 by a 
trained research assistant (Appendix B). Patients with 3 or more errors on this screener will be 
excluded from study participation. Then patients will complete the 1-item Patient Generated 
Subjective Global Assessment (PG-SGA; the patient-reported version of the Eastern Cooperative 
Oncology Group score).48, 50 Those with a score above 2 will be excluded from the study. Next, 
patients will complete the 7-item Fatigue Interference subscale of the FSI.36, 37 Eligible GI cancer 
patients will have a mean fatigue interference score >2.5. In our pilot work, 98% of metastatic 
breast cancer patients meeting this cutoff for fatigue interference at baseline also endorsed 
fatigue severity at least one-half standard deviation above the population mean.  If a patient is 
ineligible for the study, the RA will tell them that they are not eligible, thank them for their time, 
and ask if they have any questions. 
 
If the caregiver is present, s/he will also be provided with the study brochure, consent form, 
and authorization form. After the research assistant provides an overview of the study and 
answers any questions, interested caregivers will complete the 6-item Zarit Burden Interview39 
and the 4-item PROMIS anxiety and depression measures49 (Appendix B). These will be 
completed on paper and responses will not be shared with the patient. Eligible caregivers will 
have a Zarit Burden Interview score of 6 or higher (an established cutpoint for advanced cancer 
caregivers) or a PROMIS anxiety or depression T-score of 60 or higher (at least one standard 

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deviation above the population mean). Caregivers who are eligible for the study and willing to 
participate may be consented face to face in the clinic. If the caregiver is not present, we will 
ask the patient for permission to send the study brochure, consent form, and authorization to 
the identified caregiver. If permission to contact the caregiver is denied, the patient and 
caregiver will be ineligible for the study. For patients who decline to participate in this study, we 
will ask if they would be willing to provide a reason for their decision. With the patient’s 
permission, we will also document their age, gender, and race (Appendix S). Regarding 
ineligible patients, we will also document their age, gender, and race with their permission.  
This information will be obtained solely for the purpose of determining potential sample 
selection biases.  
 
For potentially eligible caregivers who could not be approached in clinic, the research assistant 
will mail an introductory letter (see Appendix C), study brochure (Appendix A), informed 
consent form, authorization, and response option sheet for the phone screen (Appendix B). The 
letter will be signed by the principal investigator, Catherine Mosher, Ph.D. The letter will also 
introduce the research team and describe how the family caregiver will be contacted further 
about the study. Additionally, a phone number to contact the study staff with any questions or 
to express non-interest in study participation will be provided in the letter. All of this information 
should provide caregivers with the opportunity to think about questions they may have 
regarding the study. Within approximately one to two weeks of mailing the introductory letter, 
the research assistant will telephone caregivers to introduce the study and invite them to 
participate (see Appendix D for telephone script). If a potential participant does not answer the 
phone, a brief voicemail will be left (see Appendix D for telephone script). We will speak with 
the potential participant up to 5 times within approximately 1 to 4 weeks after the first phone 
call or a longer period of time if the caregiver requests a call from staff at a later date. At least 
2 weeks following the first voicemail message, we will leave a second voicemail message if we 
have been unable to reach the prospective participant. Thus, we will leave a maximum of two 
voicemail messages.  
 
The research assistant will screen the caregiver for eligibility and obtain informed consent, a 10 
to 15-minute conversation which can be done verbally over the phone or face to face in the 
outpatient clinics at the IU Simon Cancer Center or Eskenazi Health if the caregiver prefers. If 
the caregiver needs more time or wants more information, an appointment to call again to 
obtain verbal consent will be made. If requested, a new consent form and authorization form 
will be either mailed or emailed to them (based on their preference). Each person (patient or 
caregiver) has the option of providing their email address. In the event that we have made 
several unsuccessful phone call attempts to prospective participants, we will mail a letter to 
them indicating that they should contact the study staff if they are interested in discussing the 
study (see Appendix C). For caregivers who decline participation, we will ask if they would be 
willing to provide a reason for nonparticipation as well as their age, relationship to the patient, 
gender, and race (Appendix S). For caregivers who are ineligible, we will also document their 
age, relationship to the patient, gender, and race with their permission. This information will be 
obtained solely for the purpose of determining potential sample selection biases. Should non-
participants decline to answer these questions, we will discontinue all further contact with them. 
If the caregiver declines study participation or is not eligible, then the patient will be informed 
that s/he is ineligible for the study. 
 

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While some patients will be approached in clinic as outlined above, other patients will be 
approached via a mailing and phone calls.  Before sending a study introductory mailing to any 
potentially eligible patients, the project coordinator will discuss with the oncologist co-
investigator if these potentially eligible patients may receive information about the study.  An 
introductory letter signed by the patient’s oncologist and the PI will be sent to notify each 
potentially eligible person about the study (see Appendix C). The recruitment brochure 
(Appendix A), consent form, and authorization form will also be included in the initial mailing 
with the introductory letter.  Any interested patients will be invited to call for more details. The 
letter also will have an "opt out" component; thus, patients who are not interested in the study 
may call or email the research assistant to indicate that they do not wish to be contacted 
further.  
 
A research assistant will call all prospective participants who do not opt out within 
approximately 1 to 2 weeks after the letter is mailed. The research assistant will describe the 
study, review the consent and authorization forms, and ask if they would like to participate (see 
Appendix D for telephone script).  During that initial call, interested patients will complete the 
screening assessment described above (see Appendix B—screening questionnaires).  The 
research assistant will read the items and response choices aloud and patients will select 
response options.  Those who are interested and eligible will provide verbal consent for study 
participation and verbal authorization to collect information from medical records.  Verbal 
consent was chosen in place of written informed consent to minimize the number of documents 
that link the participant with the research and therefore reduce the risk of a breach of 
confidentiality.  In addition, the entire study will be conducted via the phone. Thus, we do not 
have the opportunity to obtain written consent during a face-to-face meeting with the patient.  
If a potential participant does not answer the phone, a brief voicemail will be left only once (see 
Appendix D for telephone script), and we will only speak with the potential research participant 
up to 5 times within approximately 1 to 4 weeks after the first phone call.   
 
The research assistant will read the entire consent form verbatim and allow the potential 
participant to ask any questions they may have prior to consenting.  In addition, the 
authorization form will be reviewed with the potential participant.  If the patient needs more 
time or wants more information, an appointment to call again to obtain verbal consent will be 
made. If requested, a new consent form and authorization form will be either mailed or emailed 
to them (based on their preference).  
 
During the consent process, patients will be asked if they have a family caregiver who lives with 
them or has visited them at least twice per week for the past month. We will ask the patient for 
permission to send the study brochure, consent form, and authorization to the identified 
caregiver.  If permission to contact the caregiver is denied, the patient will be ineligible for the 
study.  For patients who decline to participate in this study, we will ask if they would be willing 
to provide a reason for their decision. With the patient’s permission, we will also document their 
age, gender, and race. This information will be obtained solely for the purpose of determining 
potential sample selection biases.  Should non-participants decline to answer these questions, 
we will discontinue all further contact with them.  
 
If the family caregiver completes the eligibility screening and is not eligible for the study or 
declines to participate, then the research assistant will ask the patient if there is another family 
caregiver who meets the initial eligibility criteria (e.g., lives with them or has visited them for 

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twice a week during the past month).  With the patient’s permission, the same eligibility 
screening and consent process will be employed with the identified family caregiver.  Up to 3 
family caregivers per patient may be consecutively screened for eligibility.  If none of the family 
caregivers are eligible and willing to participate, then the patient will be ineligible for study 
participation. 
 
Informed Consent Process 
All potential participants will be informed as to their rights as volunteers in a research study and 
will provide informed consent for research participation. The key elements of the informed 
consent procedure which will be explained to prospective participants are: 1) the research 
status of the study; 2) the potential risks and the provisions for them; 3) the lack of guarantee 
of benefit from participation; 4) the voluntary nature of the study; 5) the lack of consequence 
to medical care of the decision to consent or refuse to participate; and 6) the freedom to 
withdraw from the study or to refuse to answer specific questions or to participate in any aspect 
of the study at any time. Consenting patients and caregivers will have the option of providing 
the name and contact information for an emergency contact person who may be contacted in 
the event that the study team repeatedly cannot reach the participant (see Appendix R for 
contact information sheets).  
 
Inclusion of Women and Minorities 
We will recruit advanced GI cancer patients and their primary family caregivers. According to 
American Cancer Society statistics,1 57% of GI cancers are expected to be diagnosed in men in 
2019. Thus, we expect approximately 60% of our patient sample to be male. Evidence indicates 
that the majority of cancer patients’ family caregivers are women;53 indeed in our pilot work, 
66% of caregivers of advanced GI cancer patients were women.54 Thus, we expect 
approximately 65% of our caregiver sample to be female. No racial or ethnic group will be 
excluded from study participation. We will oversample racial and ethnic minorities to generate a 
sample representative of Indianapolis and surrounding areas. Eskenazi Health—one of our 
recruitment sites—sees a highly racially and ethnically diverse patient population. Based on 
recent data from the study sites, we anticipate that the final sample will be approximately 70% 
non-Hispanic White, 20% non-Hispanic Black or African American, 6% Hispanic, and 4% Asian 
or members of other racial/ethnic groups. 
 
Interview Procedures 
Advanced patients and caregivers (N = 50 dyads) who are eligible and provide informed 
consent will complete individual phone assessments at baseline and approximately 2 weeks and 
3 months following the final intervention session (see Table 1 in section 5.0 above for allowable 
assessment windows). The baseline assessment takes about 30 minutes for patients and 25 
minutes for caregivers. Each follow-up assessment takes about 25 minutes for patients and 20 
minutes for caregivers. Interviewers will be blind to study condition. Assessments will include 
questions regarding demographics, medical history, and primary and secondary outcomes. 
Participants will be provided with copies of response options via email or postal mail to facilitate 
survey completion (see Appendix E). Patients and caregivers in the ACT condition will also be 
invited to complete a 30-minute individual qualitative interview about intervention acceptability 
within approximately two weeks of the 2-week follow-up assessment. Each participant will 
receive $40 in Target gift cards via postal mail for each completed assessment (baseline and 2-
week and 3-month follow-ups) for a possible total of $120 in gift cards ($160 in gift cards for 
ACT participants only) for their time. There is no cost to study participants. If we cannot reach 

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a participant for an interview or phone session after several attempts, we will mail them a letter 
asking them to contact the study team (Appendix C). Table 2 below outlines the assessment 
schedule at baseline and the two follow-ups. 
 
ECOG = Eastern Cooperative Oncology Group; FSI = Fatigue Symptom Inventory; PROMIS = Patient- 
Reported Outcomes Measurement Information System; QoL = quality of life. 
 
Study Measures 
Table 2. Quantitative Measures  
 
 
 
Domain 
 
 
 
Measure 
 
 
#  
Items 
 
 
 
Baseline 
 
2-week 
follow-
up 
 
3-month 
follow-
up 
 
Administered to 
Patients (P) or 
Caregivers (C) 
Sociodemographics 
Sociodemographics 
7-8 
X 
 
 
P, C 
Medical comorbidity 
Checklist of 8-9 conditions 
8-9 
X 
 
 
P, C 
Functional status 
Patient-reported ECOG 
1 
X 
X 
X 
P 
Cancer information (e.g., 
date of diagnosis, cancer 
treatments) 
 
 
Chart review 
 
 
n/a 
 
 
X 
 
 
X 
 
 
X 
 
 
N/A 
 
Intervention acceptability 
Intervention acceptability 
scale  
 
6 
 
 
X 
 
 
P, C 
Primary patient outcome: 
fatigue interference 
Fatigue interference 
subscale of FSI 
 
7 
 
X 
 
X 
 
X 
 
P 
Primary caregiver 
outcome: caregiving 
burden 
 
12-item short-form of Zarit 
Burden Interview 
 
 
12 
 
 
X 
 
 
X 
 
 
X 
 
 
C 
Secondary outcomes: 
 
 
 
 
 
 
 
• Sleep interference 
PROMIS short-form sleep-
related impairment 
measure 
 
 
8 
 
 
X 
 
 
X 
 
 
X 
 
 
P 
 
• Engagement in 
daily activities 
PROMIS short-form 
measure of ability to 
participate in social roles 
and activities 
 
 
 
6 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
P, C 
• Progress in value-
based living 
Progress subscale of the 
Valuing Questionnaire 
 
5 
 
X 
 
X 
 
X 
 
P, C 
• Psychological 
flexibility 
Acceptance and Action 
Questionnaire-II 
 
7 
 
X 
 
X 
 
X 
 
P, C 
• QoL 
McGill Quality of Life 
Questionnaire–Revised 
(patients) or PROMIS 
global health measure 
(caregivers) 
 
 
 
15 or 
10 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
P, C 
Tertiary outcomes: 
 
 
 
 
 
 
 
Physical and mental 
healthcare use 
 
 
Healthcare use interview 
 
 
7-8  
 
 
X 
 
 
X 
 
 
X 
 
 
P, C 
Medications  
Medication interview 
n/a 
X 
X 
X 
P, C 
Severity of symptoms: 
 
 
 
 
 
 
 
 
Fatigue severity, sleep 
disturbance, anxiety, 
depressive symptoms, 
pain, and cognitive 
symptoms 
Fatigue severity and 
frequency items from the 
FSI; PROMIS short-form 
measures of sleep 
disturbance, anxiety, 
depression, pain, and 
cognitive function 
 
 
 
 
 
30 or 
37 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
P, C (except that 
pain is only 
assessed in 
patients) 

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Advanced GI cancer patients and caregivers will each complete a 5-minute screening 
assessment to determine eligibility using the measures described below (see Appendix B). 
 
Screening measures: Patients will first complete a validated 6-item cognitive screener.47  
Patients with 3 or more errors on this measure will be ineligible for this study. Then patients will 
complete the 1-item Patient Generated Subjective Global Assessment (PG-SGA; the patient-
reported version of the Eastern Cooperative Oncology Group score).48, 50 Those with a score 
above 2 will be excluded from the study.  Next, patients will complete the 7-item Fatigue 
Interference subscale of the FSI.36, 37 Eligible patients will have a mean score ≥ 2.5, indicating 
moderate to severe fatigue interference. All measures have well-established reliability and 
validity and have been studied in cancer populations. Caregivers will complete the 6-item Zarit 
Burden Interview39 and the 4-item PROMIS anxiety and depression measures.49 Eligible 
caregivers will have a Zarit Burden Interview score of 6 or higher or a PROMIS anxiety or 
depression T-score of 60 or higher (at least one standard deviation above the population 
mean). 
 
Baseline and follow-up measures: Patients and caregivers will complete a baseline assessment 
and two follow-up assessments using the measures described below (see Appendices F-I). The 
baseline assessment takes about 30 minutes for patients and 25 minutes for caregivers. Each 
follow-up assessment takes about 25 minutes for patients and 20 minutes for caregivers. All 
self-report measures have strong evidence of reliability and validity. PROMIS measures were 
tested with over 21,000 people, including cancer patients.55-58 Validated non-PROMIS measures 
will be used for constructs that PROMIS measures do not currently assess (e.g., fatigue 
interference). Patients and caregivers in the ACT condition will also complete a 30-minute 
qualitative interview on intervention acceptability (see Appendix J). Baseline and follow-up 
assessments and qualitative interviews will be audio-recorded so that the PI or a trained 
member of the study team may audit them for adherence to the study protocol. Dr. Matthias, a 
qualitative methodologist, will randomly review at least 20% of qualitative interviews. 
 
Demographic/medical factors. At baseline, patients and caregivers will report standard 
demographics (i.e., age, gender, race/ethnicity, marital status, education, income, employment 
status) and chronic medical conditions.59, 60 Caregivers will also report their relationship to the 
patient. Patients’ cancer information will be collected via chart review (Appendix S).  
 
 
Feasibility and acceptability data. Feasibility will be assessed by accrual rates, attrition, and 
adherence. At the 2-week follow-up, acceptability will be assessed with helpfulness ratings on a 
scale from 1 (did not help at all) to 5 (extremely helpful) for number and length of sessions, 
topics, therapist, and telephone format.54 The RA will be blind to study condition, as the 
questions apply to either condition. For ACT participants, acceptability will also be assessed 
within 2 weeks of the 2-week follow-up via a 30-minute qualitative phone interview on the 
perceived helpfulness and impact of ACT components (see Appendix J for detailed interview 
guide). Qualitative interviews will be conducted with patients and caregivers separately. A 
doctoral student in clinical psychology with qualitative interviewing experience will conduct the 
interviews. 
 
 
Primary outcomes. For patients, fatigue interference will be assessed with the 7-item Fatigue 
Interference subscale of the FSI.36, 37 Items assess the extent to which fatigue in the past week 
interfered with activities, such as bathing, dressing, and housework, ability to concentrate, 

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enjoyment of life, and mood. For caregivers, caregiver burden will be assessed with the 12-item 
short form of the Zarit Burden Interview,38, 39 which evaluates personal strain and role strain 
due to caregiving. 
 
Secondary outcomes. 1) Patient sleep interference will be assessed using the 8-item PROMIS 
sleep-related impairment measure,40, 41 which evaluates the perceived interference of sleep 
problems with activities, mood, and cognition. 2) Patient and caregiver engagement in daily 
activities will be assessed with the 8-item PROMIS measure of ability to participate in social 
roles and activities.42 The items, which are reverse-coded, measure difficulty engaging in social 
and recreational activities as well as usual work (including housework). 3) Patient and caregiver 
progress in value-based living will be measured by the 5-item Value Progress subscale of the 
Valuing Questionnaire.43 This subscale assesses progress in living consistently with personal 
values. 4) Patient and caregiver psychological flexibility will be evaluated with the 7-item 
Acceptance and Action Questionnaire-II (AAQ-II).44 5) Patient QoL will be assessed with the 15-
item McGill Quality of Life Questionnaire–Revised, which was designed for patients with life-
threatening illnesses and evaluates physical, existential, and social well-being.45 Caregiver QoL 
will be assessed with the 10-item PROMIS measure of global health, including physical, mental, 
and social well-being.46 
 
Tertiary outcomes. Patients and caregivers will report their physical and mental healthcare use 
in five domains (e.g., ER visits, outpatient visits) in the past 3 months at baseline and over the 
study period.59, 60 These reports of healthcare use were sensitive to change in an R01-funded 
cancer trial.61 At all time points, participants will also report whether professionals referred them 
to support services and whether referred services were received.52, 62 At all time points, 
participants will also report current medications using established methods from prior trials.63, 64 
We will compute the total number of medications at each time point, as this variable had strong 
predictive validity for both healthcare use and costs in older adults over a 1-year period.65 
 
Measures of symptom severity. Symptom severity will be assessed to characterize the sample. 
For both patients and caregivers, fatigue severity and frequency will be measured with six items 
from the FSI,36, 37 and sleep disturbance, cognitive symptoms, anxiety, and depressive 
symptoms will each be assessed with an 6-item PROMIS measure.40, 41, 49, 57, 58, 66 Patients will 
also complete 3-item and 4-item PROMIS measures of pain severity and impact on functioning, 
respectively.58 
   
ACT Intervention Procedures 
Drs. Mosher and Johns developed the ACT manual (see Table 3 and Appendix K), which was 
informed by literature on the experiences of advanced GI cancer patients and caregivers,2, 3, 15, 
67, 68 the ACT model,24, 35 previous ACT trials with cancer patients and other populations with 
physical and mental health conditions,25, 26, 29, 31, 33, 34 and Dr. Johns’s extensive experience 
delivering ACT to cancer patients and caregivers. A licensed therapist will deliver the 
intervention. While the therapist will aim to hold sessions on a weekly basis for 6 weeks, 
participants will have up to 12 weeks to complete the 6 sessions. Patients and caregivers will 
complete sessions 1 and 4-6 together via speakerphone. Sessions 2 and 3 will be delivered to 
patients and caregivers separately. Holding both dyadic and individual sessions will allow the 
therapist to meet the shared and unique needs of patients and caregivers. We adapted ACT to 
the dyad by incorporating joint mindfulness practices and leveraging the relationship during 
discussions. For example, participants will discuss moments of emotional connection with each 

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other as instances of mindfulness and provide encouragement to the other person during goal 
setting. Individual sessions with patients and caregivers will include exploration of personal 
values. In addition, the workability of attempts to avoid fatigue (if a patient) or unwanted 
thoughts and feelings about caregiving (if a caregiver) will be discussed. Thus, the focus of 
individual sessions is shifting from avoidant responses to the pursuit of value-based action 
despite fatigue or perceived caregiving burden. 
According to the ACT model, psychological flexibility is established through the practice of six 
skills.69 Each session has a primary focus on one of the six psychological skills (see Table 3), 
although in-session exercises and home practice generally promote multiple skills 
simultaneously. During the first session, the patient’s and caregiver’s background and coping 
strategies will be discussed, and the concept of mindfulness will be introduced. Patients will 
complete a 3-item version of the FSI, and patients and caregivers will complete a 4-item 
standardized assessment of anxiety and depressive symptoms at the beginning of each session 
(see Appendix L).36, 49 Completion of this assessment will allow the therapist to monitor and 
respond to participants’ fatigue and distress. Paper copies of the questionnaires will be provided 
to participants to facilitate survey completion. Across the six sessions, participants will practice 
various mindfulness exercises, clarify their values, and set specific goals aligned with their 
values. Sessions will also include discussion of patients’ and caregivers’ experiences coping with 
cancer. Each session will include assessing and recording participants’ home practice of 
mindfulness, value-based action, and other skills and will end with a discussion of practice for 
the week ahead. Through skill practice, participants will learn new, adaptive ways to respond to 
unwanted internal experiences (e.g., fatigue, distress). Handouts summarizing the topics of 
each session (Appendix M) and a CD that our team developed to guide mindfulness practices 
will be mailed to participants along with a box of raisins for a mindful eating exercise. 
Participants will also have the option of receiving the mindfulness recordings via an emailed link 
from IU Box. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Education/Support Condition Procedures 
Dyads in the education/support arm will be directed to resources for practical and health 
information and contact information for psychosocial services. Thus, this study tests whether 
Table 3. Summary of ACT Intervention Manual  
Topic (targeted 
ACT model skill) 
Session and Home Practice (HP) Content 
Session 1 (dyadic) 
Introduction to 
Mindfulness 
(Acceptance) 
• Introductions and overview of the intervention 
• Discuss control- vs. acceptance-based strategies for patient fatigue 
management and caregiver coping with emotions about responsibilities 
• Introduce and practice mindfulness (body scan) with therapist 
HP1: Complete questionnaire on consistency of actions with personal 
values;70 practice mindfulness (body scan) daily and one value-based 
goal 
Session 2 (individual) 
Exploring What is 
Most Important to 
You (Values) 
• Practice mindfulness (awareness of the breath) with therapist  
• Clarify personal values with birthday exercise and explore how person 
might choose to respond to fatigue (if patient) or thoughts/emotions 
about tasks (if caregiver) in an adaptive and values-consistent manner 
HP2: Engage in actions in line with values; practice mindfulness 
(awareness of the breath) daily and log what is noticed 
Session 3 (individual) 
Facing Internal 
Experiences 
(Defusion) 
• Practice mindfulness (“leaves on the stream”) with therapist 
• Explore workability of patient/caregiver attempts to avoid or suppress 
unwanted internal experiences (e.g., fatigue, thoughts/emotions about 
caregiving) and how these attempts lead to actions not aligned with 
values and reduced QoL 
• Practice mindfulness (self-compassion exercise) with therapist 
HP3: Write down a valued activity given up due to fatigue (if patient) or 
thoughts/feelings about caregiving and resulting emotions; also write 
down a valued activity that was pursued despite fatigue or caregiving and 
resulting emotions; practice mindfulness (“leaves on a stream”) daily and 
one value-based goal 
Session 4 (dyadic) 
Mindful Awareness 
(Contact with the 
Present Moment) 
• Practice mindfulness (mindful eating of raisin) with therapist 
• Experiential exercise to support patients and caregivers in flexibly 
choosing their focus in the present moment and debriefing with 
reference to fatigue and cancer caregiving  
• Introduce concept of willingness (i.e., flexibly making contact with the 
present moment, including fatigue and thoughts/feelings about tasks) 
HP4: Do two routine activities with greater awareness; practice 
mindfulness (Tracks 1, 2, 3, or 4 on CD) daily  
Session 5 (dyadic) 
Detaching from 
Internal Experiences 
(Self as Context) 
• Practice mindfulness (3-step self-compassion practice) with therapist 
• Exercises to promote observing and detaching from fatigue and 
emotions about cancer or caregiving to cultivate a transcendent sense 
of self from which to observe and accept changing experience 
HP5: Goal setting; practice value-based goal; daily mindfulness practice 
(person’s choice on CD) 
Session 6 (dyadic) 
Taking Steps to Do 
What Matters to You 
(Committed Action) 
• Practice mindfulness (brief body scan exercise) with therapist 
• Recap of skills and what patient and caregiver learned 
• Goal setting around expanding values-consistent behavior into future 
• Termination and next steps in the study 
HP6: Continue written goals 

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ACT is superior to supportive listening and education on medical center and community 
resources, consistent with common interventions in clinical settings. The duration of sessions 
and number and order of dyadic vs. individual sessions will be identical to the ACT condition. A 
similar comparator was used in our ACT pilot trial with metastatic breast cancer patients,34 and 
similar comparison groups have been used in studies with primarily advanced cancer patient-
caregiver dyads.71, 72 A 
licensed therapist will 
deliver the 
education/support 
intervention. Table 4 
provides a summary of 
the topics for each 
education/support 
session, and the manual 
is found in Appendix N. 
While the therapist will 
aim to hold sessions on a 
weekly basis for 6 weeks, 
participants will have up 
to 12 weeks to complete 
the 6 sessions. 
Education/support 
participants will complete 
the same weekly fatigue 
and distress assessments 
as those in the ACT 
condition. Sessions will 
include an orientation to 
the patient’s medical 
center and treatment 
team, education 
regarding common QoL 
concerns and symptoms 
experienced by cancer 
patients, and an overview of medical center and community resources for addressing these 
concerns. Therapists will also describe resources for addressing financial concerns and methods 
of evaluating health information available via the Internet and other modalities. Participants will 
receive handouts on session topics and will be asked to review them as homework (Appendix 
O). ACT concepts will not be discussed. 
 
Training of Therapists and Treatment Fidelity 
Training of therapists will involve didactics, live demonstrations, and role plays developed by the 
PI and her collaborators. All intervention sessions will be audio recorded, and the PI and Dr. 
Shelley Johns (study co-investigator and licensed clinical psychologist) will randomly review 
20% of recorded sessions to ensure fidelity and quality control. The PI will use therapist 
adherence checklists for the ACT and education/support conditions adapted from NIH-funded 
trials with cancer patients (see Appendix P).73 The PI and Dr. Johns will provide ongoing 
supervision of therapists. During individual supervision with therapists, which will occur 
Table 4. Summary of Education/Support Manual  
Topic 
Session and Homework (HW) Content 
Session 1 
(dyadic): 
Orientation to 
medical center 
and treatment 
team; QoL 
• Overview of sessions & orientation to the medical center 
• Overview of QoL and discussion of physical QoL 
• Discussion of educational materials received from the 
healthcare team 
• Overview of treatment team 
HW1: Review handouts on medical center information 
Session 2 
(individual): 
Resources that 
address social 
functioning 
• Review common challenges in social functioning such as 
talking with children and employment issues 
• Contact info for resources to address social challenges 
HW2: Review handouts on resources to address social 
functioning 
Session 3 
(individual): 
Resources that 
address role and 
emotional 
functioning 
• Review common changes in activities 
• General tips on managing the household 
• Review common emotional responses to cancer and 
cognitive changes following cancer treatment 
• Contact information for mental health services 
HW3: Review handouts on mental health resources 
Session 4 
(dyadic): 
Resources for 
financial 
concerns 
• Review common financial concerns related to cancer 
and its treatment 
• Contact information for resources to address concerns 
HW4: Review handouts on resources for addressing 
financial concerns 
Session 5 
(dyadic): 
Resources for 
evaluating 
health info 
• Review methods of evaluating health information on the 
Internet and other modalities 
• Discuss resources for evaluating health information 
HW5: Review handouts on resources for evaluating health 
information 
Session 6 
(dyadic):  
Review and 
other resources 
• Review all topics discussed in prior sessions and 
available resources for addressing each topic area 
• Discuss websites for accessing cancer-related info 
HW6: Review handouts summarizing all resources 

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approximately every 1-2 weeks, treatment adherence scores will be provided and treatment 
fidelity issues discussed. Role-plays will be conducted to correct deviations from study 
procedures.   
 
Protection of Human Subjects 
The protocol has several measures to monitor for, respond to, or minimize potential distress or 
anxiety detailed below. However, it is important to place the risk of distress in perspective. 
Based on survey evaluations by cancer patients and caregivers enrolled in other psychosocial 
studies,52, 62 participants should not find the questions or the time requirements of the study to 
be burdensome. In fact, a large proportion of individuals who have participated in similar 
studies have commented that they felt that they have benefited from sharing their experiences 
and taking part in interventions. Thus, the risk of distress is modest and the safeguards detailed 
below should be adequate. 
 
• Study team members will clearly acknowledge the voluntary nature of participation 
and individuals will have the ability to decline further contact from study personnel 
(i.e., to opt out). 
• The research assistant, qualitative interviewer, and study therapists will receive 
training from Dr. Mosher, a clinical psychologist with extensive clinical and research 
experience with medical populations. This training will include ways to identify and 
respond to signs of distress. 
• Participants will be fully informed about the study during the informed consent process 
and instructed to decline to answer any question or to discuss any issues they find 
troubling. If the interviewer feels that the participant is becoming anxious or fearful 
over a question, the interviewer will move on to the next question and document the 
reasoning.  
• We will provide a letter with the principal investigator’s and research assistant’s names 
and phone numbers and instructions to call with questions or concerns.  
• If a participant expresses significant distress (e.g., suicidal ideation) at any point 
during the study, Drs. Mosher or Johns (both clinical psychologists) will assess the 
participant and make an appropriate referral for clinical care if needed. In addition, for 
distressed patients, Dr. Mosher or another study team member will contact the 
referring oncologist to inform them of the patient’s high level of distress. 
Patients will also be encouraged to contact the healthcare team if they experience 
moderate to severe symptoms. 
 
Suicidality Risk Protocol 
If a participant expresses suicidal ideation, our research team will use an evidence-based 
algorithm that was developed in 4 earlier depression effectiveness trials in medical patients74-77 
and was tested in two recent trials in general medical (SCAMP trial)78 and cancer (INCPAD 
trial)60 patients. Evidence supports the utility of this algorithm (Appendix Q).79 By this algorithm, 
participants are classified as minimal, lower, or higher risk. Participants with higher risk of 
suicide according to this algorithm will be considered for emergency detention. The latter 
constitute <2% of participants enrolled in depression trials, and we have a protocol for 
expedited evaluation by a clinical psychologist for the rare participant in the higher risk group, 
also tested in the SCAMP and INCPAD trials. All research personnel will be trained by the PI in 
this protocol.  Specifically, after asking follow-up questions (see Appendix Q), Dr. Mosher or Dr. 
Johns (both clinical psychologists) will review the information the same day to determine the 

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appropriate course of action.  If they believe that the participant is in immediate danger of 
harm, they will report it, potentially to authorities including the police.  If the participant is not 
receiving mental health services, then they will be referred to mental health services at a 
location convenient to them. 
 
8.0 Reportable Events 
 
All contact with the participant will be documented beginning at the consent process through 
completion of the study. All documentation will be reviewed regularly. Any events that might 
indicate increased participant distress or anxiety will be promptly brought to the attention of the 
PI and reported to the IRB and DSMC per reporting guidelines listed below. We will promptly 
report to the IRB any instances of consent withdrawal due to distress or anxiety. The IRB will 
be informed at least annually of our data and safety monitoring, summary of participant status, 
and any changes in the risk of the study. 
 
Reporting to the IRB:  
1. Unanticipated problems involving risks to subjects or others will be reported promptly to the 
IRB if they:  
• 
are unexpected; 
• 
are related or possibly related to participation in the research; and 
• 
suggest that the research places subjects or others at a greater risk of harm than 
was previously known or recognized. 
 
If the serious adverse event does not meet all three (3) criteria listed above, the event does not 
have to be promptly reported to the Indiana University IRB. However, it should be reported at 
the time of continuing review. 
 
2. Prompt reporting of unanticipated problems to the IRB is defined as within 5 days from 
becoming aware of the event. AEs will be monitored from the time of consent until the person’s 
participation in the study has ended. 
 
Reporting to the IUSCC Data Safety Monitoring Committee:  
Regardless of study sponsorship, the study team must enter all initial and follow-up SAE, 
expedited, and noncompliance reports into OnCore® for review by the DSMC chair and/or 
coordinator. Expedited reports may include IRB Prompt Report Forms and additional SAE forms 
as required by the sponsor. When follow-up information is received, a follow-up report should 
also be created in OnCore®. This DSMC reporting requirement is in addition to any other 
regulatory bodies to be notified (i.e. IRB, etc.). The DSMC chair and/or coordinator will review 
all SAE, expedited, and noncompliance reports monthly. 
 
9.0 Data Safety Monitoring 
 
This study will be conducted in accordance with the IU Simon Cancer Center Institutional DSMP 
for Low Risk Trials.  
 
Investigators will conduct continuous review of data and subject safety. Quarterly review 
meetings for low risk trials are required and will include the principal investigator, clinical 
research specialist and/or research nurse (other members per principal investigator’s 

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discretion). Quarterly meeting summaries should include review of data, the number of 
subjects, significant toxicities as described in the protocol, and responses observed. Study 
teams should maintain meeting minutes and attendance for submission to the DSMC upon 
request.  
 
Data and Safety Monitoring Committee  
The IUSCC Data and Safety Monitoring Committee (DSMC) is responsible for oversight of 
subject safety, regulatory compliance, and data integrity for this trial. The DSMC will review this 
study annually to review overall trial progress, toxicity, compliance, data integrity, and accrual 
per the Institutional DSMP.  
 
Furthermore, the DSMC conducts an administrative review of serious adverse events (SAEs), 
deviations, reportable events, and any other outstanding business. Major issues may require 
further DSMC review or action.  
 
At any time during the conduct of the trial, if it is the opinion of the investigators that the risks 
(or benefits) to the subject warrant early closure of the study, the DSMC Chair and Compliance 
Officer must be notified within 1 business day via email, and the IRB must be notified within 5 
business days. Alternatively, the DSMC may initiate suspension or early closure of the study 
based on its review.  
 
Study Auditing and Monitoring  
All trials conducted at the IUSCC are subject to auditing and/or monitoring per the Institutional 
DSMP. Reports will be reviewed by the full DSMC at the time of study review.  
 
Data Management/Oncore Reporting Requirements  
The DSMC reviews data and study progress directly from Oncore; therefore, timely data entry 
and status updates are vital. Study data must be entered within Oncore promptly, no later than 
one week from study visit occurrence. Subject status in Oncore will be updated in real time, as 
this may affect overall trial enrollment status. Global SAEs and deviations will be reviewed on a 
monthly basis by the DSMC Chair directly from Oncore.  
 
Study Accrual Oversight  
Accrual data will be entered into the IU Simon Cancer Center OnCore system. The Protocol 
Progress Committee (PPC) reviews study accrual twice per year, while the PPC coordinator 
reviews accrual quarterly.  
 
Oncore Safety Reporting  
In addition to protocol- and regulatory-required safety reporting, all serious adverse events 
(SAEs) will be captured in the Oncore system within 1 business day of notification. Initial SAE 
reporting will include as much detail as available, with follow-up to provide complete 
information. Attributions will be assessed to study drugs, procedures, study disease, and other 
alternate etiology.  
 
Protocol Deviation Reporting  
Protocol deviations will be entered into OnCore within 5 days of discovery and reviewed by the 
DSMC Chair on a monthly basis. Findings will be reported to the full DSMC at the time of study 
review. 

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10.0 Study Withdrawal/Discontinuation 
 
Criteria for removal from the study are as follows:  
 
• Observed severe cognitive impairment that renders continued participation in the study 
impossible, such as confusion or impaired ability to read or to provide accurate answers 
to the interviewer. 
• The patient consents to participate in the study, but their family caregiver declines 
study participation or is not eligible for this study. The patient would no longer be 
eligible to participate in this study, as we are interested in examining data from patient-
caregiver dyads. 
• If the patient or caregiver is no longer able to participate in this study due to death or 
medical factors or decides to stop participation, then the other member of the dyad 
(patient or caregiver) will no longer be eligible to participate in this study.  
• The participant expresses significant distress related to completion of the study (the PI 
will refer the participant to clinical services if needed). 
• The participant provides verbal or written notification that she has decided to 
discontinue study participation. 
• The participant does not follow the study rules (e.g., repeatedly does not answer the 
phone to complete a scheduled interview). 
• Any other reason for which the principal investigator believes the participant should be 
withdrawn. 
 
11.0 Statistical Considerations 
 
Aim 1. Feasibility and acceptability will be evaluated via descriptive statistics for accrual, 
attrition, and adherence as well as Likert-scale items assessing intervention helpfulness. We will 
judge this trial as feasible if: 1) ≥60% of screened eligible dyads enroll in the study;21 and 2) 
≥70% of enrolled dyads complete 5-6 intervention sessions and all assessments. We will judge 
this trial as acceptable if ≥70% of dyads rate ACT as moderately to extremely helpful (i.e., an 
average score ≥4 on 1 to 5 Likert scale items).  
 
To analyze qualitative data on ACT’s acceptability, we will use an immersion/crystallization 
approach.80 Research questions guiding the analysis pertain to the perceived helpfulness of ACT 
components and their impact on functioning and well-being. Interviews will first be transcribed 
by a trained research assistant. Analysis of the interview data will consist of two phases: open 
and focused coding.80, 81 In the open coding phase, the analysts (Drs. Mosher, Matthias, and a 
Ph.D. student in clinical psychology) will independently label each line of data to reflect 
meanings or themes emerging from the text. This is done iteratively, combining, adding, or 
eliminating themes, until analysts agree on a set of emergent thematic categories (codes). In 
focused coding, codes derived in open coding are independently applied to all transcripts. 
Special attention will be paid to negative cases (i.e., data that may call initial observations or 
interpretations into question).82 Transcripts will be divided evenly among analysts, with every 
fourth transcript coded in common to maintain consistency in coding over time. Analysts will 
meet bi-weekly to compare commonly-coded transcripts. Discrepancies will be resolved by 
consensus. Atlas-ti software will facilitate coding, and qualitative results will inform intervention 
refinement. 

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Aim 2. Given that this is a pilot study, our data analytic approach for Aim #2 will be to derive 
effect size estimates rather than test for statistical significance. A linear mixed-model repeated 
measures approach (SAS Proc-Mixed) will be used to examine ACT’s effects on primary and 
secondary outcomes. For outcome measures that only patients or caregivers complete (e.g., 
patient fatigue interference or caregiver burden), models will include main effects of time (as 
categorical) and study group and the time-by-study group interaction. Treatment effects will be 
evidenced by the interaction between time and study group (i.e., group mean differences after 
the intervention but no such differences at baseline). Models will include random intercepts to 
account for nonindependence of individuals’ scores across time. For outcomes reported by 
patients and caregivers (e.g., psychological flexibility), multilevel modeling for dyadic data will 
be used.83, 84 Models will include the main effects of time, study group, and social role (patient 
vs. caregiver) as well as all two and three-way interactions between these variables. The time x 
study group x role interaction will estimate the degree to which treatment effects are different 
for patients and caregivers. Dyadic models will include random intercepts for patients and 
caregivers, as well as the covariance between the intercepts to account for nonindependence 
across time and across partners.  
 
Aim 3. To conduct data analyses for Aim #3, we will use logistic and Poisson regression models 
to explore the effects of ACT on patient and caregiver physical and mental health service use 
(e.g., number of patient ER visits, patient and caregiver use of counseling and/or psychiatric 
medication). Logistic and Poisson regression analyses are appropriate for binary and count 
outcome data, respectively. Analyses will examine study condition as a predictor of health 
service use over the entire study period, controlling for baseline service use. Support service 
referrals will be a covariate in analyses of mental health service use. 
 
Statistical power. Although our analyses focus on effect sizes rather than statistical significance, 
we calculated power for comparing primary outcomes (patient fatigue interference and 
caregiver burden) between study groups. With a sample size of 34 patients and 34 caregivers at 
2 weeks post-intervention (assuming 15% attrition), we will have 80% power (p=.05, two-
tailed) to detect a large intervention effect (d=.99) on either primary outcome in a linear mixed 
model.85 ACT had large effects on distress and QoL outcomes in late-stage ovarian cancer 
patients (ds=.89-1.69) compared to CBT33 and a medium effect (d=-.59) on fatigue 
interference compared to education/support in metastatic breast cancer patients with 
moderate-severe baseline fatigue interference.34  
 
Missing data. All data will be assessed for missingness and multiple imputation with 50 imputed 
samples will be used.86 We will also compare participants and those who decline participation or 
withdraw on demographic and medical factors using t-tests and Chi-square analyses. Further, 
we will carefully track study participation and try to understand the reasons for dropout and 
missing data wherever possible. Identifying potential dropout and missing data mechanisms will 
allow us to incorporate those factors as auxiliary variables for multiple imputation as well as full 
information maximum likelihood estimation method assuming Missing at Random in our future 
Phase II trial.  
 
Potential covariates. T-tests and chi-square analyses will be performed to identify any group 
differences in potential baseline covariates (e.g., demographic and medical variables), and if 
there are differences these variables will be used as covariates. 

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12.0 Statistical Data Management 
 
Primary data will be collected via phone interviews and stored electronically in passphrase 
protected files on the secure Psychology network drive accessed through an encrypted 
computer. Only IRB-approved members of the research team will have access to study files. 
The storage location will be backed up automatically every day. Paper files will be stored in a 
locked filing cabinet in a locked room in the PI’s laboratory. Other data sources include data 
from medical records that will be stored in separate passphrase protected electronic files and 
merged with the primary data as needed. Quality assurance steps will include built in range 
checks. The following quality control methods will be used: 1) single data entry with two 
independent checks of the accuracy of every data point; and 2) discussion of any data entry 
questions with the PI.   
 
13.0 Privacy/Confidentiality Issues 
 
To protect against loss of confidentiality and anonymity, participant data will be identified only 
by a unique identification number assigned to each participant upon enrollment. Except for this 
unique identification number, no other identifying information will appear on the interview 
documents collected during the study. The master file linking the participant names with their 
identification numbers will be stored in a passphrase protected electronic file on a secure 
network drive. Unless required by law, no identifying information will be shared with individuals 
or organizations not affiliated with the study. Regarding individuals who are not eligible for this 
study or decline study participation, their screening information will be stored separately from 
identifying information (e.g., names) and will be kept for auditing purposes for 3 months before 
being destroyed.   
 
Data will be housed on the secure departmental server in Excel and SPSS as well as in Oncore.  
The OnCore® database is a comprehensive, web-based, Clinical Trial Management System 
(CTMS) which utilizes an Oracle database. OnCore® was developed by Forte Research Systems, 
Inc. and is used by the IUSCC Clinical Trials Office and supported by the Indiana Clinical and 
Translational Sciences Institute (CTSI). OnCore® properly used is compliant with Title 21 CFR 
Part 11. OnCore® provides users secure access with unique IDs/passwords and restricts access 
by assigned roles, from any location, to record, manage, and report on data associated with the 
operation and conduct of clinical trials. 
 
Furthermore, all study materials and data will be kept in locked file cabinets in a locked office 
and in passphrase protected electronic files on the secure departmental server. Only project 
members will have access to the files via encrypted computers. Participant identifiers will be 
removed from qualitative interview transcripts. Finally, once data collection has concluded, the 
master file linking participant names with identification numbers will be destroyed. 
 
14.0 Follow-up and Record Retention 
 
Data collection is expected to take place for up to 2 years. Data will be retained for a minimum 
of 7 years in accordance with Indiana State law. Data will be destroyed in the following 
manner: (1) paper will be shredded; (2) computer files will be deleted; and (3) audio-recording 
files will be deleted. 
 

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16.0 Appendices 
 
Appendix A: Study brochure 
Appendix B: Screening questionnaires for patients and caregivers 
Appendix C: Study letters 
Appendix D: Phone script for consenting patients and caregivers 
Appendix E: Response option sheets for patients and caregivers 
Appendix F: Baseline interview for patients 
Appendix G: Baseline interview for caregivers 
Appendix H: Follow-up interviews for patients 

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Appendix I: Follow-up interviews for caregivers 
Appendix J: Qualitative interview protocol for patients and caregivers in the ACT condition 
Appendix K: Manual for ACT intervention condition 
Appendix L: Patient and caregiver questionnaires for ACT and education/support sessions 
Appendix M: Handouts for ACT intervention condition 
Appendix N: Manual for education/support condition 
Appendix O: Handouts for education/support condition for patients and caregivers 
Appendix P: Therapist adherence checklists 
Appendix Q: Suicide screening instrument 
Appendix R: Patient and caregiver contact information sheets 
Appendix S: Screening Form, refuser information, and medical data collection sheets