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Trial registered on ANZCTR


Registration number
ACTRN12614001268639
Ethics application status
Approved
Date submitted
23/11/2014
Date registered
4/12/2014
Date last updated
20/02/2019
Date data sharing statement initially provided
20/02/2019
Date results information initially provided
20/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Benefits of home-based multidisciplinary
rehabilitation in non small cell lung cancer
Scientific title
In people with inoperable non small cell lung cancer, what is the effect of home-based multi-disciplinary rehabilitation compared to usual care, on physical function, symptoms and health related quality of life?
Secondary ID [1] 285725 0
nil
Universal Trial Number (UTN)
Trial acronym
rehabiliTation In lunG cancER - The TIGER trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non small cell lung cancer 293606 0
Condition category
Condition code
Cancer 293893 293893 0 0
Lung - Non small cell
Physical Medicine / Rehabilitation 293894 293894 0 0
Physiotherapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In addition to usual care, participants will receive a structured multidisciplinary intervention including a personalised aerobic and resistance exercise program, goal setting and follow up in one to one phone and home visit consultations and symptom self-care education as outlined below. The aim is to increase general physical function levels, adherence with exercises through behaviour change and symptom management support. The initial physiotherapy session will be performed in the participant’s home, followed by weekly, scripted telephone contact to monitor exercise adherence and progress exercises and up to 2 additional home visits as required. Participants will also receive weekly nursing telephone intervention to monitor symptoms and provide self-care education. At the completion of the eight week home based program, a maintenance exercise program will be prescribed for each participant individually, with monthly physiotherapy telephone contact to monitor adherence and progress to the final 6 month time point.
Physical intervention: Will include both aerobic and resistance exercise training. Exercise intensity for each participant will be guided using a modified Borg Scale for perceived exertion/breathlessness (scale 0-10) aiming for exercise to be performed in the range of 4-5 (somewhat strong exertion). This will permit prescription of the same relative intensity across participants and allow participants to guide and monitor their own exercise effort to minimise likelihood of the exercises being too strenuous. Partners/carers will be encouraged to motivate participants as well as participate in the exercises, diary entry and measurement sessions. Participants will be taught all exercises by trained physiotherapists at an initial one hour face-to-face session.
The resistance exercise package will incorporate upper and lower limb exercises performed in the participant’s home using hand weights. Functional exercises, easy to perform at home, will also be included to assist in strength training (eg; step ups, sit to stand). Exercise dosage will be prescribed following an initial 10RM. With participants completing up to 80% of their 10RM and 2-3 sets of each exercise. Resistance exercises will be performed at least three days per week for 20 minutes and logged into activity diaries. Participants will be provided with a smartphone during the 8-week program and will receive one SMS reminder per day to act as a prompt to complete their exercise regime. They will also be able to use the smartphone to monitor their daily physical activity (steps taken and distance walked). Participants will be provided with a resistance exercise DVD and encourage to view this weekly to remind them of the accurate performance of each exercise.
The aerobic component will consist of prescribed walking exercise. The aim of the walking program will be to progress to walking for a minimum of 150 minutes in total per week at a moderate intensity, as recommended by the guidelines for lung cancer. Walking may be undertaken in bouts of 10 minutes or in one block of 30mins or more. Defined, individualized outdoor physical activity will be prescribed to each subject by the physiotherapist and monitored using a combination of mapping and GPS software. Safety: Participants will be advised not to start exercising if they have a fever (>38 degrees Celsius), or have any new onset chest pain and will be provided with a contact number to ring if they or their partner/carer are concerned. They will be advised to stop exercising if they experience any new chest pains or are too breathless to be able to speak. Participants will be encourage to record details of daily aerobic and resistance exercises into an exercise diary.

Symptom management and behaviour change support sessions: The model used for behaviour change support is the Health Change Australia Model of Behaviour Change. The aim is to build motivation and self-efficacy by identifying and addressing individual barriers to the recommended resistance training and cardiovascular exercise goals and thus initiate and sustain new physical activity behaviours. The physiotherapist will use the behaviour change model to establish the motivation level to participate and set individualised participant goals.
Self-care requirements will be assessed at each 15 minute, scripted nursing telephone session where the nurse will use the validated Edmonton symptom assessment system to identify areas of individual unmet physical and emotional need. The aim of the initial nursing intervention session is to ensure symptoms that might interfere with exercise are addressed. Evidence based self-management information for specific symptoms will be provided to patients during these sessions. In addition, patients will be referred for further assessment and treatment by the medical team if more severe uncontrolled symptoms or side-effects are identified.
Intervention code [1] 290679 0
Rehabilitation
Intervention code [2] 290680 0
Behaviour
Comparator / control treatment
Non-standardised information about the disease, its treatment and side- effects will be provided by the treatment team as per usual practice. All patients, including those allocated to usual care will receive 2 booklets: on lung cancer diagnosis and treatment and exercise for people living with cancer produced by Cancer Council Victoria. Participants will also report (via telephone calls from our research assistant every 4 weeks) their levels of exercise during the intervention.
Control group
Active

Outcomes
Primary outcome [1] 293671 0
Functional exercise capacity (Six minute walk test)
Timepoint [1] 293671 0
9 weeks post baseline assessment
Secondary outcome [1] 311542 0
Physical activity (Sensewear accelerometer worn for 7 days)
Timepoint [1] 311542 0
Baseline, 9 weeks and 6 months post baseline assessment
Secondary outcome [2] 311543 0
Activity motivation (The Behavioural Regulation in Exercise Questionnaire (BREQ-2))
Timepoint [2] 311543 0
Baseline, 9 weeks and 6 months post baseline assessment
Secondary outcome [3] 311544 0
Activity Self–Efficacy (Physical Activity Assessment Inventory)
Timepoint [3] 311544 0
Baseline, 9 weeks and 6 months post baseline assessment
Secondary outcome [4] 311545 0
Muscle strength (quadriceps and hand-grip assessed using hand held dynamometry).
Timepoint [4] 311545 0
Baseline, 9 weeks and 6 months post baseline assessment
Secondary outcome [5] 311546 0
Quadriceps cross-sectional area measured using ultrasound
Timepoint [5] 311546 0
Baseline and 9 weeks post baseline assessment
Secondary outcome [6] 311547 0
Health related quality of life: Functional Assessment of Cancer Therapy- Lung (FACT-L)
Timepoint [6] 311547 0
Baseline, 9 weeks and 6 months post baseline assessment
Secondary outcome [7] 311548 0
Health related quality of life: Assessment of Quality of Life (AQoL)
Timepoint [7] 311548 0
Baseline, 9 weeks and 6 months post baseline assessment
Secondary outcome [8] 311549 0
Psychological distress: Hospital Anxiety and Depression Scale total scale (HADS-T)
Timepoint [8] 311549 0
Baseline, 9 weeks and 6 months post baseline assessment
Secondary outcome [9] 311550 0
Symptom interference: The MD Anderson Symptom Inventory (MDASI-LC)
Timepoint [9] 311550 0
Baseline, 9 weeks and 6 months post baseline assessment.
Secondary outcome [10] 311551 0
Resilience: Connor Davidson Resilience Scale
Timepoint [10] 311551 0
Baseline, 9 weeks and 6 months post baseline assessment.
Secondary outcome [11] 311552 0
Frailty: The Clinical Frailty Scale
Timepoint [11] 311552 0
Baseline
Secondary outcome [12] 311553 0
Cost-effectiveness: health economic questionnaire, MBS/PBS data.
Timepoint [12] 311553 0
9 weeks, 4 and 6 months post baseline assessment
Secondary outcome [13] 311554 0
Physical activity: International Physical Activity Questionnaire (IPAQ-SF).
Timepoint [13] 311554 0
Following completion of the 7 day activity monitoring periods at baseline, 9 weeks and 6 months post baseline assessment.
Secondary outcome [14] 311555 0
Qualitative participant feedback: Semi-structured qualitative interviews including standardised questions will be conducted in a subset of 10 participants from each study arm.
Timepoint [14] 311555 0
baseline and 9 weeks.
Secondary outcome [15] 311556 0
Survival - in addition to collecting this information from hospital medical records a change to the study protocol has been approved by multi-site HREC review to allow us to obtain date and cause of death information from the Registry of Births, Deaths and Marriages for the participants in our study.
Timepoint [15] 311556 0
censored at 3 years post baseline assessment
Secondary outcome [16] 311557 0
Venous blood samples (inflammatory markers)
Timepoint [16] 311557 0
Baseline and 9 week post baseline assessment.

Eligibility
Key inclusion criteria
Inclusion criteria: Eligible patients will have a histologically confirmed diagnosis of inoperable, NSCLC; be scheduled to receive treatment other than surgery (radiotherapy, chemotherapy, targeted therapy); be aged 18 years or older; be able to read and write English; have an Eastern Co-operative Oncology Group performance status of 0-2 and Clinical Frailty Scale score of less than 7 at study entry; have a physician rated estimated life expectancy of greater than or equal to 6 months; have primary attending oncologist approval; have been sedentary in the past month (i.e., patients not performing regular exercise on at least 5 days a week, for at least 30 minutes each session, at a moderate or vigorous intensity for the past month).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if they have: pelvic or lower limb bony metastases, an unstable psychiatric or cognitive disorder; presence of a concurrent, actively treated other malignancy or history of other malignancy treated within the past one year (or three if treatment within the vicinity of the lung fields eg. radiotherapy for breast or oesophageal cancer), other than non-melanoma skin cancer or in-situ melanoma, or have any other comorbidities preventing participation in a land based exercise program.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Potentially eligible participants will be identified through screening clinic lists with eligibility and suitability confirmed by the primary treating oncologist. Participants will be recruited at diagnosis; provide written informed consent; complete baseline assessment and then be randomly allocated. Following informed consent participants will be randomized 1:1 to either the intervention or usual care arms. Randomisation will be remotely and independently performed using random number generation and stratified group allocation will be concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
To ensure randomized groups are similar at baseline, we will stratify based upon cancer treatment type (radical versus palliative). Random order generation will be performed by permuted block randomisation created by computer software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
For the primary outcome (6MWT) our pilot (n=50) variability around the 6MWT change in lung cancer was a standard deviation change of 68m with a deterioration in 6MWT distance of -48m (at 2 months). To maintain (or improve) the 6MWT distance following rehabilitation we will need to recruit 32 participants per group for 80% power at alpha = 0.05 (two tailed). Thus including 30% attrition (pilot data 25%) we need to recruit a total sample of 92 participants.
The analysis will be by intention-to-treat principles: all randomised patients will have data collection until the end of study or they withdraw, and all patients will be included in the analyses. Baseline characteristics will be summarized by group and reported as mean (SD) for normally distributed data, median (IQR) for non-normally distributed data or as proportions. Possible consent bias will be assessed using logistic regression analyses including demographic and clinical variables. Possible differential attrition will be assessed by comparison of two proportions, using chi squared analyses, for those who die or withdraw and those who remain in the study. Analysis of our primary outcome, 6MWT, at two months will be undertaken by two group comparison using either parametric or non-parametric (or bootstrapping) methods depending on assumptions of data. Multiple imputation will be performed to deal with data missing due to loss to follow up and ‘0’ will be assigned for the 6MWT distance where participants are deceased.
For analyses of the 6MWT involving the three time points (baseline, two months and six months) and secondary outcomes, we will use a linear mixed model in which the subject is a random effect, and treatment group and time are fixed effects. Alpha will be set at 0.05 for all analyses and all tests will be two-sided. Data from the questionnaires and semi structured interviews will be collated and summarized. Qualitative data will be transcribed verbatim, entered into a qualitative data management software program and thematic analyses undertaken to identify key barriers and facilitators of physical activity and factors impacting adherence over time. Survival curves will be described using Kaplan-Meier method and compared using stratified logrank tests

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 3199 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 3200 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 3201 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment postcode(s) [1] 8980 0
3052 - Parkville
Recruitment postcode(s) [2] 8981 0
3084 - Heidelberg
Recruitment postcode(s) [3] 8982 0
3002 - East Melbourne

Funding & Sponsors
Funding source category [1] 290299 0
Government body
Name [1] 290299 0
NHMRC
Address [1] 290299 0
GPO Box 1421
Canberra ACT 2601
Country [1] 290299 0
Australia
Primary sponsor type
Individual
Name
Professor Linda Denehy
Address
University of Melbourne
Level 7, 161 Barry St
Parkville
Victoria
3010
Country
Australia
Secondary sponsor category [1] 289009 0
Individual
Name [1] 289009 0
Professor Sanchia Aranda
Address [1] 289009 0
University of Melbourne
Level 6, 161 Barry St
Parkville
Victoria
3010
Country [1] 289009 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292004 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 292004 0
St Andrews Place
East Melbourne
Victoria
3002
Ethics committee country [1] 292004 0
Australia
Date submitted for ethics approval [1] 292004 0
Approval date [1] 292004 0
26/06/2014
Ethics approval number [1] 292004 0
HREC/14/PMCC/27

Summary
Brief summary
The goal of this innovative trial is to test a multidisciplinary home based package of exercise, patient self-management and motivational strategies aimed at improving functional exercise capacity in people with inoperable non-small cell lung cancer (NSCLC). Who is it for? You may be eligible to join this study if you are aged 18 years or above, have a confirmed diagnosis of inoperable NSCLC, are scheduled to receive treatment other than surgery (radiotherapy, chemotherapy, targeted therapy), and do not regularly partake in exercise. Study details Participants in this study will be randomly (by chance) allocated to one of two groups. Participants in one group will receive the intervention package, which comprises 1) a home-based, eight week exercise program including resistance exercises and a walking program and 2) disease self-management education including symptom management and promotion of exercise adherence using behaviour modification strategies with phone follow up. Participants in this group will receive a 1 hour initial home visit from a physiotherapist together with weekly telephone follow-up calls from both the physiotherapist and nurse and up to 2 further physiotherapy home visits if needed. Participants in the second group will receive usual care, which includes 2 booklets: on lung cancer diagnosis and treatment and exercise for people living with cancer produced by Cancer Council Victoria. All participants will undergo assessments of functional exercise capacity, and complete a number of questionnaires at baseline, 9 weeks and 6 months in order to assess quality of life, survival and resource use. This research is clinically based, relevant and aimed at improving the quality of survival of people with NSCLC. The research is designed to be clinically feasible and cost-effective and has the capacity to be widely disseminated and adopted into practice guidelines in this large and vulnerable group.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 53014 0
Prof Linda Denehy
Address 53014 0
University of Melbourne
Level 7, 161 Barry St
Parkville
Victoria
3010
Country 53014 0
Australia
Phone 53014 0
61 3 8344 4171
Fax 53014 0
Email 53014 0
l.denehy@unimelb.edu.au
Contact person for public queries
Name 53015 0
Ms Lara Edbrooke
Address 53015 0
University of Melbourne
Level 7, 161 Barry St
Parkville
Victoria
3010
Country 53015 0
Australia
Phone 53015 0
61 3 8344 5377
Fax 53015 0
Email 53015 0
larae@unimelb.edu.au
Contact person for scientific queries
Name 53016 0
Prof Linda Denehy
Address 53016 0
University of Melbourne
Level 7, 161 Barry St
Parkville
Victoria
3010
Country 53016 0
Australia
Phone 53016 0
61 3 8344 4171
Fax 53016 0
Email 53016 0
l.denehy@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary