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Trial registered on ANZCTR


Registration number
ACTRN12624001032549
Ethics application status
Approved
Date submitted
6/08/2024
Date registered
27/08/2024
Date last updated
24/11/2024
Date data sharing statement initially provided
27/08/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Lung cancer rehabilitation and immunotherapy: a pilot randomised controlled trial.
Scientific title
Feasibility and safety of rehabilitation for people with non-small cell lung cancer being treated with immunotherapy: a pilot randomised controlled trial.
Secondary ID [1] 312191 0
The University of Melbourne CT ID: 29740
Universal Trial Number (UTN)
Trial acronym
UNITE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small cell lung cancer 333860 0
Condition category
Condition code
Cancer 330536 330536 0 0
Lung - Non small cell
Physical Medicine / Rehabilitation 331376 331376 0 0
Physiotherapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The current usual care for people with lung cancer receiving immunotherapy treatment at the recruitment site does not routinely involve referral for rehabilitation services. As part of usual care all participants receive usual care medical services and support from a nurse coordinator.

In addition to usual care, intervention participants will receive a 12-week co-designed rehabilitation program. All intervention participants will attend an initial individual appointment (60-minutes) with a physiotherapist at PMCC or via telehealth. During this appointment the physiotherapist will screen for the need for referral to nutrition and psychology using validated screening questionnaires (Malnutrition Screening Tool [MST] and Patient Health Questionnaire-4 item [PHQ-4]). The MST and PHQ-4 are valid and reliable tools, with scores ranging from 0-5 and 0-12 respectively, and are used to screen for risk of malnutrition and anxiety or depression. Usual care referrals to these disciplines will be made if participants score >3 on either of these tools (indicating they are at risk of malnutrition or anxiety/depression). If participants agree to a psychology referral being made they will be given the option of this occurring by the physiotherapist making the referral to the psychology service at Peter Mac or seeing their GP for a Mental Health Care Plan and referral.

During the initial appointment intervention participants will be prescribed and will complete an aerobic (e.g., treadmill walking, stationary cycling, marching/running on the spot) and strength (functional [e.g., squats, heel raises] or upper limb exercises with resistance bands] exercise program. Exercise prescription will be individualized and progressive, taking into account baseline assessment findings and previous exercise experiences and aim to work towards achieving the exercise recommendations for people with cancer of performing 150 minutes of aerobic exercise and 2-3 strength training sessions per week. Exercise will be initially prescribed at a moderate-intensity ('moderate' to 'somewhat hard' 3-4 on the Modified Borg Scale)

Following the initial appointment participants will be offered supervised group exercise classes (60 minutes for exercise and every second session an additional 30 minutes for education and building social connections), twice weekly for 12 weeks and can choose to attend either in-person, centre-based or telehealth classes. Telehealth classes will use the usual care PMCC platform (HealthDirect) and Zoom. Zoom maintains several robust security standards to maintain privacy and security. Participants will be provided with PMCC usual care resources and supported by trial staff to use telehealth. Participants will also be prescribed a moderate-intensity home walking program and encouraged to complete this, commencing at a minimum of 10 minutes, on up to 3 non-class days.

A second individual face-to-face or telehealth session with the physiotherapist will be offered to participants at approximately 6 weeks to assess that exercises are being performed optimally.

Aerobic exercise (continuous and interval) will include treadmill walking or cycling (centre-based) or marching/running on the spot (telehealth). Initial exercise prescription will be individualized (e.g., based on 80% of the baseline six-minute walk test speed). Exercise intensity for each participant will be guided using a modified Borg Scale for perceived exertion/breathlessness (scale 0-10). At program commencement, the aim is for exercise to be performed in the range of 3-4 (‘moderate’ to ‘somewhat hard’ level of exertion). The resistance exercise package will incorporate upper and lower limb exercises performed using exercise equipment in the centre. Participants will be provided with colour coded elastic energy from Therabands® (elastic resistance bands) to perform strength exercises in telehealth sessions. Resistance training will be prescribed individually to approximate 80% of the 10-repetition maximum (the weight that can be lifted 10 times whilst maintaining the correct technique). The exercise band that requires them to exert moderate force but with which they can maintain control throughout the exercises will be used to commence. Functional exercises will also be included to assist in strength training (e.g., step ups, sit to stand from a chair). Participants will perform 2 sets of 8-10 reps initially at moderate intensity (3-4 on the Modified Borg Scale). Programs will be individually progressed according to American College of Sports Medicine guidelines.

Behaviour change strategies to increase and sustain new exercise behaviours will be incorporated into the intervention, including action plan development, goal setting, and identification of barriers and enablers to exercising. Participants will be provided with an activity monitor (such as a Fitbit device) or use their own device to monitor their daily step counts. The global positioning system (GPS) function will be turned off.

Participants will be educated regarding the safety and benefits of exercise for people with cancer and guided to use the Borg rating of perceived exertion to monitor their exercise intensity. A paper exercise diary will be provided for participants to track prescribed and performed unsupervised home exercise. Additional educational material comprises existing resources which are publicly available regarding management of cancer-related fatigue, eating well, managing breathlessness, side effects of immunotherapy and mental and emotional health. These will be available in printed format and as electronic links available from the study website.

At the completion of the 12-week program, participants will be encouraged to continue exercising in their local communities. To facilitate this transition the intervention physiotherapist will provide monthly telehealth (video or telephone dependent on participant preference) 15-30-minute individual appointments for three months to review progress, modify exercise programs as required and link participants with community resources as needed.
Intervention code [1] 328639 0
Rehabilitation
Comparator / control treatment
The current usual care for people with lung cancer receiving immunotherapy treatment at the recruitment site does not routinely involve referral for rehabilitation services. All participants will receive usual care medical services and support from a nurse coordinator.
Control group
Active

Outcomes
Primary outcome [1] 338298 0
Feasibility (consent rate of eligible participants)
Timepoint [1] 338298 0
Assessed at completion of recruitment
Primary outcome [2] 338299 0
Safety
Timepoint [2] 338299 0
For all participants this will be assessed at baseline (T0), 13-weeks post-baseline (T1) and 6-months post-baseline (T2) follow-up assessments. In addition this will be assessed during the 24 exercise class sessions for the intervention group participants
Secondary outcome [1] 435345 0
Acceptability
Timepoint [1] 435345 0
13-weeks post-baseline (T1) and 6-months post-baseline (T2)
Secondary outcome [2] 435346 0
Intervention fidelity
Timepoint [2] 435346 0
Assessed at completion of the intervention (T1, 13-weeks post-baseline) for each intervention session and at T2 (6-months post-baseline).
Secondary outcome [3] 435347 0
Trial retention
Timepoint [3] 435347 0
Assessed at 13-weeks post-baseline (T1) and 6-months post-baseline (T2)
Secondary outcome [4] 435348 0
Functional exercise capacity
Timepoint [4] 435348 0
Assessed at T0 (baseline) and T1 (13-weeks post-baseline)
Secondary outcome [5] 435349 0
Physical function
Timepoint [5] 435349 0
Assessed at T0 (baseline) and T1 (13-weeks post-baseline)
Secondary outcome [6] 435350 0
Health-related quality of life
Timepoint [6] 435350 0
Assessed at T0 (baseline) and T1 (13-weeks post-baseline)
Secondary outcome [7] 435351 0
Symptom levels
Timepoint [7] 435351 0
Assessed at T0 (baseline) and T1 (13-weeks post-baseline)
Secondary outcome [8] 435352 0
Patient satisfaction
Timepoint [8] 435352 0
T2 (6-months post-baseline)

Eligibility
Key inclusion criteria
• People with a histologically confirmed diagnosis of stage IV, inoperable non-small cell lung cancer (NSCLC) and receiving or are planned to commence treatment with immune checkpoint inhibitors (immunotherapy) either alone or in combination with chemotherapy.
• Age > or = 18 years at screening
• Have provided written informed consent for the trial
• Able to read and write English
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Available for follow up
• Life expectancy greater than 6 months
• Able to access telehealth for exercise classes if that is their preferred method of attending (requires access to a suitable device and internet sufficient for a video call)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Patients scheduled to receive or receiving neoadjuvant immunotherapy or chemo-immunotherapy.
• More than six months post commencement of immunotherapy
• Unstable psychiatric, cognitive or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Concurrent, actively treated other malignancy or history of other malignancy treated within the past year (other than non- melanoma skin cancer or in-situ melanoma)
• Comorbidities preventing participation in land-based exercise
• Have met the exercise guidelines for people with cancer for the past month
• Patients with a documented bone metastasis where the stability poses a risk of injury during the performance of exercise training; as assessed by the treating oncologist or orthopaedic surgeon.
Patients who are admitted to hospital as inpatients and unable to be recruited within 6 months of commencing immunotherapy.

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)
The database administrator or independent statistician will upload the randomisation schedule and randomisation will be implemented through the module within the trial REDCap database. Confirmation of registration/randomisation will be provided electronically as well as by a unique patient identification number for the patient and the assigned randomisation arm.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The group allocation ratio will be 2:1 (intervention group:usual care). There will be no stratification. The randomisation schedule will be remotely and independently generated by a statistician or data manager who is independent of the trial using computerized random number generation.
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
Safety/efficacy
Statistical methods / analysis
Descriptive statistics (including counts and percentages for nominal and crude-scale ordinal (<10 levels) valued variables; and means and standard deviations or medians and interquartile ranges, as appropriate, for continuous valued variables) will be used to summarise participant demographic and clinical characteristics.

SAFETY OUTCOMES
Counts and percentages will be used to summarise data on adverse events. These will be tabulated by severity grade.

FEASIBILITY and ACCEPTABILITY OUTCOMES
Descriptive statistics (including counts and percentages for nominal and crude-scale ordinal (<10 levels) valued variables; and means and standard deviations or medians and interquartile ranges, as appropriate, for continuous valued variables) will be used to summarise trial consent rates, intervention fidelity (adherence operational data on the number of intervention sessions attended and the intervention relative dose intensity) and retention rates at 13-week and 6-month follow-up assessments.

SECONDARY PRELIMINARY EFFECTIVENESS OUTCOMES
Continuous variables include six-minute walk test distance, 30 second sit-to-stand test (number of stands), EORTC QLQ-C30 and ESAS-r. Counts and percentages will be used to summarise missing data, including missing items and forms for patient-reported outcome measures. Patient-reported outcome measures will be scored according to author guidelines. Means, standard deviations, confidence intervals and ranges will be used to summarise continuous outcomes at each time-point by trial arm.

Change over time in secondary preliminary effectiveness outcomes will be assessed with paired samples t tests or the Wilcoxon Signed Rank Test for parametric and non-parametric data respectively dependent on normality of distributions. Responsiveness will be determined by effect sizes which will be calculated for parametric data as Cohen’s d ((mean difference)/(pooled SD)) and for non-parametric data r=Z/vn. All statistical analyses will be exploratory in nature given this is a pilot study and not powered to detect differences between groups for these outcomes.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
10/09/2024
Actual
7/10/2024
Date of last participant enrolment
Anticipated
30/06/2025
Actual
Date of last data collection
Anticipated
24/12/2025
Actual
Sample size
Target
30
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26566 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 42608 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 316567 0
Government body
Name [1] 316567 0
The Victorian Cancer Agency
Country [1] 316567 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 318744 0
None
Name [1] 318744 0
Address [1] 318744 0
Country [1] 318744 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315354 0
Peter MacCallum Cancer Centre Human Research Ethics Committee
Ethics committee address [1] 315354 0
Ethics committee country [1] 315354 0
Australia
Date submitted for ethics approval [1] 315354 0
08/07/2024
Approval date [1] 315354 0
31/07/2024
Ethics approval number [1] 315354 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 134434 0
Dr Lara Edbrooke
Address 134434 0
The University of Melbourne, Level 7, 161 Barry St, Carlton, Victoria, 3053
Country 134434 0
Australia
Phone 134434 0
+61390354213
Fax 134434 0
Email 134434 0
larae@unimelb.edu.au
Contact person for public queries
Name 134435 0
Lara Edbrooke
Address 134435 0
The University of Melbourne, Level 7, 161 Barry St, Carlton, Victoria, 3053
Country 134435 0
Australia
Phone 134435 0
+61390354213
Fax 134435 0
Email 134435 0
larae@unimelb.edu.au
Contact person for scientific queries
Name 134436 0
Lara Edbrooke
Address 134436 0
The University of Melbourne, Level 7, 161 Barry St, Carlton, Victoria, 3053
Country 134436 0
Australia
Phone 134436 0
+61390354213
Fax 134436 0
Email 134436 0
larae@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data will be retained and may be shared for related research projects. De-identified data will be available to selected trial researchers.
When will data be available (start and end dates)?
Beginning 12 months following publication with no end date.
Available to whom?
Determined by the Chief Investigator on a case by case basis
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Proposals should be directed to the Chief Investigator – Dr Lara Edbrooke (larae@unimelb.edu.au) for approval


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.