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Trial registered on ANZCTR


Registration number
ACTRN12621001410842
Ethics application status
Approved
Date submitted
1/09/2021
Date registered
20/10/2021
Date last updated
20/10/2021
Date data sharing statement initially provided
20/10/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Phase II Clinical Trial of Hyper-Accelerated Partial Breast Radiotherapy in Women with Invasive Non-Lobular Breast Carcinoma
Scientific title
Phase II Clinical Trial of the Feasibility of Hyper-Accelerated Partial Breast Radiotherapy in Women with Invasive Non-Lobular Breast Carcinoma
Secondary ID [1] 305138 0
Nil known
Universal Trial Number (UTN)
Trial acronym
HEARTBEAT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early stage breast cancer 323385 0
Condition category
Condition code
Cancer 321019 321019 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Brachytherapy involves catheter implantation and delivery of internal radiotherapy to a portion of the affected breast. Radiation oncologist is the doctor responsible for this intervention procedure.
Specifically, patient will undergo catheter insertion under general anaesthetic. With ultrasound guidance, approximately 15 to 30 catheters will be inserted into the high risk area of the affected breast.
After discharge from surgery recovery, patient will have a chest CT scan to generate an appropriate treatment plan.
Subsequently delivery of the radiation will start by connecting the catheters to the brachytherapy machine via transfer tubes. Patient will be by herself inside the treatment room and will be carefully monitored with closed circuit television and microphones. Treatment will then take approximately 5 to 10 minutes.
Overall, the prescribed radiation dose is 22.5 Gy in 3 fractions, which means there will be three treatment doses to be delivered over two days. Patient do not need to be admitted to hospital during this time unless the radiation oncologist feels that it is medically necessary.
After completing the three treatment doses, the catheters will be cut and removed. Patient has completed the brachytherapy.
Intervention code [1] 321593 0
Treatment: Other
Intervention code [2] 321778 0
Treatment: Devices
Comparator / control treatment
Single group trial. No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328801 0
Compliance with dosimetric parameters assessed using 3-D treatment planning software (Oncentra Brachy)
Timepoint [1] 328801 0
Compliance with dosimetric parameters will be assessed at the time of treatment planning post catheters implantation.
Primary outcome [2] 329039 0
Non-inferiority rate of ipsilateral breast tumour recurrence (IBTR) assessed by comparing to the control group of patients from the GEC-ESTRO trial. The IBTR data is collected by clinical follow-up with patients.
Timepoint [2] 329039 0
IBTR will be assessed at 5 years timepoint post-intervention completion.
Secondary outcome [1] 400423 0
The rate of acute treatment-related toxicities assessed in accordance with the Common Terminology Criteria for Adverse Events (CTCAE5.0).
Timepoint [1] 400423 0
Acute treatment-related toxicities will be assessed at 6 weeks and 6 months post-intervention completion.
Secondary outcome [2] 400426 0
The rate of late treatment-related toxicities assessed in accordance with the Common Terminology Criteria for Adverse Events (CTCAE5.0).
Timepoint [2] 400426 0
Late treatment-related toxicities will be assessed annually for 10 years post-intervention completion.
Secondary outcome [3] 400430 0
The rate of ipsilateral regional nodal recurrence assessed by clinical examination and mammogram scan.
Timepoint [3] 400430 0
Clinical examination assessed at 6 weeks and 6 months post-intervention completion. Both clinical examination and mammogram scan will then be assessed annually for 10 years post-intervention completion.
Secondary outcome [4] 400440 0
The rate of distant metastatic disease recurrence assessed by clinical examination and imaging tests specific to the site of metastatic event.
Timepoint [4] 400440 0
Clinical examination assessed at 6 weeks, 6 months and then annually for 10 years post-intervention completion. Specific imaging tests are required at the time of suspicious metastatic disease,
Secondary outcome [5] 400441 0
Cosmetic outcome assessed by clinical examination and photographs.
Timepoint [5] 400441 0
Clinical examination and photographs are assessed at baseline, 6 weeks, 6 months and then annually for 3 years post-intervention completion.
Secondary outcome [6] 400442 0
Health-related quality of life assessed by using the questionnaires of EORTC QLQ C30 & BR-23, Breast Cancer Treatment Outcome Scale-12 (BCTOS-12), Body Image Scale (BIS), Revised Piper Fatigue Scale and Hospital Anxiety and Depression Scale (HADS). These questionnaires are considered together to form a composite secondary outcome score.
Timepoint [6] 400442 0
Assessed at baseline, 6 weeks, 6 months, and then annually for 5 years post-intervention completion.
Secondary outcome [7] 400443 0
Distant disease free survival assessed by clinical examination and tests specific to the site of distant disease.
Timepoint [7] 400443 0
Clinical examination assessed at 6 weeks, 6 months and then annually for 10 years post-intervention completion. Specific tests are required at the time of suspicious distant disease.
Secondary outcome [8] 400444 0
Recurrence free survival assessed by clinical examination and mammogram scan.
Timepoint [8] 400444 0
Clinical examination assessed at 6 weeks and 6 months post-intervention completion. Both clinical examination and mammogram scan will then be assessed annually for 10 years post-intervention completion.
Secondary outcome [9] 401267 0
Overall survival assessed by study follow-ups.
Timepoint [9] 401267 0
Overall survival follow-ups assessed at 6 weeks, 6 months, and then annually for 10 years post-intervention completion.
Secondary outcome [10] 401268 0
To identify potential biomarkers of local disease recurrence assessed using laboratory analysis of peripheral blood and resected tumour specimen.
Timepoint [10] 401268 0
Blood samples collected at baseline, 6 weeks, 6 months, 1 year, 5 years and 10 years post intervention completion. Tumour specimen collected from surgical resection at the time of local disease recurrence.

Eligibility
Key inclusion criteria
a) Women, aged 40 years and above.
b) Performance status 0-2.
c) Unicentric, invasive breast carcinoma of non-lobular histology with a maximal microscopic dimension of less than or equal to 3cm.
d) Treated with breast conserving surgery.
e) Bilateral breast imaging with mammograms and ultrasound scans no longer than 3 months prior to surgery.
f) Negative radial resection margins either from primary excision or re-excision, defined as:
• no tumour at inked margin for the invasive tumour component and
• greater than or equal to 2mm from the inked margin for the associated intraductal tumour component.
Patients with positive resection margins at either superficial or deep margins are still eligible if the surgeon confirms that all intervening breast tissue has been removed from the subcutaneous tissue or the pectoralis fascia.
g) No extensive intraductal component (EIC), defined as intraductal component constituting greater than or equal to 25% of the primary tumour with intraductal foci and/or adjacent to the primary tumour.
h) No lymphovascular invasion (LVI), defined as carcinoma cells present within a definite, endothelial-lined space (lymphatic and/or blood vessel), in peri-tumoural tissues.
Possible or suspicious LVI, defined as carcinoma cells present within a space with the appearance of a vessel but without a recognisable endothelial lining, is allowed.
i) No cutaneous involvement, including Paget’s disease of the nipple, oedema (peau d’orange), satellite skin nodules, skin ulceration or inflammatory carcinoma.
j) Oestrogen receptor positive.
k) Human epidermal growth factor receptor 2 (HER-2) negative, as determined by immunohistochemistry (IHC) staining and/or dual in-situ hybridisation (D-ISH) techniques.
l) Negative axillary lymph node involvement on histopathology, classified as either:
• no tumour cells OR
• isolated tumour cells (ITC), defined by a single or cluster of tumour cells, no larger than 0.2mm in maximal dimension.
m) Clearly defined surgical excision cavity on both assessment ultrasound and computed tomography (CT) scans.
n) Ratio of excision cavity volume to the whole breast volume less than or equal to 25%, defined on the assessment CT scan.
o) Willingness to give written informed consent.
p) Willingness to participate and comply with the study protocol.
Minimum age
40 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
a) Multifocal or multicentric breast cancer.
b) Inability to determine microscopic resection margins of the primary breast cancer.
c) Locally recurrent breast cancer.
d) History of prior malignancies, except for non-melanomatous skin cancer, carcinoma in-situ of the uterine cervix or contralateral invasive non-lobular breast cancer.
e) Pre-existing connective tissue disorder, such as scleroderma, systemic lupus erythematosis and dermatomyositis.
f) Prior radiation treatment to the ipsilateral breast or thoracic region.
g) Women who are lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study.
h) Patients with a history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study.
i) Patients who are unwilling to have their blood or tissue samples collected and stored for further genetic testing.

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
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Using the Sealed Envelope online power calculator a sample size of 608 patients is required. To account for a drop-out rate of 5%, a total number of 640 patients need to be recruited.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
11/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
640
Accrual to date
12
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20447 0
St George Hospital - Kogarah
Recruitment postcode(s) [1] 35216 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 309531 0
Hospital
Name [1] 309531 0
St George Hospital
Country [1] 309531 0
Australia
Primary sponsor type
Government body
Name
South Eastern Sydney Local Health District
Address
Gray Street, Kogarah NSW 2217
Country
Australia
Secondary sponsor category [1] 310516 0
None
Name [1] 310516 0
Address [1] 310516 0
Country [1] 310516 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309313 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 309313 0
Ethics committee country [1] 309313 0
Australia
Date submitted for ethics approval [1] 309313 0
06/11/2020
Approval date [1] 309313 0
25/11/2020
Ethics approval number [1] 309313 0
2019/ETH13365

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

Contacts
Principal investigator
Name 113722 0
Dr Yaw Chin
Address 113722 0
Cancer Care Centre, St George Hospital
1 Short Street, Kogarah NSW 2217
Country 113722 0
Australia
Phone 113722 0
+61 02 91133916
Fax 113722 0
Email 113722 0
Yaw.Chin@health.nsw.gov.au
Contact person for public queries
Name 113723 0
Dan Lu
Address 113723 0
Cancer Care Centre, St George Hospital
1 Short Street, Kogarah NSW 2217
Country 113723 0
Australia
Phone 113723 0
+61 02 91134825
Fax 113723 0
Email 113723 0
Dan.Lu@health.nsw.gov.au
Contact person for scientific queries
Name 113724 0
Yaw Chin
Address 113724 0
Cancer Care Centre, St George Hospital
1 Short Street, Kogarah NSW 2217
Country 113724 0
Australia
Phone 113724 0
+61 02 91134825
Fax 113724 0
Email 113724 0
Yaw.Chin@health.nsw.gov.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 not to be shared in public


What supporting documents are/will be available?

Current supporting documents:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
13066Study protocol  Dan.Lu@health.nsw.gov.au
13067Informed consent form  Dan.Lu@health.nsw.gov.au
13068Ethical approval  Dan.Lu@health.nsw.gov.au


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
13066Study protocol  alisar.kanjrawi@health.nsw.gov.au
13067Informed consent form  alisar.kanjrawi@health.nsw.gov.au
13068Ethical approval  alisar.kanjrawi@health.nsw.gov.au

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseExtreme hypofractionation in radiation therapy for patients with early breast cancer: what is the optimal technique?.2022https://dx.doi.org/10.1002/jmrs.590
N.B. These documents automatically identified may not have been verified by the study sponsor.