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Trial registered on ANZCTR


Registration number
ACTRN12618000225213
Ethics application status
Approved
Date submitted
31/01/2018
Date registered
12/02/2018
Date last updated
14/01/2021
Date data sharing statement initially provided
30/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Exercise for men with prostate cancer on active surveillance
Scientific title
Can exercise delay transition to active therapy in men with low grade prostate cancer? A multi-centre randomized controlled trial
Secondary ID [1] 293928 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 306417 0
Condition category
Condition code
Cancer 305505 305505 0 0
Prostate
Physical Medicine / Rehabilitation 305587 305587 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single-blinded (investigators blinded to group allocation), two arm, multi-centre RCT that will examine the efficacy of combined resistance and aerobic exercise during AS on disease progression in men with low-risk PCa. An ‘Exercise’ group will complete a 6-month supervised exercise intervention followed by a stepped down program for 6 months and a subsequent self-managed maintenance program for 2 years.

One hundred and sixty-eight men (84 subjects per arm) within 1 year of prostate biopsy and undergoing AS will be recruited by invitation of their attending specialist from two Australian cities (Perth and Melbourne). Patients suitable for AS will be selected from the Multi-Disciplinary Uro-Oncology meeting at the recruiting site. Inclusion criteria are: 1) histologically proven adenocarcinoma of the prostate, 2) no prior therapy for PCa, 3) fit for curative intent therapy, 4) willing to attend follow-up, 5) clinical stage less than or equal to T2, 6) less than or equal to 10 % Gleason pattern 4 disease on biopsy with no more than 2 cores positive for cancer, and 7) PSA less than or equal to 10ng/ml. Exclusion criteria are: 1) already performing regular exercise defined as undertaking structured resistance and aerobic training two or more times per week within the past 3 months, 2) acute illness or any musculoskeletal, cardiovascular or neurological disorder that could inhibit exercise performance or put participants at risk from exercising, 3) variant histopathology (small cell, intra-ductal, sarcomatoid), presence of extra-prostatic extension (EPE) or lympho-vascular invasion (LVI), 4) patient no longer considered a candidate for curative intent treatment, and 5) intention to move place of residence away from the two study sites. Eligible subjects will undertake baseline measurements prior to randomisation.

The exercise intervention will consist of supervised resistance and aerobic exercise performed over 3 sessions per week for 6 months in an exercise clinic setting. During months 7-12, the exercise intervention group will transition to once a week supervised exercise in a clinic for months 7-8, once every two weeks supervised exercise in months 9-10, and once per month supervised exercise in months 11-12. This stepped down approach will include a self-managed exercise program consisting of a booklet (designed specifically for this study) and training log with detailed information about the exercise prescription and how to implement in a variety of settings. Participants will be encouraged and supported to continue their aerobic and resistance exercise program in their local fitness centre or other exercise facilities where they can maintain a high-quality exercise program under their self-management. The self-managed exercise program is designed to replicate the exercises performed in the supervised sessions and includes resistance, aerobic and flexibility exercises. Finally, from month 13 to 36 the exercise program will exclusively consist of a self-managed program and has been implemented by our group previously in a multicentre year-long trial in men with PCa on active therapy. The initial program will be supervised by exercise physiologists in Perth and Melbourne. Patient attendance/adherence will be recorded using training diaries.
The exercise program is designed to provide optimal stimulus to the cardiorespiratory and neuromuscular systems while maximising safety, compliance and retention. The exercise sessions will be conducted in small groups of up to 10-12 participants exercising in pairs under direct supervision to ensure correct technique and minimise the risk for injury. Resistance exercise will involve 6-8 exercises that target the major upper and lower body muscle groups. Intensity will be manipulated from 6-12 repetition maximum (RM; i.e. the maximal weight that can be lifted 6 to 12 times which is equivalent to ~60-85% of 1RM) using 1-4 sets per exercise. The aerobic exercise component will include 20 to 30 minutes of moderate to vigorous intensity cardiovascular exercise (~60-85% of estimated maximum heart rate) using a variety of modes such as walking or jogging on a treadmill, cycling or rowing on a stationary ergometer. Participants will be encouraged to undertake additional aerobic exercise outside the clinic sessions with the goal of achieving a total of at least 150 minutes of moderate to vigorous intensity aerobic exercise each week. Exercise prescription will be progressive and modified according to individual response. Both moderate intensity continuous and high intensity interval training will be implemented to provide greater variety and training stimulus. To reduce the possibility of boredom and over-reaching, the exercise program will be periodised by cycling emphasis on intensity and volume. We have used this exercise prescription effectively in previous trials involving men with PCa and have reported significant improvements in quality of life, lean muscle mass, fatigue, aerobic capacity and physical function. The step-down approach to self-management is intended to maximise the translation of this intervention to best practice management of this patient population.
Intervention code [1] 300197 0
Treatment: Other
Comparator / control treatment
The usual care group will receive an unsupervised walking program and an educational booklet (designed specifically for this study), outlining the current national physical activity recommendation for cancer survivors along with a logbook to record their physical activity. During the study, both groups will be encouraged to maintain customary dietary patterns and the Mini Nutritional Assessment will be used to monitor nutritional status.
Control group
Active

Outcomes
Primary outcome [1] 304638 0
Transition to active therapy measured by the number of patients undergoing active therapy (radical prostatectomy, radiotherapy, or androgen deprivation), and the time they began active therapy Data will be extracted directly from Urologist Clinical Investigators as part of their routine clinical practice, therefore all patients will be captured.
Timepoint [1] 304638 0
Baseline, 6 months, 12 months (primary endpoint), 24 months, 36 months
Secondary outcome [1] 342637 0
Disease Progression (PSA levels greater than or equal to 10 microgram/L) will be determined by a blood sample. A 30ml venous blood sample will be collected by an Australian National Association of Testing Authorities accredited laboratory.
Timepoint [1] 342637 0
Baseline, 6 months, 12 months, 24 months, 36 months
Secondary outcome [2] 342638 0
Change in body composition will be derived from whole body dual-energy X-ray absorptiometry scans. Trunk adiposity, visceral fat and adipose indices will be assessed using standard procedures.
Timepoint [2] 342638 0
Baseline, 6 months, 12 months, 24 months, 36 months
Secondary outcome [3] 342639 0
Quality of life will be measured using the Medical Outcomes Short Form 36 (SF-36v2) Questionnaire.
Timepoint [3] 342639 0
Baseline, 6 months, 12 months, 24 months, 36 months
Secondary outcome [4] 342640 0
Costs and economic analysis. Hospital resource use and associated costs will be obtained to assess costs for secondary healthcare for the exercise and usual care groups. All hospital events, including Emergency Department attendances, outpatient visits and procedures, and inpatient admission for all causes will be sought. In addition, the costs for providing the exercise intervention will be identified through the study. An alongside trial economic evaluation will be undertaken to assess the health benefits and additional costs compared to usual care.
Timepoint [4] 342640 0
Baseline, 6 months, 12 months, 24 months, 36 months
Secondary outcome [5] 342641 0
Effect mediators - The Masculinity in Chronic Disease Scale will assess the extent to which men identify with six masculine values: Strength; Sexual Importance/Priority; Family Responsibilities; Emotional Self-Reliance; Optimistic Capacity; and Action Approach.
Timepoint [5] 342641 0
Baseline, 6 months, 12 months, 24 months, 36 months
Secondary outcome [6] 342642 0
Physical function - A battery of standard tests will be used to assess physical function: 1) 400-m walk (aerobic capacity), 2) one repetition maximum for the leg press and chest press (muscular strength), and 3) repeated chair rise (lower body muscle function).
Timepoint [6] 342642 0
Baseline, 6 months, 12 months, 24 months, 36 months
Secondary outcome [7] 342896 0
Change in muscle density (an indicator of fat infiltration within the muscle) and muscle cross-sectional areas of the upper and lower limbs will be measured using Peripheral Quantitative Computed Tomography
Timepoint [7] 342896 0
Baseline, 6 months, 12 months, 24 months, 36 months
Secondary outcome [8] 342897 0
Prostate Cancer Specific Distress will be measured using the Impact of Events Scale revised questionnaire (IES).
Timepoint [8] 342897 0
Baseline, 6 months, 12 months, 24 months, 36 months
Secondary outcome [9] 342898 0
Overall Psychological Distress will be measured using the Brief Symptom Inventory-18 (BSI-18) questionnaire.
Timepoint [9] 342898 0
Baseline, 6 months, 12 months, 24 months, 36 months
Secondary outcome [10] 342899 0
PSA Anxiety will be measured using the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) questionnaire.
Timepoint [10] 342899 0
Baseline, 6 months, 12 months, 24 months, 36 months
Secondary outcome [11] 342980 0
Physical activity levels - Physical activity levels will be assessed objectively over a 7-day period using a validated, reliable tri-axial accelerometer activity monitor (ActiGraph GT3X+). Self-reported physical activity will be assessed by the leisure score index from the Godin Leisure-Time Exercise Questionnaire.
Timepoint [11] 342980 0
Baseline, 6 months, 12 months, 24 months, 36 months

Eligibility
Key inclusion criteria
1) histologically proven adenocarcinoma of the prostate, 2) no prior therapy for PCa, 3) fit for curative intent therapy, 4) willing to attend follow-up, 5) clinical stage less than or equal to T2, 6) less than or equal to 10 % Gleason pattern 4 disease on biopsy, and 7) PSA less than or equal to 10ng/ml.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1) already performing regular exercise defined as undertaking structured resistance and aerobic training two or more times per week within the past 3 months, 2) acute illness or any musculoskeletal, cardiovascular or neurological disorder that could inhibit exercise performance or put participants at risk from exercising, 3) variant histopathology (small cell, intra-ductal, sarcomatoid), presence of extra-prostatic extension (EPE) or lympho-vascular invasion (LVI), 4) patient no longer considered a candidate for curative intent treatment, and 5) intention to move place of residence away from the two study sites.

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)
Central randomisation via web-based service
Methods used to generate the sequence in which subjects will be randomised (sequence 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
Efficacy
Statistical methods / analysis
The target sample size of 168 patients is based on having 80% power to be able to detect a hazard ratio of undergoing curative therapy in the exercise intervention group, compared with the usual care group, of 0.35 or smaller (alpha=0.05). This is equivalent to a difference between 25% of the usual care group undergoing curative therapy within 3 years post randomization vs <10% in the group undertaking the exercise intervention. A difference of this magnitude has been recommended by our practice clinicians to be clinically important. This sample size accounts for a possible 5% drop-out due to clinical records not being available at study completion. This sample size will give us sufficient power to examine our secondary outcomes of interest. For example, for muscle mass we will have >80% power to detect differences between groups of 0.8kg or greater at 6-months post-intervention, assuming a standard deviation for change of ~ 1.5 kg and 30% loss to follow-up (due to the need for participants to re-present to the study team for this outcome to be measured). The primary outcome, initiation of curative therapy, will be analysed using Cox proportional hazards regression, with treatment group (exercise intervention/usual care) entered as the main effect. If data do not meet the proportional hazards assumption, the log-rank test will be used. Outcomes measured repeatedly will be analysed using mixed effects models to examine differences between groups over time, with treatment group and time included as main effects, as well as an intervention-by-time interaction term. Patient will be included as a random effect to account for the non-independence of observations from the same participant. Continuous outcomes will be analysed using linear models, binary outcomes with logistic models and count outcomes with Poisson models. Depending on the balance between groups post-randomisation, clinically relevant covariates will be included in the models where appropriate. Data will be analysed using an intention-to-treat approach. Tests will be two-tailed and an alpha level of 0.05 will be applied as the criterion for statistical significance.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/03/2018
Actual
8/06/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
168
Accrual to date
13
Final
Recruitment in Australia
Recruitment state(s)
WA,VIC

Funding & Sponsors
Funding source category [1] 298555 0
Government body
Name [1] 298555 0
National Health and Medical Research Council (NHMRC)
Country [1] 298555 0
Australia
Primary sponsor type
University
Name
Edith Cowan University
Address
270 Joondalup Drive
Joondalup WA 6027
Country
Australia
Secondary sponsor category [1] 297705 0
None
Name [1] 297705 0
Address [1] 297705 0
Country [1] 297705 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299524 0
Edith Cowan University Human Research Ethics Committee
Ethics committee address [1] 299524 0
Ethics committee country [1] 299524 0
Australia
Date submitted for ethics approval [1] 299524 0
Approval date [1] 299524 0
09/08/2017
Ethics approval number [1] 299524 0
17072 GALVAO

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

Contacts
Principal investigator
Name 80718 0
Prof Daniel Galvão
Address 80718 0
Exercise Medicine Research Institute
Edith Cowan University
270 Joondalup Drive
Joondalup WA 6027
Country 80718 0
Australia
Phone 80718 0
+61 8 6304 3420
Fax 80718 0
Email 80718 0
d.galvao@ecu.edu.au
Contact person for public queries
Name 80719 0
Daniel Galvão
Address 80719 0
Exercise Medicine Research Institute
Edith Cowan University
270 Joondalup Drive
Joondalup WA 6027
Country 80719 0
Australia
Phone 80719 0
+61 8 6304 3420
Fax 80719 0
Email 80719 0
d.galvao@ecu.edu.au
Contact person for scientific queries
Name 80720 0
Daniel Galvão
Address 80720 0
Exercise Medicine Research Institute
Edith Cowan University
270 Joondalup Drive
Joondalup WA 6027
Country 80720 0
Australia
Phone 80720 0
+61 8 6304 3420
Fax 80720 0
Email 80720 0
d.galvao@ecu.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
Individual participant data will not be available for data dictionaries or other formats. The de-identified data will be stored within the Exercise Medicine Research Institute, in accordance with the National Statement, and earlier approval provided by the Human Research Ethics Committee of Edith Cowan University.


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
SourceTitleYear of PublicationDOI
Dimensions AICan exercise delay transition to active therapy in men with low-grade prostate cancer? A multicentre randomised controlled trial2018https://doi.org/10.1136/bmjopen-2018-022331
N.B. These documents automatically identified may not have been verified by the study sponsor.