The Feasibility of an Exercise and Nutrition Supportive Care (Palliative) Intervention for Advanced Non-small-cell Lung Cancer
Phase: NA
Conditions: Advanced Lung Cancer
Sponsor: University of Calgary

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Study Protocol 
The feasibility of an exercise and nutrition supportive care (palliative) intervention for advanced non-small-
cell lung cancer. 
Advanced Lung Cancer, Exercise, and Nutrition 
August 15, 2019 
NCT ID: NCT04575831 
 

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Exercise, Nutrition and Palliative care in Advanced Lung cancer (ENPAL) Study 
 
Abstract  
 
Background: Cancer treatments can prolong life for those with advanced non-small-cell lung cancer (NSCLC); 
however, it is often at the expense of a multitude of negative symptoms and side-effects that diminish quality 
of life (QOL). Given the complex care needs of this population, a complex intervention must be considered as 
part of an effective approach to supportive care. Evidence supports both exercise and nutrition as beneficial 
for enhancing QOL in earlier stages of lung cancer; however, there is minimal research of either type of 
intervention - and none with combined interventions - in advanced lung cancer patients. We hypothesize that 
a multimodal intervention that includes tailored nutrition and exercise components and behaviour change 
support, along with palliative symptom management, will optimize the potential benefits and ultimately 
improve patient-reported outcomes relating to symptom management and QOL.  
 
Objectives: The primary outcome measure of this pilot study is feasibility, both quantitatively and 
qualitatively, including recruitment (% who participate from those eligible), attendance (weekly group class), 
assessment completion, safety (adverse event reporting), attrition rates, and qualitative themes generated 
from one-on-one participant interviews. The secondary outcome measure is the impact of the intervention 
on patient-reported outcomes (PROs), including QOL, fatigue and symptom burden, as well as self-reported 
physical activity levels and physical function assessed in-person. Data collected from this study will be used to 
inform the design of a future pragmatic clinical trial (PCT) for advanced NSCLC patients. 
 
Methods: The proposed multimodal intervention will include a centre-based group exercise program with 
home-based exercises, as well as individualized nutrition counselling and behaviour change support and 
palliative symptom management, for advanced NSCLC patients classified as stage III or IV with self-reported 
symptom burden. Palliative symptom management will be provided by the Complex Cancer Care 
Management team at the Tom Baker Cancer Centre (TBCC). Eligible participants must be cleared by a clinical 
health care professional (HCP) to engage in mild to moderate levels of physical activity. Using a prospective, 
mixed-methods design (supported by the Medical Research Council guidance for the evaluation of complex 
interventions), the quantitative component of this pilot study will assess feasibility and exploratory outcome 
measures, with an embedded qualitative component to examine participant perspectives and reported 
outcomes about study tolerability/feasibility of the intervention. A subset of participants will be recruited for 
the qualitative interviews using purposive sampling in order to explore their perspectives on the engaging in 
the trial, with a focus on feasibility.  
 
Relevance: The proposed work will expand the “usual” clinical cancer care approach (i.e., a focus on 
symptom management) and provide empirical evidence to support the positive impact of an integrated 
multimodal intervention on QOL and PROs. Specifically, the intervention will combine palliative symptom 
management via the Complex Cancer Management team, with a tailored exercise and nutrition intervention, 
to improve the survivorship experience for patients diagnosed with metastatic and/or nonresectable NSCLC – 
a growing, yet clinically underserved population. The pilot feasibility trial will utilize a mixed methods 
approach to gather quantitative (adherence to interventions, assessment completion rates, adverse events) 
and qualitative (patient perspectives on the intervention tolerability and delivery, facilitators/barriers to 
participation, and overall satisfaction) data that will inform the design of a future PCT for this population. The 
results of this work will contribute to the development of a feasible and patient-focused model of care that 
delivers wellness resources and supportive care with the capacity to improve the QOL and health of patients 
with advanced NSCLC.  
 
 
 

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Background  
 
Lung cancer is the most commonly diagnosed cancer in Canada and is the leading cause of death from 
cancer.1 Despite this, long-term survival rates for lung cancer are improving, owing largely to recent advances 
in treatment. The progression of symptoms of advanced lung cancer often exacerbate the emotional and 
psychological distress experienced by patients and families, which contributes to sedentary behaviour as well 
as diminished QOL.2 In addition, the toxicities of traditional chemotherapies, such as the reduction of lean 
muscle mass3,4,5, are not adequately addressed in current research or used in clinical practice. The proposed 
work will thus assess the feasibility and patient impact of an integrated multimodal intervention for advanced 
(stage III and IV) non-small-cell lung cancer (NSCLC), inclusive of tailored exercise programming, nutrition 
counselling, and behaviour change support, in addition to palliative symptom management.  
 
Evidence shows that physical function and physical independence are among the most important 
determinants of QOL for cancer patients with palliative care needs.6 There is strong empirical evidence to 
demonstrate the positive impact of each individual modality included in the proposed intervention – 
symptom management, nutrition, and exercise – on QOL in advanced cancer populations, including patients 
with metastatic NSCLC.7,8 Nutritional status has been shown to be predictive of QOL in patients with cancer, 
including in those diagnosed with inoperable NSCLC.9  Exercise is also supported as beneficial for overall QOL 
in advanced cancer populations, with particularly strong effects on physical and mental well-being.10  Exercise 
promotes the retention and utilization of nutrients and anabolism, while palliative symptom measures can 
help improve oral intake by ameliorating symptoms such as nausea, mucositis, thrush or constipation.11 
Palliative symptom measures may also help reduce obstacles to exercise, such as pain or dyspnea, that are 
commonly experienced by patients with advanced lung cancer. Despite the promising evidence, few studies 
have examined the effect of combining a nutrition and exercise intervention within palliative care, yet 
preliminary data suggests synergistic effects. Results from a recent randomized control trial  suggest that an 
intervention combining nutrition and exercise components may be feasible in advanced cancer care 
(including stage IV NSCLC care), with an attrition rate of only 86% during the 3-month trial period. 12 While 
this is promising, there is still limited data on the feasibility of these interventions, and there have been no 
RCTs to date that have combined palliative care with nutrition and exercise interventions (Hall CC, Cook J, 
Maddocks M et al. Combined exercise and nutritional rehabilitation in outpatients with incurable cancer: a 
systematic review.  Support Care Cancer 2019; 27:2371–2384) .13,14 
 
Given the growing number of NSCLC patients entering long-term survivorship, this work is critical for ensuring 
that the healthcare system is addressing their unique supportive and palliative care needs. Our project is 
relevant to the present funding opportunity because of its focus on patient reported outcomes (PROs). We 
will utilize PROs that are used in AHS (“Putting Patients First”) and in the cancer population (FACT-G, FACT-
lung, and FACIT-F), and will collect patient feedback (qualitative interviews) on the intervention recruitment 
and delivery. This work will also help connect existing palliative resources at the Tom Baker Cancer Centre 
(Complex Cancer Care team, physiatry, and nutrition), along with ongoing work on the University of Calgary’s 
Alberta Cancer Exercise (ACE) program.15  The preliminary outcome and feasibility data will inform the 
sample size and characteristics for a future PCT. By showing proof of concept in advanced lung cancer, a 
disease with high patient burden, we hope results from this work will facilitate further adaptation of the 
proposed multimodal intervention to support the palliative care needs of other tumour groups. 
 
Research Objectives  
 
a) Objectives and Deliverables: This pilot study will examine a multimodal intervention, 
including exercise and nutrition in conjunction with palliative symptom management, on the 

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QOL of advanced NSCLC patients. The impact of symptom burden on the QOL in NSCLC 
patients is significant and under-recognized. Due to improvements in therapies, there is an 
opportunity to address QOL in this population, whose members are now, on average, living 
longer and potentially more able to engage in rehabilitation interventions. This work will 
address a gap in research and clinical practice by providing initial data that to examine 
delivery of supportive and palliative cancer care to the advanced NSCLC population and 
provide a starting point for tailoring interventions in other tumour groups. Given the novel 
nature of this research, both in terms of the multimodal intervention as well as the focus on 
an underserved population, the primary objective is to assess the feasibility of the 
intervention. Secondary objectives are to obtain preliminary data on patient-reported 
outcomes (PROs) of QOL (FACT-G and FACT-lung), and patient functioning measures 
(symptom measurement, Putting Patients First assessment tool, exercise levels, and fitness 
outcomes). 
b) Methodology: Design: This pilot study will involve a prospective, mixed-methods design. The 
quantitative component includes measures of study feasibility and exploratory outcome 
measures, as described below. The embedded qualitative component will use semi-
structured one-on-one interviews to explore participant perspectives about intervention 
tolerability/feasibility, with a focus on barriers and facilitators to participation, perspectives 
on recruitment, the type and combination of intervention modalities (exercise type, role of 
instructor, and content within the palliative symptom and nutrition intervention), delivery 
locations, duration of the intervention and satisfaction with the outcome measures used. The 
rationale for this study design follows the Medical Research Council guidelines for the 
evaluation of complex interventions16,17 which supports the use of qualitative methods 
nested within a larger trial to understand the “active ingredients” and contextual factors that 
result in certain outcomes in a complex intervention study. This has been used as a 
framework for previously published complex intervention trials in palliative care.18, 19 
Research Team:  Co-Principal Investigators (Culos-Reed and Abdul-Razzak) will share 
responsibility for the research project. Dr. Culos-Reed will coordinate the overall project, as 
well as oversee the exercise component of the intervention. She has 20 years of experience 
working in cancer and exercise research and brings a strong background in knowledge 
translation to the proposed work. Dr. Culos-Reed will also provide in-kind support through 
use of her research facility (Health and Wellness Lab) at the University of Calgary, as well as 
support from current graduate students and staff (CEP, CPTs and research coordinators) 
affiliated with her lab. Dr. Abdul-Razzak will oversee the clinical implementation of the 
project at the TBCC, including support of participant recruitment and delivery of the care by 
the intervention teams. She has extensive training in qualitative methodology and in clinical 
trials research in the palliative population. Several co-applicants and collaborators have been 
instrumental in the conceptualization of this project, and bring extensive clinical expertise in 
oncology (Bebb), cancer physiatry and rehabilitation (Francis, Capozzi) and nutrition therapy 
for patients with advanced cancer (Dexter, Gillis, Walker, Black). This multidisciplinary team 
will continue to be involved in the pilot study design and delivery, as well as subsequent 
work on the PCT. 
Study Participants: Advanced NSCLCA patients, classified as stage III or IV, with self-reported 
symptom burden, and cleared by the health care professionals (HCP) to engage in mild to 
moderate levels of physical activity (PA). Further selection criteria are listed below:  
Inclusion Criteria: 
-Age ≥18 years old 

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-Outpatient at the Tom Baker Cancer Centre (or Holy Cross Centre)  
-Non-small cell lung cancer stages III-IV 
-Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 
-Edmonton Symptom Assessment System (ESAS) score ≥3/10 on any item 
-Hemoglobin level of ≥80g/L as measured within 30 days of enrollment 
-Life expectancy >6 months (as judged by most responsible physician) 
-Screening using the Physical Activity Readiness Questionnaire + (PAR-Q+) for engaging in 
the exercise program 
-May or may not be receiving any form of active cancer treatment (i.e. chemotherapy, 
radiation therapy, immunotherapy or targeted therapy) 
Exclusion Criteria:  
- Active infections at the time of enrollment 
- Enteral tube feeding/parenteral nutrition 
- Mechanical or functional bowel obstruction due to any cause 
- Cognitive impairment 
- Non-English speaking 
- Neuromusculoskeletal issues that impede participation  
 
We will recruit n=10-15, and based on current patient numbers, this is a conservative expectation for the 6 
month recruitment period. This is based on current numbers of advanced cancer patients seen at the TBCC 
(approximately 1900 patients die of advanced cancer annually; Personal communication: Dr. Ayn Sinnarajah, 
Medical Director, Palliative /End-of-Life Care, Calgary Zone.). As this is a pilot study focused on feasibility, 
there is no a priori sample size calculation. A research assistant (RA) will receive electronic alerts of patients 
who score ≥3/10 on any one of the Edmonton Symptom Assessment System (ESAS) “tiredness/ pain/well-
being” items done routinely on all outpatient cancer clinic visits) and contact these patients and their 
oncologists to assess eligibility. After referral from the HCP, potential participants will be screened by the 
Certified Exercise Physiologist (CEP) using the PAR-Q+  to ensure that participation is feasible. Patients 
demonstrating an inability to participate secondary to neuromusculoskeletal issues are ineligible and will be 
referred to a Cancer Physiatrist (i.e., Dr. George Francis) for evaluation and treatment.  
 
A subset of participants will be invited to participate in one-on-one qualitative interviews with the aim of 
understanding their perspectives on engaging in the study, including barriers and facilitators to participation 
and the impact of the interventions of quality of life and symptom control. A thematic analysis approach will 
be utilized, and although an exact a priori sample size cannot be calculated, we estimate that 5-10 interviews 
may be required in order to achieve an adequate understanding of patient perspectives (i.e., data 
saturation). We will use a maximum variation sampling strategy based on age, gender, functional status and 
cancer treatments. Interviews will occur within 2 weeks of the program start, the mid-point (6 weeks) and at 
the end of the intervention (12 weeks) in an attempt to capture the voices of participants who could 
complete the program as well as those who subsequently dropped out before the end of the program. All 
participants will be offered interviews, if they consented to be contacted, and sampling will occur until 
adequate understanding at each timepoint is achieved via the patient perspective. 
Intervention Components:   
1) Exercise: The proposed exercise intervention (under the direction of Drs. Capozzi, Culos-
Reed and Francis) will include a centre-based group exercise program plus home-based 
exercises, along with behaviour change support. The interventionist will be a CEP who will 
receive prior training on the health behaviour change support, similar to that currently used 
within the ACE program.15 The 12-week group-based exercise program, consisting of 1 
weekly 75 minute session, of which 45 minutes are exercise and 15 minutes of yoga, and the 
other 15 minutes includes education and facilitating the group social support, will be 

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delivered in dedicated fitness facilities located at the Holy Cross Hospital in Calgary and at 
the University of Calgary. Forty-five minute exercise circuits will include 6 exercise stations, 
with modifications made according to the baseline physical function of each participant. The 
exercise circuit will be followed by a 15-minute therapeutic yoga class, based on Dr. Culos-
Reed’s Yoga Thrive program.20-22 Overall, the 60 minute session will include a light warm up 
(5-10 minutes), and 6 exercise stations with a range of functional exercises designed to target 
both aerobic and strength components of fitness (35-40 minutes), with modifications made 
according to physical function at the start of the program. The main focus of the circuit will 
be on muscle strength, balance, flexibility and aerobic capacity as associated with beneficial 
daily physical function (i.e., for activities of daily living). Most group sessions will involve a 
series of circuit-style classes, that allow for adequate group supervision as well as the ability 
for individuals to work at their own pace. In addition to the weekly group-based class, a 
home-based exercise prescription for an additional 1-2 sessions per week, facilitated by 
provision of basic home-based fitness equipment and the Yoga Thrive class videos, will be 
provided. A FitBit will also be provided for the duration of the study to support physical 
activity behavior change and enhance safety, and returned upon completion of the exercise 
program. To reduce burden, participants will not be required to report objective physical 
activity from the device.  
2) Palliative Symptom Management: Palliative symptom management (under the direction of 
Drs. Abdul-Razzak and Bebb, and Dr. Lyle Galloway) will focus on symptoms that contribute 
to reduced QOL (e.g. pain, fatigue, nausea), limit one’s ability to engage in exercise, or 
present barriers to oral intake (e.g., pain management, nausea, mucositis, thrush). These will 
be delivered by the Complex Cancer Care Management team at the TBCC, which includes a 
team of physicians, a nurse practitioner, advanced practice pharmacists and a nurse 
coordinator. Clinicians will deliver pharmacologic and non-pharmacologic therapies based on 
their clinical judgement. Participant assessments will occur in conjunction with scheduled 
lung cancer clinic visits, cancer therapy treatment visits, or as separate dedicated research 
visits when necessary. The initial assessment will occur within two weeks of the exercise 
program initiation. After the initial assessment, follow-up consultations can occur at the 
discretion of the palliative care clinicians and participants and may occur either in person or 
by phone. Clinical case report forms will be used to track the type of treatments provided 
during these visits for descriptive purposes.   
 
3) Nutrition: The nutrition component of the intervention is designed to meet individual 
nutrient needs and lifestyle of participants, as well as work synergistically with the previously 
described exercise component. The study coordinator will ask participants to complete a self-
administered online 24-hr dietary food recall. Participants will be asked to record one 
weekday and one weekend day. The Automated Self-Administered 24-hour (ASA24®) dietary 
assessment tool was created by the National Cancer Institute (NCI), and is a free web-based 
tool that enables multiple, automatically coded, self-administered 24-hour recalls 
(http://asa24.ca/ ). Participants will be provided with instructions on how to use this 
technology. Chelsia Gillis (PhD Candidate, RD on the research team) will consult with the 
TBCC Registered Dietitian (RD) team to develop a relevant feedback form and tailored 
nutrition advice based on a pre-study food recall evaluation (“what do you typically eat in a 
day?”).This evaluation will assess micro- and macronutrient intake, as well as individual client 
needs. Data from this evaluation will be analyzed and managed under the leadership of Gillis, 
who will also direct TBCC staff nutritionist on the nutrition intervention delivery within 2 
weeks of study enrollment. RDs involved in the study will also have the ability to recommend 
interventions based on the nutrition assessment feedback form, such as oral nutritional 

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supplementation or target daily protein and caloric intake. The number of follow-up dietitian 
visits will be determined based on individual need for each participant, and post-study food 
recall evaluation data will be collected and analyzed by Gillis (with support from appropriate 
members of the research team) to assess changes in food intake behaviours, and possible 
correlations to levels of exercise participation and patient-reported outcomes. 
Data Collection: We will collect demographic data and details of tumour type (e.g., histology, 
biomarkers) and treatments received prior to and during the trial (e.g., chemotherapy, 
targeted therapy, radiation therapy). Primary outcome measures will assess study feasibility 
both quantitatively and qualitatively, including recruitment (% who participate from those 
eligible), attendance (weekly group class), assessment completion, safety (adverse event 
reporting), attrition rates, and qualitative themes generated from one-on-one participant 
interviews (conducted at the end of the intervention). We will recruit a subset of participants 
for the interviews, using purposive sampling to achieve maximum variation based on factors 
that may lead to different viewpoints (e.g., age, gender, lifestyle factors, cancer stage, 
treatment). It is hypothesized that a weekly group-based PA intervention will be feasible for 
advanced NSCLC patients, (predicted as 30% recruitment of patients approached for 
participation and 60% attendance at weekly group class and 70% assessment completion), 
and safe (zero reported adverse events related to the exercise intervention). 
Secondary outcomes include exploratory analysis of the intervention’s impact on PROs, 
including QOL, including fatigue and symptom burden. QOL will be measured with the FACT-
general and FACT-lung, and fatigue will be measured with the FACIT-fatigue. The symptom 
burden inventory (ESAS) that is part of the Putting Patients First (PPF) assessment is collected 
for all patients at TBCC and will be collected from chart review. It will also be collected before 
and after each exercise session.  Nutrition will be assessed from the food recall evaluation 
data collected pre and post intervention. Physical performance (modified senior’s fitness 
test: resting heart rate, resting blood pressure, height, weight, waist/hip circumference, sit-
and-reach, shoulder range of motion, 30-second sit to stand, handgrip strength, 6-minute 
walk test, single-leg balance), activity levels (self-reported, Godin Leisure Time Exercise 
Questionnaire) and opioid/other drug use (chart review) will be assessed at baseline (pre-
intervention) and post-intervention. To reduce burden in this feasibility study, participants 
will not be required to report objective physical activity from the device. 
PRO measures will be collected through questionnaires administered at baseline (pre-
intervention) and post-intervention and completed either online (survey monkey) or in 
person during the clinic or exercise assessment using a hard copy of the online survey. 
Exercise assessments will be completed at the Health and Wellness Lab (Culos-Reed) by a 
CEP not involved in the delivery of the exercise intervention. Relevant medical or symptom 
management information will be obtained from chart review and from the case report forms 
collected over the duration of the 12-week intervention, and stored in a secure offline 
database. 
Analysis: Quantitative analysis will include descriptive statistics (means/medians, standard 
deviations) and dependent t-tests to measure change over time within the participants. The 
qualitative analysis of the interviews will include verbatim transcription and input into NVivo 
for thematic analysis. Results of both data sources analyses will be examined to provide a 
richer understanding of the feasibility and tolerability of the described multimodal 
intervention in the advanced NSCLC population. 
 
Funding  

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The proposed work will inform the feasibility of providing a multimodal complex care intervention to 
promote QOL in advanced NSCLC patients. Specifically, by evaluating feasibility of this intervention, we aim to 
develop a larger trial (PCT) aimed at measuring the impact of a multimodal cancer rehabilitation service on 
QOL in numerous advanced tumour group populations. Along with ongoing pilot data collection in the 
advanced multiple myeloma population23 and the delivery of exercise to all tumour groups within the ACE 
program, the current data will enhance our understanding of how our standard cancer and exercise program 
(ACE) needs to be tailored, and possibly complemented by nutrition and palliative symptom management, to 
address unique needs of NSCLC patients, and eventually other tumour groups in need of palliative care. In 
addition, utilizing resources available within nutrition services and from the Complex Cancer Management 
team, we aim to deliver a feasible clinic-based supportive care program advanced cancer care. Specifically, 
this pilot work will inform advanced cancer care exercise programming within ACE, as well as the logistics of 
multimodal interventions delivered in the cancer care setting, utilizing nutrition counselling and palliative 
symptom management services. 
 
The compilation of data from these three projects will be used to inform submissions for CCSRI Impact and 
Quality of Life grants (2020), and a CIHR project team grant (September 2020). Given the increased focus in 
cancer survivorship and recognition that tailored interventions must consider the unique needs of differing 
cancer populations, we believe this preliminary work will support our team’s capacity to be successful for 
larger grants, and deliver successful implementation effective palliative programming in clinic-based settings. 
 
Outside of the research impact of this work, the proposed study could have direct impact on how we use 
“putting patients first” symptom burden information to deliver wellness resources that positively impact QOL 
for NSCLC patients. Specifically, this pilot study will provide (a) an understanding of appropriate referral and 
screening procedures prior to intervention delivery, (b) the needs of the clinic HCPs to support referral and 
address their patient needs, and (c) based on PROs and the interviews with patient, an assessment of the 
intervention feasibility and potential benefits. Utilizing a patient-perspective and delivering the intervention 
using existing resources will help to inform future clinical practice and guidelines for more responsive 
advanced cancer care. Despite overwhelming evidence as to potential benefits, wellness interventions such 
as exercise and nutrition are generally lacking across the cancer care pathway. The current work will increase 
the efficacy of the cancer care pathway by collating and contributing evidence to a feasible intervention for 
advanced NSCLC patients. Longer term, we hope to translate the findings from this pilot to other tumour 
groups, working on tailoring referral and screening and best addressing the unique symptom burdens for 
each group by tailoring the interventions to address specific needs.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Unpublished master’s thesis, The University of Calgary, Calgary, Alberta. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Co-Applicant #5 (Last Name, First Name) 
 
Francis, George, MD, FRCPC  
 
Department: 
Physical Medicine & Rehabilitation, Outpatient Clinic, Holy Cross Centre  
 
Email Address: 
George.Francis@albertahealthservices.ca 
 
 
Co-Applicant #6 (Last Name, First Name) 
 
Bebb, Gwyn BMBCh, PhD 
 
Department: 
Tom Baker Cancer Centre 
 
Email Address: 
Gwyn.Bebb@albertahealthservices.ca 
 
 
Co-Applicant #7 (Last Name, First Name) 
 
Black, Jennifer, RD 
 
Department: 
CancerControl Alberta, Alberta Health Services 
 
Email Address: 
Jennifer.Black@albertahealthservices.ca 
 
 
Collaborator #1 (Last Name, First Name) 
 
Walker, Edward, RD 
 
Department: 
CancerControl Alberta, Alberta Health Services 
 
Email Address: 
Edward.Walker@albertahealthservices.ca