Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000426189
Ethics application status
Approved
Date submitted
19/02/2019
Date registered
15/03/2019
Date last updated
7/07/2020
Date data sharing statement initially provided
15/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
ACE: Advanced Cancer & Cachexia Exercise Trial
Scientific title
Feasibility and efficacy of exercise in advanced cancer patients with cachexia
Secondary ID [1] 296777 0
Nil
Universal Trial Number (UTN)
Trial acronym
ACE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 310668 0
Cachexia 310669 0
Condition category
Condition code
Cancer 309371 309371 0 0
Any cancer
Musculoskeletal 310288 310288 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention will include supervised, small group-based (1-4 participants) aerobic and resistance exercise training three times per week over a 12 week period. Exercise sessions will be led by exercise physiologists who have experience working with individuals with cancer and will be delivered in community fitness centers. Continuous aerobic exercise will be performed on a stationary exercise bike or treadmill for 10-20 minutes at 55-65% estimated heart rate maximum (HRmax), or a Borg rating of perceived exertion (RPE) of 12-13 out of 20, for the first two weeks and will progress to moderate intensity interval training at 70-80% HRmax, or an RPE of 15-16. High intensity interval training sessions at 85-95% HRmax, or RPE of 18-19, will be introduced in week four. Resistance exercise will include up to six exercises to target major upper and lower body muscle groups (e.g. leg press, chest press, seated row) using machines, free weights or body weight. Resistance exercise will start at two sets at 10-12 repetition maximum (RM), progressing to 3-4 sets of 6-10 RM by week nine. Exercise will be modified and progressed according to individual tolerability. Compliance and attendance (including the reasons for missed sessions or inability to meet exercise targets) will be tracked throughout the intervention by the supervising exercise physiologist.

A 30 g serving of whey protein isolate powder (26 g of protein) mixed with 250-300 mL of water will be provided to all participants following each exercise session. Exercise physiologists will administer the protein supplement and track adherence.

Subgroup analyses will be performed on a select number of intervention and usual care participants who choose to opt-in to additional assessments upon enrollment in the trial.
Intervention code [1] 313082 0
Lifestyle
Comparator / control treatment
The usual care group will not be told to refrain from physical activity, however, they will have no exposure to a formalised exercise intervention during the main research study period. Following the study period, the usual care arm will be offered an identical 12 week supervised intervention (delayed exercise intervention).
Control group
Active

Outcomes
Primary outcome [1] 308330 0
Feasibility of participant recruitment (i.e. attrition) and retention, as measured as the proportion of patients screened and eligible versus those who consented and enrolled and the number of participants who do not request withdrawal from the study, respectively.
Timepoint [1] 308330 0
At the end of the 12 week intervention
Primary outcome [2] 308331 0
Feasibility of exercise session frequency (i.e. attendance), adherence to supervised aerobic and resistance exercise, tolerance of intervention and incidence/severity of any adverse events (e.g. muscle strain as a result of exercise) as measured by review of exercise session registers kept by the exercise physiologist.
Timepoint [2] 308331 0
At the end of the 12 week intervention
Primary outcome [3] 308332 0
Participant exercise program satisfaction measured using a researcher-generated questionnaire.
Timepoint [3] 308332 0
At the end of the 12 week intervention
Secondary outcome [1] 354623 0
Lean body mass and fat mass will be evaluated using dual-energy X-ray absorptiometry scans.
Timepoint [1] 354623 0
At baseline, 12 weeks and 24 weeks after randomisation
Secondary outcome [2] 368131 0
Muscular strength will be evaluated using tests for maximal leg press 1-repetition maximum, maximal hand grip strength and the 30 second chair rise.
Timepoint [2] 368131 0
At baseline, 12 weeks and 24 weeks after randomisation
Secondary outcome [3] 368132 0
Gait speed will be evaluated using the six minute walk test.
Timepoint [3] 368132 0
At baseline, 12 weeks and 24 weeks after randomisation
Secondary outcome [4] 368133 0
Maximal aerobic capacity will be estimated using a submaximal incremental aerobic exercise test on a cycle ergometer.
Timepoint [4] 368133 0
At baseline, 12 weeks and 24 weeks after randomisation
Secondary outcome [5] 368134 0
Physical activity and free-living energy expenditure will be evaluated using accelerometers.
Timepoint [5] 368134 0
At baseline, 12 weeks and 24 weeks after randomisation
Secondary outcome [6] 368135 0
Nutritional status will be evaluated using the Patient-Generated Subjective Global Assessment (PG-SGA).
Timepoint [6] 368135 0
At baseline, 12 weeks and 24 weeks after randomisation
Secondary outcome [7] 368136 0
Patient-reported cancer-specific quality of life and cachexia/anorexia symptoms will be evaluated using the Functional Assessment Anorexia/Cachexia Treatment (FAACT) questionnaire.
Timepoint [7] 368136 0
At baseline, 6 weeks, 12 weeks and 24 weeks after randomisation
Secondary outcome [8] 368137 0
General patient-reported quality of life will be evaluated using the Medical Outcomes Short Form (SF-36) questionnaire.
Timepoint [8] 368137 0
At baseline, 6 weeks, 12 weeks and 24 weeks after randomisation
Secondary outcome [9] 368138 0
Cancer-related fatigue will be evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F).
Timepoint [9] 368138 0
At baseline, 6 weeks, 12 weeks and 24 weeks after randomisation
Secondary outcome [10] 368139 0
Anxiety and depression will be evaluated using the Hospital Anxiety and Depression Scale (HADS).
Timepoint [10] 368139 0
At baseline, 6 weeks, 12 weeks and 24 weeks after randomisation
Secondary outcome [11] 368140 0
Self-reported physical activity levels will be evaluated using a modified Godin Leisure Time Exercise questionnaire.
Timepoint [11] 368140 0
At baseline, 6 weeks, 12 weeks and 24 weeks after randomisation
Secondary outcome [12] 368141 0
Dietary intake will be evaluated using a three-day food diary.
Timepoint [12] 368141 0
At baseline, 12 weeks and 24 weeks after randomisation
Secondary outcome [13] 368142 0
Exercise motivation and beliefs will be evaluated using a researcher-generated questionnaire based on the theory of planned behaviour.

Timepoint [13] 368142 0
At baseline, 6 weeks, 12 weeks and 24 weeks after randomisation
Secondary outcome [14] 368146 0
Resting metabolic rate will be evaluated via indirect calorimetry in a subgroup of participants who opt-in to complete these assessments upon enrollment.

Timepoint [14] 368146 0
At baseline, 12 weeks and 24 weeks after randomisation
Secondary outcome [15] 368231 0
One-on-one interviews (approx. 30 minutes) to explore key themes associated with the acceptability of exercise and the perceived impact of the intervention on well-being will be conducted by an experienced interviewer, not directly involved in delivering the intervention. All interviews will be audio recorded.
Timepoint [15] 368231 0
At the end of the 12 week intervention.

Eligibility
Key inclusion criteria
1. Confirmed diagnosis of advanced cancer (i.e. locally advanced or metastatic disease)
2. Body mass index (BMI) <30 mg/m2
3. Australian-modified Karnofsky Performance Status >70
4. Weight loss >5% within the past 6 months, or BMI <20 kg/m2 and weight loss >2% within the past 6 months, or presence of sarcopenia and weight loss >2% within the past 6 months
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Refractory cachexia
2. Expected survival <3 months
3. Receiving parenteral nutrition or enteral nutrition via feeding tube
4. Scheduled to undergo surgery within the study period
5. Neuroendocrine carcinoma (e.g. neuroendocrine pancreatic cancer)
6. Use of mobility aids including a brace, cane walker or wheelchair
7. Contraindication to exercise as determined by treating medical physician (e.g. uncontrolled medical condition)
8. Inability to read and communicate in English

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)
Group allocation (1::1) will be generated by a researcher independent to the current study and will be sealed in opaque envelopes. Written informed consent will be required prior to any testing or randomisation. Participants who dropout prior to completing baseline testing will not be randomised.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be performed using a computer generated random number generator. Randomisation is at the level of the individual patient and will be stratified by sex (male or female) and six minute walking distance (>400 m or <400 m).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The primary outcomes for this study are considered primarily descriptive and will be presented as means, medians, inter-quartile ranges or percentages, as appropriate. Linear mixed models followed by pairwise corrected contrasts will be used to evaluate the effect of time, group, and the group by time interaction for all secondary outcomes. All statistical models will be adjusted for potentially important covariates explaining residual outcome variance (e.g. age, BMI).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2019
Actual
1/07/2019
Date of last participant enrolment
Anticipated
1/07/2021
Actual
Date of last data collection
Anticipated
1/12/2021
Actual
Sample size
Target
56
Accrual to date
5
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 13186 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 13187 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 25741 0
3065 - Fitzroy
Recruitment postcode(s) [2] 25742 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 301352 0
University
Name [1] 301352 0
Mary MacKillop Institute for Health Research, Australian Catholic University
Country [1] 301352 0
Australia
Primary sponsor type
University
Name
Mary MacKillop Institute for Health Research, Australian Catholic University
Address
Level 5 - 215 Spring Street, Melbourne, VIC, 3000
Country
Australia
Secondary sponsor category [1] 301070 0
None
Name [1] 301070 0
Address [1] 301070 0
Country [1] 301070 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302096 0
St. Vincent's Hospital (Melbourne) Human Research Ethics Committee
Ethics committee address [1] 302096 0
41 Victoria Parade, Fitzroy, VIC 3065
Ethics committee country [1] 302096 0
Australia
Date submitted for ethics approval [1] 302096 0
12/12/2018
Approval date [1] 302096 0
11/02/2019
Ethics approval number [1] 302096 0
HREC 251/18

Summary
Brief summary
Cancer cachexia is a complex, multifaceted syndrome that remains both challenging to diagnose and treat. In addition to negatively impacting patients’ quality of life and decreasing physical function, cachexia may worsen cancer treatment side-effects and significantly impact patient prognosis. Exercise has been shown to be an effective strategy to manage the adverse effects of cancer and its treatment. However, whether these benefits extend to individuals with cancer cachexia has been underexplored. This project will therefore aim to evaluate whether an individualised, 12 week supervised exercise training program is safe, feasible and effective as a management strategy for cancer cachexia.

Who is this study for?
You may be eligible to join this study if you have a diagnosis of locally advanced or metastatic cancer and are experiencing involuntary weight loss.

Study details:
Participants will be randomly assigned (by chance) to one of two groups: 1) an immediate exercise group; or 2) a delayed exercise group. Both groups will continue to receive standard medical care. The immediate exercise group will commence a 12 week exercise program (36 sessions) plus protein supplementation (three days/week) immediately following enrollment. The delayed exercise group will receive usual care (i.e. no change to their current lifestyle) following enrollment and will be offered participation in an identical exercise intervention 12 weeks after randomisation.

In-person testing will be conducted at baseline, 12-weeks and 24 weeks. Testing will involve, strength and aerobic tests, a body scan, questionnaires and a fasted blood sample. Questionnaires will also be administered at 6-weeks but can be completed at home (online or paper copies). In addition, participants will be invited to complete optional assessments, which involve providing a muscle biopsy (sample of muscle tissue) and/or an evaluation of resting metabolic rate.

This research is a critical first step in to determine the most feasible and effective ways to utilise exercise as a strategy to counteract the burden of cachexia in individuals with advanced cancer and therefore lay the foundation for future research.
Trial website
https://mmihr.acu.edu.au/projects/ace-trial/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89094 0
A/Prof Prue Cormie
Address 89094 0
Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5 - 215 Spring Street, Melbourne, VIC, 3000
Country 89094 0
Australia
Phone 89094 0
+61 3 9230 8242
Fax 89094 0
Email 89094 0
[email protected]
Contact person for public queries
Name 89095 0
Ms Kelcey Bland
Address 89095 0
Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5 - 215 Spring Street, Melbourne, VIC, 3000
Country 89095 0
Australia
Phone 89095 0
+61 3 9830 8084
Fax 89095 0
Email 89095 0
[email protected]
Contact person for scientific queries
Name 89096 0
Ms Kelcey Bland
Address 89096 0
Mary MacKillop Institute for Health Research
Australian Catholic University
Level 5 - 215 Spring Street, Melbourne, VIC, 3000
Country 89096 0
Australia
Phone 89096 0
+61 3 9830 8084
Fax 89096 0
Email 89096 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Per ethics, we do not have permission to share IPD.


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.