Please note the ANZCTR will be unattended from Friday 20 December 2019 for the holidays. The Registry will re-open on Tuesday 07 January 2020. Submissions and updates will not be processed during that time.

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Trial registered on ANZCTR


Registration number
ACTRN12618000596202
Ethics application status
Approved
Date submitted
11/04/2018
Date registered
17/04/2018
Date last updated
15/10/2019
Date data sharing statement initially provided
15/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
An evidence-based intervention (“Fit for Treatment”) to prevent chemotherapy-induced neurotoxicity in breast cancer patients: An effectiveness-implementation hybrid study
Scientific title
An evidence-based intervention (“Fit for Treatment”) to prevent chemotherapy-induced neurotoxicity in breast cancer patients: An effectiveness-implementation hybrid study
Secondary ID [1] 294536 0
Nil known
Universal Trial Number (UTN)
U1111-1212-1253
Trial acronym
FFT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 307316 0
Chemotherapy-induced Peripheral Neuropathy 307329 0
Cardiovascular Disease Risk 307330 0
Condition category
Condition code
Cancer 306424 306424 0 0
Breast
Neurological 306438 306438 0 0
Other neurological disorders
Cardiovascular 306439 306439 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study involves two components. The first, an interventional study which will compare the effects of a 12-week exercise intervention to usual care in individuals with breast cancer undertaking eligible chemotherapy regimens. The second, a situational appraisal of this exercise intervention.

1. Exercise Intervention
The intervention will be a structured and individualised 12-week exercise program with the following components:
1) Participants will aim to complete 36 exercise sessions during this 12-week period (averaging 3 exercise sessions per week). If participants are unable to reach the target 36 sessions during these 12 weeks (i.e. they miss sessions due to excess treatment-related side effects), 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.
2) For twelve (or thirteen) weeks, an accredited exercise physiologist (AEP) will directly supervise three hour-long gym-based sessions per week at the School of Human Movement and Nutrition Sciences gymnasium, University of Queensland Healthy Living Clinic, or Princess Alexandra Hospital.
3) After six weeks, participants will then be given the option to be provided prescription for one of these three sessions as a self-managed home session, from weeks 7-12(13). 
4) The AEP will individually tailor exercises for patients whose arm movement is restricted as a result of prior breast surgery and individualised to enhance neuromuscular strength, endurance, balance, cardiorespiratory fitness and flexibility. The AEP will be cognisant of neutropenic risks (e.g. no swimming will be prescribed). 
5) High-intensity aerobic exercise will be prescribed during the intervention, individualised to the participants’ cardiorespiratory fitness and closely monitored by the AEP.
6) If participants decide to, and are deemed capable of, completing the second exercise session unsupervised at home from weeks 7-12(13) of the intervention, exercise maintenance strategies will be utilised to enhance adherence to the home-based exercise program.

2. Situational Appraisal
Princess Alexandra Hospital clinicians (chemotherapy nurses, physiotherapists, medical oncologists and service managers) and intervention participants will be invited to attend focus groups. Participants will be required to attend one of two focus groups, lasting no longer than 90 minutes in duration. Participants will be asked questions regarding resource utilisation, the knowledge and skills needed to implement the intervention, as well as cultural and structure barriers and facilitators.
Intervention code [1] 300834 0
Prevention
Intervention code [2] 300835 0
Treatment: Other
Intervention code [3] 300848 0
Lifestyle
Comparator / control treatment
Women with breast cancer undertaking eligible chemotherapy regimens randomised to the control group will continue with usual care, supplemented with advice about self-managed exercise and the lay version of the American Cancer Society exercise guidelines. Participants will be provided with a paper copy of these guidelines. Control group participants will be informed that they are not prohibited from exercising during the study period.
Control group
Active

Outcomes
Primary outcome [1] 305439 0
Change in cognitive function scores, as assessed via the Functional Assessment of Cancer Therapy - Cognitive (FACT-Cog) (Version 3) questionnaire
Timepoint [1] 305439 0
Baseline, 6 weeks, 12 weeks (Primary timepoint) and 36 weeks after randomisation
Primary outcome [2] 321686 0
Change in self-reported fatigue scores, as assessed via the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (Version 4) questionnaire
Timepoint [2] 321686 0
Baseline, 6 weeks, 12 weeks (Primary timepoint) and 36 weeks after randomisation
Secondary outcome [1] 345247 0
Changes in physical, social/family, emotional and functional well-being scores, as assessed via the Functional Assessment of Cancer Therapy - General (FACT-G) (Version 4) questionnaire
Timepoint [1] 345247 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [2] 345248 0
Changes in autonomic and sensorimotor peripheral neuropathy symptoms scores, as assessed via the Chemotherapy-induced Peripheral Neuropathy Assessment Tool (CIPNAT) questionnaire
Timepoint [2] 345248 0
Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, and 12 weeks and 36 weeks after randomisation
Secondary outcome [3] 345249 0
Change in quality of life scores, as assessed via the Assessment of Quality of Life – 8D (AQoL-8D) questionnaire
Timepoint [3] 345249 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [4] 345250 0
Changes in sensory function, as assessed via Mechanical Detection Thresholds using standardised von Frey monofilaments (1.65-6.65mN or 0.008-300g, respectively) bilaterally over the palmar surface of the middle finger and plantar surface of the middle toe
Timepoint [4] 345250 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [5] 345251 0
Changes in sensory function, as assessed via Vibration Disappearance Thresholds using a Rydel Seiffertuning Fork (64Hz, 8/8 scale) bilaterally over the palmar surface of the middle finger and plantar surface of the middle toe
Timepoint [5] 345251 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [6] 345252 0
Changes in location/s of sensory disturbance/s, as assessed via a body chart specially designed for this study
Timepoint [6] 345252 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [7] 345253 0
Changes in macro vascular function, as assessed via Brachial Artery Flow-mediated Dilation (BA-FMD) using doppler ultrasound
Timepoint [7] 345253 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [8] 345254 0
Changes in microvascular function, as assessed via Skin Blood Flow (SBF) using a PERIMED PeriFlux System 5000
Timepoint [8] 345254 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [9] 345255 0
Changes in macro vascular structure, as assessed via Carotid Intima-media Thickness (CIMT) using doppler ultrasound
Timepoint [9] 345255 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [10] 345256 0
Changes in macro vascular function, as assessed via Carotid Distensibility (CD) using both doppler ultrasound and a SphygmoCor XCEL PWA and PWV system
Timepoint [10] 345256 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [11] 345257 0
Changes in central blood pressures and pulse wave characteristics, as assessed via Pulse Wave Analysis (PWA) using a SphygmoCor XCEL PWA and PWV system
Timepoint [11] 345257 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [12] 345258 0
Changes in central pulse transfer times, as assessed via Pulse Wave Velocity (PWV) using a SphygmoCor XCEL PWA and PWV system
Timepoint [12] 345258 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [13] 345259 0
Changes in Autonomic Nervous System function, as assessed via Heart Rate Variability (HRV) using a resting 3-lead electrocardiogram
Timepoint [13] 345259 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [14] 345261 0
Changes in Autonomic Nervous System function, as assessed via heart rate and blood pressure responses to both deep breathing and a Valsalva Manoeuvre using a Finapres NOVA System
Timepoint [14] 345261 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [15] 345262 0
Changes in cytokine blood markers as assessed via;
- Interleukin 1 beta (IL-1beta)
- Interleukin 6 (IL-6)
- Interleukin 2 (IL-2)
- Tumor Necrosis Factor alpha (TNFalpha)
All bloods for Secondary Outcomes numbered 15-18 collected via 10mL and 5mL Ethylenediaminetetraacetic acid (EDTA) tubes, 10mL and 6mL serum tubes, and a 2mL glucose tube (33mL in total)
Timepoint [15] 345262 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [16] 345265 0
Changes in breast cancer cell growth, as assessed via cell culture analyses (using cell number assays and cell death assays)
All bloods for Secondary Outcomes numbered 15-18 collected via 10mL and 5mL Ethylenediaminetetraacetic acid (EDTA) tubes, 10mL and 6mL serum tubes, and a 2mL glucose tube (33mL in total)
Timepoint [16] 345265 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [17] 345266 0
Changes in metabolic and hormonal blood markers as assessed via;
- Low-density lipoprotein (LDL)
- High-density lipoprotein (HDL)
- Total cholesterol (TC)
- Triglycerides (TG)
- Fasting glucose
- Haemoglobin A1c (HbA1c)
- Insulin
- Insulin-like growth factor 1 (IGF-1)
- Arginine
- Citrulline
- Asymmetric dimethylarginine (ADMA)
- N-monomethylarginine (MMA)
- Global metabolite, proteome and subproteome analysis
All bloods for Secondary Outcomes numbered 15-18 collected via 10mL and 5mL Ethylenediaminetetraacetic acid (EDTA) tubes, 10mL and 6mL serum tubes, and a 2mL glucose tube (33mL in total)
Timepoint [17] 345266 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [18] 345267 0
Changes in inflammatory blood markers as assessed via;
- Cardiac Troponin-I
- Brain Natriuretic Peptide (BNP)
- High sensitivity C-reactive protein (CRP)
All bloods for Secondary Outcomes numbered 15-18 collected via 10mL and 5mL Ethylenediaminetetraacetic acid (EDTA) tubes, 10mL and 6mL serum tubes, and a 2mL glucose tube (33mL in total)
Timepoint [18] 345267 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [19] 345268 0
Changes in estimated overall muscle strength, as assessed via hand grip strength of both the dominant and non-dominant hands using a hand-held dynamometer
Timepoint [19] 345268 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [20] 345274 0
Changes in cardiorespiratory fitness (VO2Peak), as assessed via a Cardiopulmonary Exercise Test (CPET) using a cycle ergometer and metabolic system
Timepoint [20] 345274 0
Baseline, 12 weeks and 36 weeks after randomisation
Secondary outcome [21] 345604 0
Changes in habitual physical activity and sedentary behaviours, as assessed via accelerometery using a ActiGraph GT3X+ accelerometer
Timepoint [21] 345604 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation
Secondary outcome [22] 345606 0
Adverse Events (AE) occurrence during the intervention period, as assessed via weekly face-to-face contact (at exercise sessions) from baseline to week 12. AE which might be directly related to the intervention (to be determined by an Accredited Exercise Physiologist) will be assessed using the US Department of Health and Human Services Common Terminology Criteria for Adverse Events (CTCAE). Possible AE include: - Cardiac events (e.g. Myocardial Infarction, Stroke, Cardiac Arrhythmia) - Musculoskeletal events (e.g. Development of Lower Back Pain, Knee Pain) - Chemotherapy-related events (e.g. Fatigue development, Immunocompromised i.e. flu) - Concurrent breast cancer treatment-related events (e.g. Oedema development, Skin irritation
Timepoint [22] 345606 0
Every supervised exercise session from baseline to week 12(13), throughout the 12-week exercise intervention period (Intervention group ONLY)
Secondary outcome [23] 345608 0
Resource utilisation in both groups during the intervention period, as assessed via discussion in the situational appraisal component of the study. Discussion of labour (e.g. to deliver the intervention) and non-labour (e.g. gymnasium use, pain medication) costs. Resource use will be costed at market rates (e.g. industrial award rates for labour costs), for use in cost-effectiveness analyses.
Timepoint [23] 345608 0
Following exercise intervention completion
Secondary outcome [24] 351095 0
Evaluation of factors relating to participant adherence to the exercise intervention, as assessed via a Cancer Exercise Adherence Survey specially designed for this study
Timepoint [24] 351095 0
Baseline (Intervention group ONLY)
Secondary outcome [25] 351096 0
Changes in habitual physical activity, as assessed via the Godin Leisure-Time Exercise Questionnaire (Godin) questionnaire
Timepoint [25] 351096 0
Baseline, 6 weeks, 12 weeks and 36 weeks after randomisation

Eligibility
Key inclusion criteria
- >18 years of age
- Chemotherapy-naive breast cancer patients prescribed any chemotherapy regimen (excluding regimens containing denosumab, everolimus, or zoledronic acid)
- >1 month post-surgery
- No concurrent cancer treatment while enrolled (individuals using Tamoxifen or Herceptin, or undergoing radiotherapies, will be eligible)
- No co-morbid condition or falls risk that could prevent safe completion of intervention
- Cognitively capable of consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Individuals who have undertaken prior chemotherapy treatment for any cancer
- Not planning to undergo surgery during the intervention period
- Any intellectual or physical disability which would make exercise intervention participation unsafe for the individual

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is concealed at baseline. The randomisation process for this trial is performed by a person external to the study (an academic from The University of Queensland, St Lucia). A Chief Investigator for the trial then contacts the external person, who informs them of the participant’s randomisation at the conclusion of baseline testing sessions.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Individuals who consent to participate in the trial are randomised at a 1:1 ratio to either the intervention or control group by the external person. Randomisation is performed electronically online using permuted block randomisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
102 participants are required for >90% power to detect a clinically important mean difference of 14.8 points between groups at any assessment on the primary outcome (FACT-Cog). This assumes up to 21% attrition, SD=20.4 and alpha=0.05.

Statistical analyses of raw data will be conducted on IBM SPPS Statistics for iOS. Categorical outcomes will be described using frequencies and proportions, and analysed using general estimating equations with a logistic regression model to account for repeated measures. ORs and 95% CIs will be reported. Control and intervention groups will be compared for continuous outcomes using mean/SD or median/interquartile range if not normally distributed. To account for the repeated measures, continuous outcome measures will be modelled using linear mixed-models. Assumptions of models will be examined by plotting the residuals using histograms and skewness and kurtosis measures. If the data do not meet assumptions, the 95% CIs will be bootstrapped to provide reliable estimates. Models will only be adjusted for characteristics that were unbalanced between groups and related to the outcome variable.

Recruitment
Recruitment status
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)
QLD
Recruitment hospital [1] 10610 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 22327 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 299163 0
Government body
Name [1] 299163 0
Queensland Government Department of Health, Nursing and Midwifery Research Fellowship
Address [1] 299163 0
Health and Medical Research Unit, Queensland Health, GPO Box 48, Brisbane, QLD, 4001
Country [1] 299163 0
Australia
Funding source category [2] 299177 0
University
Name [2] 299177 0
School of Human Movement and Nutrition Sciences - University of Queensland
Address [2] 299177 0
School of Human Movement and Nutrition Sciences (#26B), Cnr Blair Drive & Union Road, The University of Queensland, St Lucia Campus, Queensland, 4072
Country [2] 299177 0
Australia
Primary sponsor type
Individual
Name
Tina Skinner
Address
Senior Lecturer in Exercise Physiology

School of Human Movement and Nutrition Sciences (#26B), Cnr Blair Drive & Union Road, The University of Queensland, St Lucia Campus, Queensland, 4072
Country
Australia
Secondary sponsor category [1] 298419 0
Individual
Name [1] 298419 0
Alexandra McCarthy
Address [1] 298419 0
Head of School

The School of Nursing, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland, 1142
Country [1] 298419 0
New Zealand
Secondary sponsor category [2] 298433 0
Individual
Name [2] 298433 0
Leanne Stone
Address [2] 298433 0
Director of Nursing

Division of Cancer Services, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, Queensland, 4102
Country [2] 298433 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300087 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 300087 0
PAH Centres for Health Research, Level 7, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland, 4102
Ethics committee country [1] 300087 0
Australia
Date submitted for ethics approval [1] 300087 0
17/01/2018
Approval date [1] 300087 0
05/04/2018
Ethics approval number [1] 300087 0
HREC/18/QPAH/38

Summary
Brief summary
The purpose of this research study is to implement and evaluate a neurotoxicity-targeted intervention during chemotherapy for breast cancer.

Who is it for?
You may be eligible to join this study if you aged 18 years or more and are a chemotherapy-naive breast cancer patient prescribed a chemotherapy regimen.

Study details
Participants in this study will be randomly allocated (by chance) to either 12-weeks of an exercise intervention or usual care. Participants in the exercise intervention group complete cardiorespiratory/aerobic, resistance, balance and stretching exercises on 3 days of the week; which are individually tailored to each intervention participant. Participants in both groups are required to undertake assessments both before, during and after the 12-week intervention period. These assessments are related to neurotoxicity development, cardiovascular disease risk development and other health measures (e.g. body composition, blood markers, overall body strength, cardiorespiratory fitness).

Some participants will also be invited to attend a focus group discussion on the quality and feasibility of the intervention after intervention completion.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 3039 3039 0 0
Attachments [2] 3040 3040 0 0

Contacts
Principal investigator
Name 82526 0
Dr Tina Skinner
Address 82526 0
Senior Lecturer in Exercise Physiology

School of Human Movement and Nutrition Sciences (#26B), Cnr Blair Drive & Union Road, The University of Queensland, St Lucia Campus, Queensland, 4072
Country 82526 0
Australia
Phone 82526 0
+61 7 3346 8810
Fax 82526 0
Email 82526 0
t.skinner@uq.edu.au
Contact person for public queries
Name 82527 0
Miss Natalie Vear
Address 82527 0
PhD Student

School of Human Movement and Nutrition Sciences (#26B), Cnr Blair Drive & Union Road, The University of Queensland, St Lucia Campus, Queensland, 4072
Country 82527 0
Australia
Phone 82527 0
+61 4 7355 0978
Fax 82527 0
Email 82527 0
n.vear@uq.edu.au
Contact person for scientific queries
Name 82528 0
Dr Tina Skinner
Address 82528 0
Senior Lecturer in Exercise Physiology

School of Human Movement and Nutrition Sciences (#26B), Cnr Blair Drive & Union Road, The University of Queensland, St Lucia Campus, Queensland, 4072
Country 82528 0
Australia
Phone 82528 0
+61 7 3346 8810
Fax 82528 0
Email 82528 0
t.skinner@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We anticipate that the individual participants' data will not be made available on a publicly available repository. Should a journal request that the data be made available, we will apply for an amendment to make individual participant data available.
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 1459 0
Ethical approval
Citation [1] 1459 0
Link [1] 1459 0
Email [1] 1459 0
Other [1] 1459 0
Ethical approval letter from Metro South Human Research Ethics Committee for Initial Application
Type [2] 1460 0
Ethical approval
Citation [2] 1460 0
Link [2] 1460 0
Email [2] 1460 0
Other [2] 1460 0
Ethical approval letter from Metro South Human Research Ethics Committee for Amendment #1
Type [3] 1461 0
Ethical approval
Citation [3] 1461 0
Link [3] 1461 0
Email [3] 1461 0
Other [3] 1461 0
Ethical approval letter from Metro South Human Research Ethics Committee for Amendment #2
Type [4] 1462 0
Ethical approval
Citation [4] 1462 0
Link [4] 1462 0
Email [4] 1462 0
Other [4] 1462 0
Ethical approval letter from Metro South Human Research Ethics Committee for Amendment #3
Summary results
No Results