Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000551796
Ethics application status
Approved
Date submitted
5/05/2013
Date registered
16/05/2013
Date last updated
17/05/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
In women with breast cancer, does Accelerated Partial Breast Irradiation (APBI) demonstrate acceptable general cosmesis with an improved quality of life?
Scientific title
In women diagnosed with localised breast cancer, does Accelerated Partial Breast Irradiation (APBI) demonstrate acceptable general cosmesis with an improved quality of life?
Secondary ID [1] 282369 0
Nil known.
Universal Trial Number (UTN)
Nil.
Trial acronym
APBI Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast cancer. 288945 0
Condition category
Condition code
Cancer 289282 289282 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
We are testing the feasibility of using Accelerated Partial Breast Irradiation (APBI) to deliver adjuvant radiation to only the breast tissue surrounding the surgical excision cavity. This is different to the normal external beam radiation approach whereby the entire affected breast is treated.

The procedure involves the insertion of approximately 10 to 25 hollow plastic tubes (catheters) into the region surrounding the surgical excision cavity of the breast under general anaesthetic and ultrasound guidance. These catheters will remain in situ for 7 days.

The catheters are then connected to a computerised machine which remotely controls the movement of a high dose rate radioactive source into the catheters and determines the exact amount of radiation given (3.4Gy per fraction).

In doing so, the dose of radiation is individually tailored to target the areas which are at the highest risk of disease recurrence whilst minimising dose to the surrounding normal structures.

The treatment time is truncated from approximately 15 to 30 daily treatments for external beam radiotherapy
(depending on individual patient factors and institutional protocols) to twice daily treatments with an inter-fraction interval of at least 6 hours over 5 days in total for APBI. Each treatment lasts for 10-15mins.

It is hoped that this logistical advantage will improve the acceptability of adjuvant radiotherapy and consequently increase the numbers of women who opt for breast conservation treatment.
Intervention code [1] 287000 0
Treatment: Other
Intervention code [2] 287114 0
Treatment: Devices
Comparator / control treatment
Nil comparator. This is a Phase 2 technical feasibility trial. Multiple international Phase 2 trials with mature followup, as well as a small randomised controlled trial have demonstrated equivalence in terms of local disease recurrence and cosmetic outcomes.

Control group
Uncontrolled

Outcomes
Primary outcome [1] 289388 0
To demonstrate technical feasiblity of APBI in breast cancer women according to dosimetric parameters on the brachytherapy treatment plan.

Important dosimetric parameters such as the percent of the prescribed dose covering 90% of the PTV (D90), the volume of tissue receiving100%, 150% and 200% of the prescribed dose (V100, V150, V200 respectively), the minimum doses delivered to the 1 and 0.1 cubic centimetres of the most irradiated PTV (D1cc and D0.1cc respectively) are recorded as shown on machine.

There is currently no consensus regarding what constitutes appropriate dose homogeneity and acceptable dose contraints for surrounding normal organs for APBI. In selecting the optimal treatment plan, the following dosimetric parameters will be used as a guide:
*V150 less than or equal to 45cc but acceptable up to maximum of 70cc
*V200 less than or equal to 10cc but acceptable up to maximum of 20cc
*more than or equal to 90% of the prescription dose covering more than or equal to 90% of the PTV but acceptable down to minimum of 85% of PTV.
*The whole breast reference volume receiving more than or equal to 50% of the prescribed dose should be limited to <60%.
*Skin dose is ideally less than or equal to 70% of the prescribed reference dose but a maximum of up to 100% is acceptable.

If these dosimetric parameters are not achievable for a particular patient, then the procedure is deemed to be not technically feasible.

In addition, the following dosimetric parameters will be recorded:
*V100 and V130 of chest wall
*Minimum dose delivered to the 1 and 0.1 cubic centimetres of the irradiated lungs
*Minimum dose delivered to the 1 and 0.1 cubic centimetres of the irradiated skin
Timepoint [1] 289388 0
At point of treatment.
Secondary outcome [1] 302558 0
Assessment of treatment-related toxicities according to NCI Common Terminology Criteria for Adverse Events (CTCAE v3).

In the event of any grade 3 or 4 treatment related toxicities, the treatment will be ceased and further treatment options will be discussed with the patient and treating doctor.
Timepoint [1] 302558 0
Post irradiation - 6 weeks, 6 months, 1 year and annually up to 10 years.
Secondary outcome [2] 302559 0
Assessment of cosmetic outcomes. The EORTC Cosmetic Rating System will be used for this study.

Qualitative - 4 digital clinical photographs will be taken. Six cosmetic items will be evaluated comprising the global cosmetic result, the appearance of the surgical scar, breast size, breast shape, nipple position, shape of the areola and skin colour. The 4-point ordinal scale developed by Harris will be used, classifying cosmetic outcome as excellent, good, fair and poor.


Quantitative - Using an in-house computer software algorithm to analyse the scanned frontal view photographs, the baseline symmetry between the nipple positions will be assessed. This is performed by calculating the breast retraction assessment (BRA) and the relative BRA.
Timepoint [2] 302559 0
At point of accrual, post irradiation - 6 weeks, 6 months, 1 year and annually up to 3 years.
Secondary outcome [3] 302564 0
Assessment of Quality of Life using the EORTC core questionnaire QLQ-C30 and supplemented with the breast module questionnaire QLQ-BR23; Body Image Scale; Fatigue Scale and Hospital Anxiety and Depression scale.
Timepoint [3] 302564 0
At point of accrual, completion of APBI, post irradiation - 6 weeks, 6 months, 1 year and annually up to 3 years.
Secondary outcome [4] 302565 0
Ipsilateral breast tumour recurrence rate (IBTR) - Cytological or histological evidence of carcinoma in the ipsilateral breast.
Timepoint [4] 302565 0
At point of accrual, completion of APBI, post irradiation - 6 weeks, 6 months, 1 year and annually up to 10 years.
Secondary outcome [5] 302690 0
Regional recurrence – cytological or histological evidence of carcinoma in the ipsilateral internal mammary, supraclavicular, infraclavicular or axillary lymph nodes.
Timepoint [5] 302690 0
At point of accrual, completion of APBI, post irradiation - 6 weeks, 6 months, 1 year and annually up to 10 years.
Secondary outcome [6] 302691 0
Contralateral breast tumour recurrence (CBTR) – cytological or histological evidence of carcinoma in the contralateral breast.
Timepoint [6] 302691 0
At point of accrual, completion of APBI, post irradiation - 6 weeks, 6 months, 1 year and annually up to 10 years.
Secondary outcome [7] 302692 0
Metastatic disease recurrence – cytological or histological evidence of carcinoma consistent with a breast primary in any other area of the body aside from those that are outline above.

For skeletal or bone marrow metastases, positive bone scan and/or MRI scan is acceptable.

For central nervous system (CNS) metastases, positive CT or MRI scan is acceptable. Solitary CNS lesions will require histological confirmation.

For liver metastases, positive CT, ultrasound or MRI scan is acceptable. It is recommended that solitary liver lesions be biopsied to confirm metastastic involvement. However, if this is not possible, then serial scans must be performed to document disease progression.
Timepoint [7] 302692 0
At point of accrual, completion of APBI, post irradiation - 6 weeks, 6 months, 1 year and annually up to 10 years.
Secondary outcome [8] 302693 0
Disease free survival - Distant disease free survival is defined as the time from patient accrual to the first diagnosis of metastatic disease recurrence regardless of any intervening IBTR, regional recurrence, contralateral breast tumour recurrence or non-breast related second primary malignancy.

Timepoint [8] 302693 0
At point of accrual, completion of APBI, post irradiation - 6 weeks, 6 months, 1 year and annually up to 10 years.
Secondary outcome [9] 302698 0
Recurrence free survival - Recurrence free survival is defined as the time from patient accrual to the first diagnosis of IBTR, regional recurrence of metastatic disease recurrence, regardless of any intervening CBTR or second primary malignancy.
Timepoint [9] 302698 0
At point of accrual, completion of APBI, post irradiation - 6 weeks, 6 months, 1 year and annually up to 10 years.

Eligibility
Key inclusion criteria
a) Females more than 50 years of age.
b) Performance status 0-2.
c) Unicentric, invasive ductal carcinoma measuring 3cm in maximal diameter or less.
d) Negative surgical resection margins, defined as no tumour at the inked margins.
e) No extensive intraductal component, as defined by >25% of the invasive ductal tumour being comprised of intraductal carcinoma or ductal carcinoma in-situ being also present in the adjacent breast tissue.
f) No lymphovascular invasion.
g) No cutaneous involvement, including Paget’s disease of the nipple, oedema (peau d’orange) or inflammatory carcinoma.
h) No axillary nodal involvement on sentinel node biopsy or axillary nodal dissection.
i) No distant metastases.
j) A clearly defined surgical excision cavity and a planning target volume to whole breast volume ratio of >25%, based on the postoperative CT scan.
k) Provision of verbal and written consent, including willingness to comply with the specified treatment protocol, follow-up visits and examinations.
Minimum age
50 Years
Maximum age
80 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
a) Locally recurrent breast cancer.
b) History of concurrent or previous malignancies (except for non-melanomatous skin cancer or carcinoma in-situ of the uterine cervix).
c) Her-2 receptor positive tumours.
d) Microscopic assessment of tumour resection margins cannot be defined accurately.
e) Women who are pregnant or lactating.
f) Pre-existing connective tissue disorder such as scleroderma, systemic lupus erythematosis and dermatomyositis.
g) Patients with ipsilateral breast implants.
h) Previous radiation treatment to the ipsilateral breast or thoracic region.
i) Psychiatric or addictive disorders that preclude patients from giving informed consent.

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)
Patients for this study will be accrued from the Cancer Care Centre at St. George Hospital, Kogarah.

Potential participants will be seen as per standard practice after breast conserving surgery for consideration of
adjuvant external beam radiotherapy. As they have been previously identifed as a potential participant in the breast
multidisciplinary meeting, the consultant radiation oncologist will describe the study to them in detail and offer this as an alternative to standard treatment.

Women who are 50 years or older, with fully excised
invasive carcinomas of the breast (less than 3cm in maximal diameter), no involved axillary lymph nodes and no
distant metastatic disease will be identified and recruited by radiation oncologists.

Patients will have the study protocol explained to them (and their friends/ family members as required) in detail and
the option of having external beam radiotherapy as standard treatment will be offered to them at the same time. They will have every opportunity to ask any questions to clarify the rationale, logistics and potential toxicities of the study and are free to seek a second medical opinion elsewhere.

Patients are required to sign on consent form prior commencement of trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This is a non randomised trial.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A review of the number of breast cancer patients who satisfy the pathological criteria for APBI over the last two years at St. George Hospital have revealed an approximate number of 30 to 40 patients per year. The assumption is that 20% of these are unsuitable for eventual implantation either due to geographical location of the tumour and/or the inability to clearly visualise the surgical cavity. A further 20% of patients may not wish to participate in this trial. Hence, a figure of 18 to 24 patients per year is estimated to be accrued, with an eventual time frame of 3 years for completion.

Even though this is a feasibility study, we have opted to use early stopping rules for acute treatment-related toxicities according to the method of Mehta and Cain.

An unacceptable toxicity rate is defined by a >10% rate of grade 3 or above effects and an interim analysis will be performed after 20 and 40 patients have participated in the study. Therefore, if 5 and 8 patients had grade 3 or above treatment-related toxicities after 20 and 40 patients have been accrued respectively, then the study will be terminated.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/10/2011
Actual
8/11/2011
Date of last participant enrolment
Anticipated
31/12/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 938 0
St George Hospital - Kogarah
Recruitment postcode(s) [1] 6795 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 287156 0
Self funded/Unfunded
Name [1] 287156 0
Special Purposes & Trust fund of Dr Yaw Chin.
Country [1] 287156 0
Australia
Primary sponsor type
Individual
Name
Dr Yaw Chin.
Address
Cancer Care Centre
St George Hospital
Short Street
Kogarah NSW 2217
Country
Australia
Secondary sponsor category [1] 285921 0
None
Name [1] 285921 0
Address [1] 285921 0
Country [1] 285921 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289153 0
Cancer Institute NSW
Ethics committee address [1] 289153 0
Ethics committee country [1] 289153 0
Australia
Date submitted for ethics approval [1] 289153 0
06/09/2010
Approval date [1] 289153 0
15/11/2010
Ethics approval number [1] 289153 0
HREC/10/CIC/21

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

Contacts
Principal investigator
Name 39434 0
Dr Yaw Sinn Chin
Address 39434 0
Cancer Care Centre
St George Public Hospital
Short St
Kogarah NSW 2217
Country 39434 0
Australia
Phone 39434 0
+61-02-91131111
Fax 39434 0
Email 39434 0
yaw.chin@sesiahs.health.nsw.gov.au
Contact person for public queries
Name 39435 0
Yaw-Sinn Chin
Address 39435 0
Cancer Care Centre
St George Public Hospital
Short St
Kogarah NSW 2217
Country 39435 0
Australia
Phone 39435 0
+61-02-91131111
Fax 39435 0
Email 39435 0
yaw.chin@sesiahs.health.nsw.gov.au
Contact person for scientific queries
Name 39436 0
Yaw-Sinn Chin
Address 39436 0
Cancer Care Centre
St George Public Hospital
Short St
Kogarah NSW 2217
Country 39436 0
Australia
Phone 39436 0
+61-02-91131111
Fax 39436 0
Email 39436 0
yaw.chin@sesiahs.health.nsw.gov.au

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What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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