Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000085572
Ethics application status
Approved
Date submitted
3/01/2015
Date registered
2/02/2015
Date last updated
20/11/2018
Date data sharing statement initially provided
20/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Randomised Controlled Clinical Trial of a Supervised EXErcise Program in Patients with Lymphoma treated with Chemotherapy
Scientific title
Randomised Controlled Clinical Trial to evaluate the effect of a Supervised EXErcise Program on Quality of Life and deliverability of chemotherapy in Patients with Lymphoma treated with chemotherapy.
Secondary ID [1] 285906 0
Nil
Universal Trial Number (UTN)
Trial acronym
EXEL Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma 293825 0
Condition category
Condition code
Cancer 294126 294126 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 294230 294230 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants undergo an initial assessment where an accredited exercise physiologist designs an individually tailored exercise program. Sessions are conducted twice weekly for a total of 20 sessions. All sessions are conducted within a group setting with a maximum number of 6 individuals under the guidance and supervision of an accredited exercise physiologist.
The exercise program will include both aerobic and resistance training. Although prior observational exercise intervention studies have focused on aerobic physical activity alone, our study will involve a combination of both aerobic and resistance training as the latter has been shown to have a positive effect on the performance of tasks required for everyday function.
Initial sessions will be of 20 minutes duration with 5-minute warm up and cool down periods. The sessions are classified as light in intensity with an aim to achieve 40-50% of heart rate reserve or a rate of perceived exertion (RPE) of 10-12. Subsequent sessions will gradually increase in duration (by 5 to 10 minutes) and intensity to a maximum of 45 minutes, with a 40:60 ratio of aerobic training to resistance training. It is recognized that some participants may achieve the training goals earlier but progression will adhere strictly to the American College of Sports Medicine Guidelines.

Aerobic

Aerobic exercises primarily consist of treadmill or upright/recumbent cycling. Aerobic activities are usually 5 – 15 min duration depending on Rating of Perceived Exertion (RPE) or fatigue levels. Intensity is gradually progressed i.e. speed or resistance to support cardio- respiratory improvements. Rowing or Elliptical trainers are also available and may be considered as an alternative.

Resistance Training

All major muscle groups are exercised and we utilise pin loaded weights machines to ensure safe and effective technique. The participants commence at 75% or their 1 RM score and the resistance is gradually increased and capacity/strength improves. Typically 2 – 3 sets or 10 – 12 repetitions, although can be modified by Exercise Physiologist to suit individual.
Intervention code [1] 290883 0
Treatment: Other
Intervention code [2] 290960 0
Lifestyle
Intervention code [3] 290961 0
Behaviour
Comparator / control treatment
Patients randomised to the control arm will receive standard care that includes general health education materials regarding nutrition and physical activity, both of which are published by the Cancer Council of New South Wales and are available on their website: http://www.cancer.org.au/home.htm.
Control group
Active

Outcomes
Primary outcome [1] 293929 0
Patient reported health related quality of life as assessed by EORTC QLC C-30, HADS, Fact-An, FACT-C, FSFI and IIEF
Timepoint [1] 293929 0
Baseline, 6 weeks, 12 weeks, 6 months, 12 months.
Secondary outcome [1] 312166 0
Deliverability of chemotherapy as assessed by scheduled and actual completion of prescribed chemotherapy dose and schedule.
Timepoint [1] 312166 0
At end of chemotherapy treatment.
Secondary outcome [2] 312665 0
Emotional well-being, including mood at the completion of the structured exercise program, as assessed by EORTC QLC C-30, HADS, Fact-An, FACT-C, FSFI and IIEF Patient reported health related quality of life tools.
Timepoint [2] 312665 0
Completion of exercise program

Eligibility
Key inclusion criteria
Patients with all of the following criteria will be eligible for enrolment:
a) Aged between 18 and 80 years with biopsy-proven diagnosis of lymphoma, both Hodgkin and non-Hodgkin.
b) Recommended to have systemic chemotherapy with or without external beam radiotherapy, with curative intent.
c) Need to have at least half of their recommended number of chemotherapy treatment cycles remaining.
d) ECOG level 0-2 with adequate cardio-respiratory and musculoskeletal function to participate in a regular exercise program as determined by the consultant physician/investigator.
e) Ability to read and understand the Patient Information Document and Consent Form with provision of verbal and written consent. Willingness and ability to comply with the specified intervention protocol, follow-up visits and all necessary investigations.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with any of the following criteria are not eligible for enrolment:
a) Recommended to either observation or chemotherapy with palliative intent.
b) Psychiatric disorders which impair ability to give verbal and written consent.
c) ECOG level 3-4

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
For continuous variables the demographic data will be summarised as: number, mean, standard deviation, minimum, and maximum for continuous variables for the total sample and for subgroups of baseline prognostic factors.

For categorical variables the demographic data will be summarised as tables of frequencies, and percentages for the total sample, and for subgroups of baseline prognostic factors.

The EORTC QLQ C-30 domains will be scaled to range from 0-100 where zero corresponds to the minimum possible score, and 100 to the maximum possible score.

The continuous variables, such as EORTC QLQ C-30 domains, will be analysed by analysis of covariance (ANCOVA) for repeated measurements with the baseline score as the covariate. The repeated measurements will be the scores at 6 and 12 weeks. The assumptions of the ANCOVA are that the residuals are Normally distributed with a constant variance. These assumptions will be assessed graphically. If necessary, rectification of the transformations will be applied.

The variables of: Completion of prescribed chemotherapy dose and schedule; Duration of hospitalisation; Disease status; Progress DEXA scan will be performed at the 12-month assessment will be summarised by treatment group.

The distribution of time to event variables, such as overall survival, will be graphed with Kaplan-Meier survival curves. The distributions of the treatment group will be compared with the log-rank test. The survival distributions for each treatment group will be summarised with number of patients, number of deaths, medians, and 95% CI, if the median is reached, or the proportion of patients surviving in each treatment group at 6 and 12 months post treatment. The hazard ratio and 95% CI will compare the hazard functions between the two treatment arms.

Sample size
A key consideration in determining the sample size is to ensure that the probability of a Type I error equals 0.05 under the assumption that the null hypothesis is true. In order to achieve such a property with 2 joint primary efficacy variables a Bonferroni adjustment will be applied, so the level of significance will be set to 0.025 for each of the joint primary efficacy variables.

For the EORTC QLQ C-30 physical functioning domain, the standard deviation was estimated to be 15 points on a scale from 0-100. A 15% improvement in the physical functioning domain was therefore judged to be clinically important. Given the following settings: level of significance 0.025, 2-sided test, standard deviation of 15 units, and a mean difference of 8 units, then a sample size of 89 patients per arm would provide a power of 90%. The sample size was increased by 15% to 104 to allow for early withdrawals.

The sample size calculation is similar for the 6MWT. The standard deviation is set to 100 metres with the mean difference to 60 metres, signifying a 15% improvement relative to the comparator group.

The total sample size will therefore be 208 patients.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
5/11/2014
Actual
3/11/2014
Date of last participant enrolment
Anticipated
7/11/2016
Actual
8/06/2016
Date of last data collection
Anticipated
Actual
28/06/2017
Sample size
Target
208
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3297 0
St George Hospital - Kogarah
Recruitment postcode(s) [1] 9081 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 290487 0
Hospital
Name [1] 290487 0
St George Hospital - Public
Country [1] 290487 0
Australia
Primary sponsor type
Individual
Name
Dr Fernando Roncolato
Address
St George Hospital
Gray Street,
Kogarah
NSW, 2217
Country
Australia
Secondary sponsor category [1] 289188 0
Individual
Name [1] 289188 0
Dr Yaw Chin
Address [1] 289188 0
St George Hospital
Gray Street
Kogarah NSW
2217
Country [1] 289188 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301982 0
Seslhd Human Research Ethics Commitee
Ethics committee address [1] 301982 0
Research Support Office G71
East Wing Edmund Blacket Building
Prince of Wales Hospital
Randwick NSW 2031
Ethics committee country [1] 301982 0
Australia
Date submitted for ethics approval [1] 301982 0
29/05/2014
Approval date [1] 301982 0
22/07/2014
Ethics approval number [1] 301982 0
AU/th948110

Summary
Brief summary
The EXEL study will look at the effects of combining a structured exercise program with chemotherapy in patients with lymphoma to see whether adding exercise to a chemotherapy treatment schedule can be accomplished safely and practically.

Who is it for?
You may be eligible to join this study if you are aged between 18 and 80 years and have a biopsy-proven diagnosis of lymphoma, both Hodgkin and non-Hodgkin. You should also be recommended to have systemic chemotherapy with or without external beam radiotherapy, with curative intent.

Study details
Participants in this study will be randomly (by chance) allocated to one of two groups. Participants in one group will receive standard care which includes general health education materials regarding nutrition and physical activity, in conjunction with their prescribed chemotherapy/radiotherapy treatment. Participants in the other group will undergo a structured exercise program. All participants will be asked to complete a number of questionnaires at the beginning of the study, then at the 6 week, 12 week, 6 month and 12 month (completion of the study) time points. This information will help us evaluate whether regular supervised exercise in addition to chemotherapy improves the quality of life and sense of wellbeing during and after chemotherapy.

This study will also look at whether adding an exercise program to chemotherapy helps increase the ability of patients to receive the prescribed dose of chemotherapy treatment in the required treatment time frame. A number of study procedures will be performed when you start your participation in the study. These include:

Health status assessment – your doctor will collect clinical information about your medical history and your current level of exercise. You will also be asked to complete a number of written questionnaires that look at different aspects of your wellbeing and quality of life. This will take approximately 15 minutes.

Physical examination – your blood pressure and heart rate will be checked. Your weight, height and waistline will also be measured. You will also perform three short walking, strength and balance tests. This will take approximately 15 minutes to complete.

Blood tests – this is to check the levels of different blood cells and important vitamins and minerals in your body. Your liver and kidney function, markers of inflammation and lymphoma activity and levels of immune proteins will also be assessed. This test is done only at the beginning of the study.
ECG (electrocardiogram) – this test records the electrical activity of your heart to ensure that you have a normal heart rhythm. This procedure takes about 15 minutes and is painless. This test is done only at the beginning of the study.
Bone mineral density assessment (DEXA scan) – this is a specialised X-ray scan that tests overall bone strength and risk of fractures. X-rays of two different strengths are passed through the tissues of the body and depending on the density of the tissues. This scan takes 5-10 minutes to complete and is painless. This test is done at the beginning and the end of the study.

The exercise program includes:

Aerobic

Aerobic exercises primarily consist of treadmill or upright/recumbent cycling. Aerobic activities are usually 5 – 15 min duration depending on Rating of Perceived Exertion (RPE) or fatigue levels. Intensity is gradually progressed i.e. speed or resistance to support cardio- respiratory improvements. Rowing or Elliptical trainers are also available and may be considered as an alternative.

Resistance Training

All major muscle groups are exercised and we utilise pin loaded weights machines to ensure safe and effective technique. The participants commence at 75% or their 1 RM score and the resistance is gradually increased and capacity/strength improves. Typically 2 – 3 sets or 10 – 12 repetitions, although can be modified by Exercise Physiologist to suit individual.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 53766 0
Dr Fernando Roncolato
Address 53766 0
St. George Hospital
Gray Street
Kogarah, NSW
2217
Country 53766 0
Australia
Phone 53766 0
+61 2 9113 1111
Fax 53766 0
+61 2 9113 3958
Email 53766 0
[email protected]
Contact person for public queries
Name 53767 0
Dr Fernando Roncolato
Address 53767 0
St. George Hospital
Gray Street
Kogarah, NSW
2217
Country 53767 0
Australia
Phone 53767 0
+61 2 9113 1111
Fax 53767 0
+61 2 9113 3958
Email 53767 0
[email protected]
Contact person for scientific queries
Name 53768 0
Dr Fernando Roncolato
Address 53768 0
Haematology Department
St. George Hospital
Gray Street
Kogarah, NSW
2217
Country 53768 0
Australia
Phone 53768 0
+61 2 9113 1111
Fax 53768 0
+61 2 9113 3958
Email 53768 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
TRIAL WAS DISCONTINUED


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.