Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000237381
Ethics application status
Approved
Date submitted
10/01/2017
Date registered
15/02/2017
Date last updated
4/09/2023
Date data sharing statement initially provided
9/06/2021
Date results information initially provided
9/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
TROG 14.04 HART: Deep Inhalation Breath Hold for reduction of cardiac toxicity in patients with left-sided breast cancer undergoing radiotherapy, HART (Heart Avoiding Radiation Therapy)
Scientific title
Deep Inhalation Breath Hold for reduction of cardiac toxicity in patients with left-sided breast cancer undergoing radiotherapy
Secondary ID [1] 290877 0
NONE
Universal Trial Number (UTN)
U1111-1188-0206
Trial acronym
TROG 14.04 HART
Linked study record

Health condition
Health condition(s) or problem(s) studied:
breast cancer 301584 0
Condition category
Condition code
Cancer 301293 301293 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The purpose of the trial is to demonstrate the feasibility to evaluate Deep Inhalation Breath Hold (DIBH) countrywide as demonstrated in patient compliance and reproducibility of set-up.

The trial is a two-arm study assessing the feasibility of DIBH during Radiotherapy treatment: the intervention group corresponds to left-sided breast cancer patients whereas the control group corresponds to right sided breast cancer patients.

Left sided breast cancer patients who do not proceed to treatment with DIBH will be included in the assessment. A control group is included to compare the reproducibility of set-up between participants treated with/without DIBH and compare resource requirements.

Patients will undergo DIBH (provided they are able to hold their breath in a reproducible and consistent manner for a long enough period, which is approximately 10 to 15 seconds). Participants with left-sided breast cancer will undergo breathing training if applicable.

There is no prescribed breathing training for participating centres as we would like to capture clinical practice. Breathing training will also depend on the equipment used to guide DIBH. The type of breathing training that is provided by the site will be captured prior to the commencement of the trial.

Most centres would provide training and according to informal discussions, this is between 20min and one hour. The training is most likely performed by radiation therapists who also oversee and conduct the planning CT scans for the patient. RTs are a registered profession. It is also common that patients undergo a ‘practice’ session prior to the CT scan where they take breaths under observation in the same way as during treatment but without either imaging or treatment delivery.

When performing the DIBH, patients are asked to take a deep breath prior to radiation delivery. This is likely to move the heart away from the high dose region aimed at breast tissue (or chest wall) thereby reducing dose to the heart. Patients will perform DIBH at every radiation delivered over the five weeks.

Each participant will complete and anxiety assessment before receiving standard of care radiotherapy treatment as per their institution's guidelines. All participants will have daily electronic portal imaging (EPI) taken during the first week of treatment and then weekly EPI for 5 weeks. During the 3rd week of radiotherapy treatment, the participants with left-sided breast cancer will complete another anxiety assessment.

As part of the trial, patients will have two planning CT scans: Free breathing and DIBH. The scheduling of the two scans is left to department practice. Patients in the control group will only have the standard CT scan used for treatment planning.

Patient follow-up will be as per institution's practice.
Intervention code [1] 296823 0
Treatment: Other
Intervention code [2] 296839 0
Prevention
Comparator / control treatment
Right sided breast cancer participants and Left sided breast cancer participants who fail DIBH to receive standard of care radiotherapy only
Control group
Active

Outcomes
Primary outcome [1] 300707 0
Primary Outcome - Feasibility of DIBH

Feasibility will be determined by three factors:
1. Favourable DIBH plan: The difference in the geometric relation between heart and target volume in free breathing and DIBH which will be assessed in the direct comparison of treatment plans developed for the two CT scans acquired for the trial. DIBH plan will be considered favourable if the target volume DVH parameters can be assumed to be clinically non-inferior, the lung DVH is better or clinically unchanged and the mean heart dose is reduced.

2. The ability of patients to hold their breath
3. Acceptable reproducibility defined as standard deviation of the mid lung distance assessed from electronic portal images acquired in the first week of treatment
Timepoint [1] 300707 0
After all participants have completed radiotherapy treatment
Primary outcome [2] 300708 0
Magnitude of the potential impact of DIBH on cardiac dose in patients undergoing radiotherapy for left-sided breast cancer

Magnitude of the potential impact of DIBH will be assessed by looking at the mean dose to the heart using DIBH RT plan and the dose to the heart using free breathing plan. The software used to develop the RT plans will measure/capture the mean dose to the heart.
Timepoint [2] 300708 0
When left-sided breast cancer participants have completed RT planning for both free breathing and DIBH.
Secondary outcome [1] 330662 0
Dosimetric differences for other organs such as lung and contralateral breast between conventional and DIBH treatment

This will be assessed by using the RT planning software to look at the dose volume parameters for the ipsilateral lung, left anterior descending artery, contralateral breast, and oesophagus using DIBH and free breathing plans.
Timepoint [1] 330662 0
When left-sided breast cancer participants have completed RT planning for both free breathing and DIBH.
Secondary outcome [2] 330663 0
Resource requirements for implementation of DIBH

Trial data collected by Case Report Forms (CRF) will be used to assess resource requirements for implementation of DIBH
Timepoint [2] 330663 0
After all participants have completed radiotherapy treatment

Eligibility
Key inclusion criteria
Females greater than or equal to 18 years
Written informed consent
Breast cancer with an indication for radiotherapy after breast conserving surgery or mastectomy
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Significant respiratory illnesses or breathing difficulties who are unable to comply with DIBH
Bilateral breast cancer

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/02/2018
Actual
20/02/2018
Date of last participant enrolment
Anticipated
1/02/2019
Actual
22/11/2018
Date of last data collection
Anticipated
10/03/2019
Actual
21/12/2018
Sample size
Target
60
Accrual to date
Final
62
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 8513 0
Gold Coast University Hospital - Southport
Recruitment hospital [2] 8514 0
Orange Health Service - Orange
Recruitment hospital [3] 8515 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 8516 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [5] 8517 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 16606 0
4215 - Southport
Recruitment postcode(s) [2] 16607 0
2800 - Orange
Recruitment postcode(s) [3] 16608 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 16609 0
3000 - Melbourne
Recruitment postcode(s) [5] 16610 0
2145 - Westmead
Recruitment outside Australia
Country [1] 9046 0
New Zealand
State/province [1] 9046 0

Funding & Sponsors
Funding source category [1] 295310 0
Other Collaborative groups
Name [1] 295310 0
Australia and New Zealand Breast Cancer Trials Group
Country [1] 295310 0
Australia
Funding source category [2] 295385 0
Charities/Societies/Foundations
Name [2] 295385 0
The Eric and Elizabeth Gross Foundation
Country [2] 295385 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Trans Tasman Radiation Oncology Group
Address
TROG Central Office
Calvary Mater Newcastle
MHA Building, Level 5
Edith St
Waratah, NSW 2298
Country
Australia
Secondary sponsor category [1] 294135 0
Other Collaborative groups
Name [1] 294135 0
Australia and New Zealand Breast Cancer Trials Group
Address [1] 294135 0
PO Box 155
HRMC NSW 2310
Country [1] 294135 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296643 0
Peter MacCallum Human Research Ethics Committee
Ethics committee address [1] 296643 0
Ethics Committee Secretariat
Peter MacCallum Cancer Centre
Level 4, 305 Grattan Street
Melbourne VIC 3000
Ethics committee country [1] 296643 0
Australia
Date submitted for ethics approval [1] 296643 0
29/06/2017
Approval date [1] 296643 0
15/08/2017
Ethics approval number [1] 296643 0
HREC/17/PMCC/83

Summary
Brief summary
The primary purpose of this trial is to evaluate whether deep inhalation breath hold (DIBH) is feasible and effective for reducing the radiation dose to the heart during radiotherapy for cancer of the left breast.

Who is it for?
You may be eligible to enroll in this trial if you are aged 18 or over and have been diagnosed with breast cancer (left or right breast) for which radiotherapy treatment is planned following breast conserving surgery or mastectomy.

Study details
There will be two groups enrolled in this trial. The first group of participants with left breast cancer who have demonstrated that they can successfully complete the DIBH for 15 secs (2 repeats) will complete the DIBH procedure at every radiotherapy delivery for 5 weeks. DIBH involves taking a deep breath in and holding that breath whilst the radiotherapy dose is delivered over approximately 10 to 15 seconds. Any left breast cancer participants who are not able to complete DIBH, plus right breast cancer participants will undergo standard radiotherapy treatment with no breath holding intervention.

It is hoped that the results of this trial will provide information on whether DIBH is feasible for patients undergoing radiotherapy, and initial information on whether the technique is effective for reducing the dose of radiation delivered to the heart.
Trial website
https://trog.com.au/1404-HART
Trial related presentations / publications
Kron T, Bressel M, Lonski P, Hill C, Mercieca-Bebber R, Ahern V, et al. TROG 14.04: Multicentre Study of Feasibility and Impact on Anxiety of DIBH in Breast Cancer Patients. Clinical Oncology. 2022;34(9):e410-e9.
Public notes

Contacts
Principal investigator
Name 71610 0
Prof Tomas Kron
Address 71610 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne VIC 3000
Country 71610 0
Australia
Phone 71610 0
+61 03 85596925
Fax 71610 0
Email 71610 0
[email protected]
Contact person for public queries
Name 71611 0
Ms Rebecca Montgomery
Address 71611 0
TROG Central Office
Calvary Mater Newcastle
Edith St
Waratah, NSW
2298
Country 71611 0
Australia
Phone 71611 0
+61 02 401 43900
Fax 71611 0
+61 02 401 43902
Email 71611 0
[email protected]
Contact person for scientific queries
Name 71612 0
Prof Tomas Kron
Address 71612 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne VIC 3000
Country 71612 0
Australia
Phone 71612 0
+61 03 85596925
Fax 71612 0
Email 71612 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Anonymised Individual Patient Data (IPD) collected during the trial. The specific IPD to be shared (e.g. all data, published data, data of primary outcomes) will be as per the submitted research proposal and as assessed as appropriate by TROG.
When will data be available (start and end dates)?
Data will be made available for request after publication of the main/final study results; no end date.

Note that there may be additional circumstances preventing TROG from sharing requested data.
Available to whom?
Researchers who submit a research proposal and TROG Data Request Application, which is assessed by TROG to have an appropriate scientific value.
Available for what types of analyses?
To achieve the aims in the approved proposal.
How or where can data be obtained?
Subject to approval by TROG Cancer Research [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
20228Study protocol    Upon request from TROG Cancer Research
20230Data dictionary    Upon request from TROG Cancer Research



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Kron T, Bressel M, Lonski P, Hill C, Mercieca-Bebb... [More Details]
Plain language summaryNo The HART trial tested the feasibility of Deep Inha... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseTROG 14.04: Multicentre Study of Feasibility and Impact on Anxiety of DIBH in Breast Cancer Patients.2022https://dx.doi.org/10.1016/j.clon.2022.05.020
N.B. These documents automatically identified may not have been verified by the study sponsor.