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Trial registered on ANZCTR


Registration number
ACTRN12619001746123
Ethics application status
Approved
Date submitted
27/11/2019
Date registered
9/12/2019
Date last updated
9/12/2019
Date data sharing statement initially provided
9/12/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Use of ventilation techniques to improve radiotherapy dose distributions in patients with thoracic and upper abdominal tumours
Scientific title
A single institution evaluation of continuous positive air pressure to reduce respiratory tumour motion in thoracic and upper abdominal tumours
Secondary ID [1] 299942 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung cancer 315391 0
Colorectal cancer 315538 0
Kidney cancer 315539 0
Breast Cancer 315540 0
Condition category
Condition code
Cancer 313687 313687 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Continuous Positive Airway Pressure (CPAP) will be used in patients receiving stereotactic ablative body ratiotherapy (SABR) to any tumour in the lung or upper abdomen.

This will be delivered by sleep scientists, radiation therapists, radiation oncologists and medical physicists.

The patients will have CPAP at radiotherapy simulation session, in which a four dimensional computed tomography (4DCT) scan is acquired without CPAP, followed by a 4DCT acquired with CPAP. The simulation session will take approximately 30 mins. The CPAP will be applied using room air, ramping up from 4 cmH2O to a maximum pressure of 20 cmH2O, depending on participant tolerance, over a period of 5 mins. The time between 4DCT acquisitions will be the CPAP pressure ramp up time, 5 mins.

We will then measure the effect of CPAP on tumour motion based on the tumour visualised in the 4DCTs. If tumour motion is reduced with CPAP, the patient will have CPAP for the duration of each of their radiotherapy treatment sessions (1-5 sessions).
Intervention code [1] 316210 0
Treatment: Devices
Comparator / control treatment
The comparator is no CPAP.
Control group
Active

Outcomes
Primary outcome [1] 322114 0
Tumour motion (Euclidian distance between inhale and exhale phases) when CPAP is used and with free breathing as measured on 4DCTs
Timepoint [1] 322114 0
At the simulation session
Secondary outcome [1] 377398 0
Planned radiotherapy dose to organs at risk when CPAP is used and without CPAP, collected from the radiotherapy treatment plans performed on the 4DCTs acquired with and without CPAP, using the radiotherapy planning software.
Timepoint [1] 377398 0
Within 2 weeks of radiotherapy simulation
Secondary outcome [2] 377399 0
Heart motion (Euclidian distance between inhale and exhale phases) in free-breathing and CPAP 4DCTs
Timepoint [2] 377399 0
At radiotherapy simulation
Secondary outcome [3] 377400 0
Patient reported comfort/tolerance scores with CPAP measured with a likert scale.
Timepoint [3] 377400 0
At radiotherapy simulation and at the completion of all radiotherapy treatment sessions (within 4 weeks of radiotherapy simulation)
Secondary outcome [4] 377401 0
Consistency of breathing rate with and without CPAP measured by the mean and standard deviation of the breathing rate using the CT software.
Timepoint [4] 377401 0
At radiotherapy simulation

Eligibility
Key inclusion criteria
1. Age > 18
2. Has provided written informed consent for the trial
3. Receiving radiotherapy to an abdominal or thoracic tumour
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Recent (< 6 months) thoracic surgery
2. Recent (< 6 months) pneumothorax
3. Deemed unsuitable for CPAP by respiratory physician

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
It is assumed that the ratio of the tumour motion under CPAP (m_CPAP) to that under FB (m_FB) may be modelled as beta distributed and that the parameters of the beta distribution can be approximated from the pilot data from four patients from Royal North Shore Hospital. The four patients were observed to have reduced their motion by 32%, 62%, 45%, and 75% respectively (so m_CPAP/m_FB = 0.68, 0.38, 0.55, and 0.25. Using maximum likelihood estimation for the ratio m_CPAP/m_FB , this corresponds to a beta distribution with estimated parameters of a=4.17 and ß=4.80 ((µ=a)/ß=0.465, which is the expected value of m_CPAP/m_FB for the pilot data).

If CPAP reduces tumour motion relative to FB by >30% (m_CPAP/m_FB =0.7) then in combination with other likely benefits such as lung volume increase, movement of tumour baseline position away from critical structures, and more consistency in breathing, CPAP would be considered worth pursuing further. In order to be conservative we base our sample size calculation on a more ambitious null hypothesis of a 40% reduction in motion (m_CPAP/m_FB =0.6).

By simulation of data from a beta distribution with the above parameters (a=4.17 and ß=4.80, which corresponds to a true underlying m_CPAP/m_FB of 0.465), using 20,000 iterations it was found that with a 2 sided type I error rate of 5%, and, a sample size of 10 provides a power of 0.80 to reject the null hypothesis of m_CPAP/m_FB =0.6 in favour of the alternate hypothesis that m_CPAP/m_FB <0.6. A sample size of 20 provides a power of 0.975.

Analysis Plan
Radiotherapy treatment planning 4DCTs will be saved in the PMCC PACS. These will be imported into radiotherapy treatment planning software as per standard of care for these patients. The tumour will be contoured in the different phases of the CPAP and free-breathing 4DCTs, and the Euclidean distance between the inhale and exhale tumour positions (centre of mass) will be recorded in an excel spreadsheet. The per patient differences between CPAP and free-breathing will be computed, as well as the population mean, median, standard deviation, minimum and maximum. The tumour respiratory motion in the CPAP and free breathing arms will be compared using the Wilcoxon signed rank test. This will be repeated for 4DCBCT data.

The dose to organs at risk will be extracted from radiotherapy treatment planning software into an excel spreadsheet from radiotherapy treatment plans performed on the free-breathing and CPAP data sets. The free-breathing and CPAP organ at risk doses will be compared, per organ per metric, using the Wilcoxon signed rank test.

Statistical analysis – questionnaire
Quantitative questionnaire data will be exported from the study database and analysed using R. Data from each item of the questionnaire will be reported descriptively using means/standard deviations, or n/percentages as appropriate.

The O2 saturation results will be extracted into an excel spreadsheet and reviewed by a respiratory physician to determine any clinical significant deviations from normal respiratory function.

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)
VIC
Recruitment postcode(s) [1] 28667 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 304406 0
Hospital
Name [1] 304406 0
Peter MacCallum Cancer Centre
Address [1] 304406 0
305 Grattan St, Melbourne, VIC, 3000, Australia
Country [1] 304406 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan St, Melbourne, VIC, 3000, Australia
Country
Australia
Secondary sponsor category [1] 304664 0
None
Name [1] 304664 0
Address [1] 304664 0
Country [1] 304664 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304842 0
Peter MacCallum Cancer Centre Human Research Ethics Committee
Ethics committee address [1] 304842 0
Peter MacCallum Cancer Centre
305 Grattan Street Melbourne
Melbourne, Victoria
3000 Australia
Ethics committee country [1] 304842 0
Australia
Date submitted for ethics approval [1] 304842 0
07/06/2018
Approval date [1] 304842 0
20/08/2019
Ethics approval number [1] 304842 0
HREC/18/PMCC/206

Summary
Brief summary
The purpose of this study is the measure the effect of continuous positive airway pressure (CPAP) on the movement of thoracic and abdominal tumours.

Who is it for?
You may be eligible for this study if you are an adult who is receiving stereotactic ablative radiotherapy for any cancer in the abdominal or thoracic region.

Study details
All participants in this study will be asked to complete a radiotherapy simulation session where you will have a CT taken with and without CPAP. We will then measure your tumour motion from the imaging. If your tumour motion with CPAP is reduced, you will have this for your treatment sessions.

We hope that CPAP will be a well-tolerated, effective method of reducing respiratory tumour motion. This will reduce the volume of healthy organs around the tumour receiving radiation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98382 0
Dr Nicholas Hardcastle
Address 98382 0
Physical Sciences
Peter MacCallum Cancer Centre
305 Grattan St
Melbourne, VIC, 3000
Country 98382 0
Australia
Phone 98382 0
+61 385596940
Fax 98382 0
Email 98382 0
nick.hardcastle@petermac.org
Contact person for public queries
Name 98383 0
Dr Nicholas Hardcastle
Address 98383 0
Physical Sciences
Peter MacCallum Cancer Centre
305 Grattan St
Melbourne, VIC, 3000
Country 98383 0
Australia
Phone 98383 0
+61 385596940
Fax 98383 0
Email 98383 0
nick.hardcastle@petermac.org
Contact person for scientific queries
Name 98384 0
Dr Nicholas Hardcastle
Address 98384 0
Physical Sciences
Peter MacCallum Cancer Centre
305 Grattan St
Melbourne, VIC, 3000
Country 98384 0
Australia
Phone 98384 0
+61 385596940
Fax 98384 0
Email 98384 0
nick.hardcastle@petermac.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The raw data collected describing:
tumour motion with and without CPAP
Heart motion with and without CPAP
organ radiation doses in radiotherapy plans with and without CPAP
consistency of respiratory cycle with and without CPAP
When will data be available (start and end dates)?
Immediately following publication,
Start date: January 2021
End date: No end date determined
Available to whom?
anyone who wishes to access it
Available for what types of analyses?
Any purpose
How or where can data be obtained?
We will provide the data as supplementary material in the trial publication.
What supporting documents are/will be available?
No other documents available
Summary results
No Results