Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000050853
Ethics application status
Approved
Date submitted
18/08/2020
Date registered
19/01/2021
Date last updated
9/02/2024
Date data sharing statement initially provided
19/01/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Enhancing treatment outcomes after gynaecological cancer (ACUMEN): Using exercise to promote health after cancer therapy
Scientific title
Enhancing treatment outcomes after gynaecological cancer (ACUMEN): Investigating the effect of exercise on health-related quality of life after cancer therapy
Secondary ID [1] 301793 0
Medical Research Future Fund APP1199890
Secondary ID [2] 301794 0
Sponsor ref number (University of Queensland) 2020000196
Universal Trial Number (UTN)
U1111-1255-3934
Trial acronym
ACUMEN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gynaecological cancer 318269 0
Condition category
Condition code
Cancer 316281 316281 0 0
Ovarian and primary peritoneal
Cancer 316282 316282 0 0
Cervical (cervix)
Cancer 316285 316285 0 0
Womb (Uterine or endometrial cancer)
Cancer 316286 316286 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The total study period is 24 weeks. It comprises of a 12-week exercise training intervention and a 12-week maintenance period. After participant screening and baseline assessment, participants will be randomised to either the intervention or control group.

Participants allocated to the control group will receive standard care and will receive general advice about self-managed exercise, a Fitbit, and the Exercise is Medicine guidelines for gynaecological cancer. Control participants will be asked to wear the Fitbit device to assess physical activity performed over the study period.

Participants assigned to the intervention group will received one-on-one supervision by an Accredited Exercise Physiologists or Physiotherapists (AEPP). Goals will be prioritised and set with the participant and the prescription co-designed with the participant, including strategies for relapse prevention and longer-term maintenance. As part of this process, the 12-week exercise training intervention will adhere to the following principles:
1. Participants will be screened for known disease and risk of adverse events due to exercise with the Adult Pre-Exercise Screening System (APSS).
2. The goal is to enhance neuromuscular strength, endurance, balance, flexibility, cardiorespiratory fitness and cardiovascular function. The AEPP will individually tailor exercise to the functional capacity of each participant towards these goals, cognisant of potential restrictions caused by surgical scarring, pain, metastases, lymphoedema, obesity, incontinence or neuropathic problems.
3. Participants will aim for 3 x 60 minute exercise sessions per week, individually prescribed by an Accredited Exercise Physiologist or Physiotherapist (AEPP) based on APSS results and the participant’s limitations, preferences and goals. The session will aim for an aerobic component (up to 40 minutes of moderate-to-high intensity) and resistance component (2 x 6-8 repetitions of major muscle group exercises at >8-10 on the OMNI perceived exertion scale, where 0=extremely easy to 10=extremely hard). Adjustments to exercise dose are dependent upon target cancer outcome/s (including cancer-related fatigue, health-related quality of life, physical function, lymphedema, bone health, and sleep).
4. Supervised aerobic exercise will include but are not limited to a bike ergometer, treadmill, rowing, and cross-trainer. Unsupervised homebased aerobic exercise will be prescribed based on the accessibility of the participant. Walking, stepping, water exercise and cycling are examples of home-based aerobic activity. Dynamic resistance exercises, using both concentric and eccentric muscle contractions of major muscle groups will include, but are not limited to, free-weights, resistance bands, resistance machines, and weight-bearing functional tasks. Priority and focus of exercise will be informed by participant driven goals of exercise and exercise considerations.
5. High-intensity interval aerobic exercise may be prescribed during the intervention, individualised to the participants’ cardiorespiratory fitness and peak heart rate, and closely monitored by the AEPP.
6. The aerobic exercise intensity will be prescribed based on individual peak heart rate obtained from the cardiorespiratory fitness test. Exercising heart rate will be monitored by the FitBit watch during all exercise training sessions (supervised and home-based). Target heart rate will be prescribed at 40-70% of peak heart rate for moderate intensity exercise and 85-95% of peak heart rate for high-intensity interval exercise. Rating of perceived exertion (RPE) using the Borg scale will also be used to facilitate the prescription of exercise intensity.
7. Participants will aim to complete 36 exercise sessions during the 12-week period (3 exercise sessions per week). If participants are unable to reach the target 36 sessions during the 12 weeks (i.e. they miss sessions due to illness or other commitments), then they will be provided with the option of performing make-up sessions during this 12-week period (i.e. a participant may complete 2 sessions one week, then 4 sessions the following week). Alternatively, participants will be provided with the option of completing as many of the remaining sessions as possible during one additional week, making the intervention 13 weeks in duration (at most) for these participants). Regardless of the number of sessions missed, a maximum of 4 sessions will be performed in the additional week. The sessions will mimic the type of session they have missed i.e. supervised or home-based.
8. For the first six weeks, each participant will receive two supervised gym-based sessions per week at a fully-equipped gymnasium, and one self-managed home-based session per week.
9. In Weeks 7-12, participants will be asked to attend one supervised session per week, and increase their home-based exercise prescription to two times per week for six more weeks.
10. Intervention group attendance and adherence at supervised sessions will be recorded by the intervention AEPP, with unsupervised sessions recorded by the participant and reported weekly to the AEPP. Intervention participants will be asked to wear the FitBit during each exercise session (including at home) to closely monitor adherence to prescribed exercise intensity (heart rate).
11. All exercise sessions will be prescribed, logged and tracked using PhysiTrack©.
12. Intervention and control participants will be asked tocontinuously wear a Fitbit throughout the study. Physical activity will be assessed over seven consecutive days prior to study commencement, and for 7 days each throughout Weeks 12 and 24 to accurately track and compare the intensity of daily physical activities. Unsupervised exercise sessions will also be tracked and logged by the Fitbit
13. The secondary outcome of the project is to assess participants’ confidence in their ability to perform exercise without AEPP supervision between week 13 and week 24 (long-term maintenance). In the 12 week maintenance period, intervention participants will be asked to continue with their home-based exercise sessions. However, no support or feedback will be provided by the AEPP or research team. All participants will be asked to continue to wear the FitBit device during the 12-week maintenance period so exercise can be monitored.

Duration and intensity of daily physical activities will be tracked during the monitoring period. Intervention participants will be required to wear a FitBit throughout Weeks 13-24 to accurately track the intensity of daily physical activities, including the unsupervised exercise sessions.
Intervention code [1] 318288 0
Treatment: Other
Intervention code [2] 318289 0
Rehabilitation
Intervention code [3] 318290 0
Lifestyle
Comparator / control treatment
Participants allocated to the control group will receive standard care as usual, which may include scheduled clinical visits as normal. This will be supplemented with general advice about self-managed exercise, a Fitbit to monitor physical activity, and the Exercise is Medicine guideline for gynaecological cancer. The control group will undergo all assessment outcomes at baseline, week 12 and week 24. This includes a 7-day physical activity assessment at each time-point by wearing the Fitbit watch. Participants will also be encouraged at the start of the study to wear the Fitbit device throughout the 24 week period so they can self-manage levels of physical activity.
Control group
Active

Outcomes
Primary outcome [1] 324709 0
The mean difference on the physical component summary (PCS) scores of health-related quality of life between intervention and control in this trial, as measured by the Short Form-36 (SF36).
Timepoint [1] 324709 0
Baseline (pre-intervention), week 12 (primary time-point, end of intervention) and week 24 (longer-term maintenance)
Primary outcome [2] 325741 0

The mean difference on the mental component summary (MCS) scores of health-related quality of life between intervention and control in this trial, as measured by the SF36.
Timepoint [2] 325741 0

Baseline (pre-intervention), week 12 (primary time-point, end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [1] 385471 0
Exercise self-efficacy as measured by the Exercise Self-efficacy Scale (ESES).
Timepoint [1] 385471 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [2] 385472 0
Cardiorespiratory fitness (VO2peak and exercise capacity) assessed during a graded cycling test with breath-by-breath gas analysis
Timepoint [2] 385472 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [3] 388952 0
Balance (assessed via centre of pressure displacement techniques)
Timepoint [3] 388952 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [4] 388953 0
Dynamic upper and lower body muscle strength (chest and leg press respectively using one repetition maximum).
Timepoint [4] 388953 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [5] 388954 0
Body composition measured via waist-hip ratio with a measuring tape according to WHO STEPwise Approach to Surveillance (STEPS) protocol for consistent measurement. .
Timepoint [5] 388954 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [6] 388956 0
Blood markers of inflammatory modulation (assessed by the levels of TNF-a, IL-2, IL1ß, IL-6 and IL-8 in blood).
Timepoint [6] 388956 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [7] 388957 0
Blood markers of glycaemic modulation (assessed by HBA1c levels in blood).
Timepoint [7] 388957 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [8] 389918 0
Blood markers for steroid hormone modulation - follicle stimulating hormone
Timepoint [8] 389918 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [9] 390674 0
Blood markers for steroid hormone modulation - oestradiol
Timepoint [9] 390674 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [10] 390675 0
Blood markers for steroid hormone modulation - progesterone
Timepoint [10] 390675 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [11] 390676 0
Blood markers for steroid hormone modulation - luteinizing hormone
Timepoint [11] 390676 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [12] 390677 0
Frequency of physical activity levels as assessed by the Fitbit watch.
Timepoint [12] 390677 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [13] 390678 0
Intensity of physical activity levels as assessed by the Fitbit watch.
Timepoint [13] 390678 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [14] 390679 0
Duration of physical activity levels as assessed by the Fitbit watch.
Timepoint [14] 390679 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [15] 431536 0
Genetic marker extracted from the blood sample to monitor response to fitness intervention.
Timepoint [15] 431536 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [16] 431537 0
Subjective lower-limb lymphoedema-related symptoms as assessed by the Gynaecological Cancer Lymphoedema Questionnaire (GCLQ).
Timepoint [16] 431537 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [17] 431538 0
Subjective lower-limb lymphoedema-related symptoms as assessed by the Gynaecological Cancer Lymphoedema Questionnaire (GCLQ).
Timepoint [17] 431538 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [18] 431539 0
Objective symptoms of lower-limb lymphoedema using bioelectrical impedance.
Timepoint [18] 431539 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).
Secondary outcome [19] 431540 0
Objective symptoms of lower-limb lymphoedema using bioelectrical impedance.
Timepoint [19] 431540 0
Baseline (pre-intervention), week 12 (end of intervention) and week 24 (longer-term maintenance).

Eligibility
Key inclusion criteria
1. Women > 18 years diagnosed with cancer of the ovary, cervix, Fallopian tubes, placenta, endometrium, vagina or vulva in the previous 60 months, including early, recurrent, advanced or metastatic cancer.
2. > 1 month since end of intensive cancer treatment (including surgery, radiotherapy, chemotherapy). Supportive therapies such as bisphosphonate, pain medication and hormone replacement allowable.
3. Resident in Australia.
4. Have access to the internet.
5. Own, or have access to, a computer, smart phone or tablet device.
6. Willing and able to comply with all study requirements, including intervention, timing and nature of required assessments.
7. Able to speak and read in English to ensure consent is informed and documentation of participant-reported outcome measures can be adhered to.
8. Can provide voluntary written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any clinical contraindication that precludes safe completion of the program in the judgement of the project team.
2. No intensive cancer treatments while enrolled.
3. In the care of an exercise professional at the time of enrolment.

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)
Allocation involves contacting the holder of the allocation schedule who is "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Differences in diagnosis and treatment characteristics between gynaecological cancer stages may influence patient reported outcomes, including quality of life and physical activity levels. A poorer health-related quality of life has been found in patients with a higher tumour stage, and women with advanced disease report smaller positive changes in health-related quality of life following treatment for gynaecological cancer. For this reason, we will stratify by cancer stage in this study. Patients in each stratum was determined by using probability proportion to size approach, based on the number of gynaecological cancer cases registered at QCGC [Queensland Centre for Gynaecological cancer] by stages over the past five years 2013-2017. Patients in each stratum will then be randomly allocated into one of the two groups using a block randomisation.
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
A sample of 166 per group is needed to achieve 80% power in order to detect a mean difference of 4.4 on the PCS and MCS between intervention and control in this superiority trial. This assumes a standard deviation of 8.6 and a superiority margin of 2.1, using a one-sided t-test with a significance level of 0.025. The mean difference and standard deviation are derived from our previous trial with 351 women of a lifestyle intervention after early stage cancer treatment (APP1056856). Considering an attrition rate of ~15% reported in exercise intervention trials in cancer populations, the trial needs a total of 171 per group, which gives a total sample size of 342. The proportions of participants approached and recruited, and the proportion retained at 12 weeks and 24 weeks will be reported with 95% CIs.

Results from the randomised controlled trials
Data will be analysed on an intention-to-treat basis. Before modelling trial outcomes, the characteristics of the two groups will be examined to establish the extent to which randomisation succeeded in creating comparable groups. In the event that any characteristics are not comparable at baseline, they will be modelled as covariates in subsequent analyses to adjust for their possible confounding effects. Collinearity of the covariates will be assessed before including them in the modelling. Missing values, which are inevitable in any trial, will be examined for their patterns and distributions, and multiple imputation will be used if all relevant assumptions are met. Linear mixed-models will evaluate the effectiveness of the intervention at 12 and 24 weeks on the primary outcomes (PCS and MCS). Linear mixed-models will examine change over time in intervention and control groups for all variables of interest. Interaction between group and time will be examined to test whether the groups act differently at different timepoints. All relevant assumptions of the modelling exercise, including the examination of residuals, will be assessed in order to make valid inferences about the treatment effects. A sensitivity analysis to account for missing data and their potential effect on the observed results will be performed. Analyses to address the secondary objectives will follow the same approach.

Implementation Appraisal
The Acceptability, Appropriateness and Feasibility of Intervention Measures (AAFIM) data are ordinal, hence descriptive statistics e.g., median and percentiles, number of cases, modes, and contingency correlations will be determined. For cost-effectiveness assessment, economic decision modelling will be used to estimate the long-term costs and effects of the intervention compared with the standard of care. Model input parameters will include costs, utility scores, and transition probabilities between health states. These parameters will be obtained from Study 1 and from a systematic review and synthesis of relevant published evidence. Sensitivity and scenario analyses will be conducted to test the robustness of the results. Qualitative data will be transcribed, coded according to the five Consolidated Framework for Implementation Research (CFIR) factors and thematically analysed. Statistical data will be triangulated with the qualitative data to report comprehensively on intervention acceptability, appropriateness and feasibility.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2021
Actual
29/04/2021
Date of last participant enrolment
Anticipated
30/04/2025
Actual
Date of last data collection
Anticipated
31/05/2025
Actual
Sample size
Target
342
Accrual to date
148
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 17231 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 17232 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [3] 17233 0
Mater Women's & Children's Private Health Services - South Brisbane
Recruitment hospital [4] 17234 0
Genesis Cancer Care - Wesley - Auchenflower
Recruitment hospital [5] 17235 0
Icon Cancer Care Wesley - Auchenflower
Recruitment hospital [6] 17236 0
The Wesley Hospital - Auchenflower
Recruitment hospital [7] 17237 0
Greenslopes Private Hospital - Greenslopes
Recruitment postcode(s) [1] 30943 0
4029 - Herston
Recruitment postcode(s) [2] 30944 0
4101 - South Brisbane
Recruitment postcode(s) [3] 30945 0
4066 - Auchenflower
Recruitment postcode(s) [4] 30946 0
4120 - Greenslopes
Recruitment postcode(s) [5] 42025 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 306227 0
Government body
Name [1] 306227 0
Medical Research Future Fund
Country [1] 306227 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
The University of Queensland
St Lucia
Brisbane
QLD 4072
Country
Australia
Secondary sponsor category [1] 306942 0
None
Name [1] 306942 0
Address [1] 306942 0
Country [1] 306942 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306438 0
Royal Brisbane and Women’s Hospital ethics committee
Ethics committee address [1] 306438 0
Level 14 Block 7
Royal Brisbane and Women's Hospital
Cnr Butterfield St and Bowen Bridge Rd
HERSTON QLD 4029
Ethics committee country [1] 306438 0
Australia
Date submitted for ethics approval [1] 306438 0
22/09/2020
Approval date [1] 306438 0
09/11/2020
Ethics approval number [1] 306438 0
HREC/2020/QRBW/67832

Summary
Brief summary
The ACUMEN trial will examine the effect of an exercise program on the physical and mental health-related quality of life in women treated for reproductive cancer, with the aim to promote regular exercise for these patients.

Who is it for?
If you are an adult woman who has been diagnosed with gynaecological in the 60 months, and it has been over a month since you finished an intensive cancer treatment (including surgery, radiotherapy, chemotherapy), you may be eligible to participate in this study.

Study details
Participants in this study will be randomly assigned to one of two groups. The first group will undergo an individual assessment with a trained accredited exercise physiologist or physiotherapist to determine their current fitness levels. Participants in this first group will then be prescribed a personalised exercise program that they will follow for the next 12 weeks. The exercise program will include both aerobic and resistance training and participants will be asked to complete 3x 60 minute sessions each week for the 12 week period which will include supervised and unsupervised sessions. The second group of participants will not be prescribed an exercise program and will continue to see their usual health professionals as required. Participants in the second group will be given written information regarding exercise as part of a healthy lifestyle and for cancer recovery, and a Fitbit activity tracker to monitor their physical activity over the 12 week period.

Participants in both groups will complete a series of questionnaires, a blood sample and fitness assessments before and after the intervention. After the intervention, questionnaires, blood samples and fitness assessments will occur at two time-points (week 12 and week 24).

It is hoped this research will determine whether a personalised exercise program can lead to improved long-term health outcomes for women who have been treated for gynaecological cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103874 0
Prof Alexandra McCarthy
Address 103874 0
School of Nursing Midwifery and Social Work
The University of Queensland
St Lucia, QLD 4072
Country 103874 0
Australia
Phone 103874 0
+61 0428566283
Fax 103874 0
Email 103874 0
[email protected]
Contact person for public queries
Name 103875 0
Prof Alexandra McCarthy
Address 103875 0
School of Nursing Midwifery and Social Work
The Whitty Building
Mater Research Institute
The University of Queensland
Brisbane, QLD 4101
Country 103875 0
Australia
Phone 103875 0
+61 0428566283
Fax 103875 0
Email 103875 0
[email protected]
Contact person for scientific queries
Name 103876 0
Prof Alexandra McCarthy
Address 103876 0
School of Nursing Midwifery and Social Work
The Whitty Building
Mater Research Institute
The University of Queensland
Brisbane, QLD 4101
Country 103876 0
Australia
Phone 103876 0
+61 0428566283
Fax 103876 0
Email 103876 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
Aggregate data will be available on application to other researchers.


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.