Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04575831 |
| Other study ID # |
HREBA.CC-18-0681 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2019 |
| Est. completion date |
April 30, 2020 |
Study information
| Verified date |
September 2020 |
| Source |
University of Calgary |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background: Evidence supports exercise and nutrition as beneficial for enhancing QOL in
earlier stages of lung cancer; however, there is minimal research of either intervention -
and none with combined interventions - in advanced lung cancer patients. In addition to a
multimodal intervention approach that includes nutrition and exercise, consideration of
advanced cancer care symptom management is crucial for optimizing the potential benefits of
either intervention.
Objectives: Primary outcome measure of this study is feasibility, 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 to be measured is the impact of the
intervention on PROs, including QOL, fatigue and symptom burden, as well as self-reported
physical activity levels and physical function assessed in-person.
Methods: The proposed exercise intervention will include a centre-based group exercise
program plus home-based exercises, and behaviour change support for advanced non-small cell
lung cancer (NSCLC) patients, classified as stage III or IV with self-reported symptom
burden. Eligible participants must be cleared by the health care professionals (HCP) to
engage in mild to moderate levels of physical activity (PA). 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 measure
feasibility and exploratory outcome measures, with an embedded qualitative component to
examine participant perspectives about study tolerability/feasibility of the intervention. A
subset of participants and instructors will be recruited for qualitative interviews using
purposive sampling to achieve maximum variation based on factors that may lead to different
viewpoints (e.g., age, gender, lung cancer type/stage, treatment).
Relevance: The proposed work will inform the design of a future pragmatic trial for this
population. The goal is to build a patient-focused model of care that delivers wellness
resources for advanced lung cancer care that will ultimately improve the patients' health and
QOL. This approach is novel, patient-focused, and will build a tailored approach within
existing resources to deliver optimal care.
Description:
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
This pilot study will examine a multimodal intervention, including exercise and nutrition in
conjunction with palliative symptom management, on the 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).
Methodology:
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).
We will recruit n=10-15, and based on current patient numbers, this is a conservative
expectation for the 6 month recruitment period.
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. 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 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 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.
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. To reduce burden in this feasibility study, participants will not be required to
report objective physical activity from the device.
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.
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.
