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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02889874




Registration number
NCT02889874
Ethics application status
Date submitted
25/08/2016
Date registered
7/09/2016
Date last updated
25/02/2019

Titles & IDs
Public title
EXamining PErsonalised Radiation Therapy for Low-risk Early Breast Cancer
Scientific title
A Randomised Phase III Trial of Adjuvant Radiation Therapy Versus Observation Following Breast Conserving Surgery and Endocrine Therapy in Patients With Molecularly Characterised Luminal A Early Breast Cancer
Secondary ID [1] 0 0
2016-003527-33
Secondary ID [2] 0 0
ANZ1601/BIG 16-02
Universal Trial Number (UTN)
Trial acronym
EXPERT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early Stage Breast Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Omission of radiation therapy

No Intervention: A: Radiation Therapy & endocrine therapy - Patients randomized to Arm A will receive standard radiation therapy and adjuvant endocrine therapy (standard of care).

Experimental: B: No Radiation Therapy (ET only) - Patients randomized to Arm B will not receive radiation therapy (omission of radiation therapy) and receive adjuvant endocrine therapy only.


Treatment: Other: Omission of radiation therapy
Omission of radiation therapy (adjuvant endocrine therapy only).

Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Local recurrence rate after breast conserving surgery - The time from randomisation to the date of local recurrence (LR) as a site of first recurrence.
Timepoint [1] 0 0
10 years
Secondary outcome [1] 0 0
Local-regional recurrence-free interval (LRRFI) - Time from randomisation to the date of local or regional recurrence as a site of first recurrence.
Timepoint [1] 0 0
10 years
Secondary outcome [2] 0 0
Distant recurrence-free interval (DRFI) - Time from randomisation to the date of distant recurrence, regardless of occurrence of any intervening local or regional recurrence, contralateral breast cancer or second (non-breast) primary invasive cancer.
Timepoint [2] 0 0
10 years
Secondary outcome [3] 0 0
Disease free survival including DCIS (DFS-DCIS) - Time from randomisation to date of first evidence of local (invasive breast carcinoma or DCIS), regional or distanct recurrence; contralateral breast cancer (invasive breast carcinoma or DCIS); second (non-breast) primary invasive cancer; or death.
Timepoint [3] 0 0
10 years
Secondary outcome [4] 0 0
Invasive disease free survival (iDFS) - Time from randomisation to date of first evidence of local (invasive breast carcinoma), regional or distanct recurrence; contralateral breast cancer (invasive breast carcinoma); second (non-breast) primary invasive cancer; or death.
Timepoint [4] 0 0
10 years
Secondary outcome [5] 0 0
Recurrence-free interval - Time from randomisation to the date of local, regional or distant recurrence as a site of first recurrence.
Timepoint [5] 0 0
10 years
Secondary outcome [6] 0 0
Overall survival (OS) - Time from randomisation to date of death from any cause.
Timepoint [6] 0 0
10 years
Secondary outcome [7] 0 0
Salvage RT or mastectomy rate - Time from randomisation to the receipt of salvage RT or mastectomy, individually and in combination (one or the other) as a composite endpoint.
Timepoint [7] 0 0
10 years
Secondary outcome [8] 0 0
Adverse events for patients - Adverse events during treatment (up to 5 years of endocrine therapy) assessed using NCI CTCAE v4.0.
Timepoint [8] 0 0
5 years
Secondary outcome [9] 0 0
Assessment of the impact of endocrine therapy - FACT-ES measure of endocrine symptoms.
Timepoint [9] 0 0
5 years

Eligibility
Key inclusion criteria
for registration in the study:

1. Female patients aged = 50 years of any menopausal status.

2. Primary tumour characteristics as assessed by conventional histopathology:

- Unifocal histologically confirmed invasive breast carcinoma

- Maximum microscopic size =2 cm

- Grade 1 or 2 histology

- ER and PR positive in =10% of tumour cells in either the biopsy or breast
conserving surgical specimen

- HER2 negative on IHC (score 0 or 1+) or in situ hybridisation
(ERBB2-amplification Ratio ERBB2/centromeres <2.0 or mean gene copy number <6).
Equivocal IHC score (2+) must be assessed by ISH.

3. Primary tumour must be resected by breast conserving surgery with microscopically
negative margins for invasive carcinoma and any associated ductal carcinoma in situ
(no cancer cells adjacent to any inked edge/surface of specimen) or re-excision
showing no residual disease.

4. Histologically confirmed negative nodal status determined by sentinel node biopsy or
axillary dissection. Patients with pN0 (i+) disease are eligible for study
participation (malignant cells =0.2 mm in regional lymph node(s) detected by
hematoxylin-eosin (H&E) stain or IHC, including isolated tumour cells).

5. No evidence of distant metastasis.

6. Eligible for and willing to have adjuvant endocrine therapy.

7. ECOG performance status 0-2.

8. Availability of FFPE tumour block for Prosigna (PAM50) Assay.

For randomization to the study, patients must fulfill all of the following criteria:

1. Primary tumour characteristics as assessed by Prosigna (PAM50) Assay:

- Luminal A intrinsic subtype

- ROR score =60
Minimum age
50 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Any one of the following is regarded as a criterion for exclusion from the study:

1. Primary tumour characteristics:

- Presence of multifocal or multicentric invasive carcinoma or ductal carcinoma in
situ;

- Evidence of clinical or pathologic T4 disease (extension to the chest wall,
oedema or ulceration of skin, satellite skin nodules, inflammatory carcinoma);

- The invasive component of the primary tumour is present as micro-invasion only;

- Grade 3 histology;

- Presence of lymphovascular invasion

2. Contra-indication or unwillingness to have adjuvant endocrine therapy.

3. Planned to receive adjuvant chemotherapy or biologic therapy after breast cancer
surgery, i.e. any systemic therapy other than endocrine therapy is not permitted. Any
therapy unrelated to cancer is permitted at the discretion of investigators.

4. Treated with neoadjuvant endocrine therapy, chemotherapy or biologic therapy prior to
breast cancer surgery.

5. Prior breast or thoracic RT for any condition.

6. Pre-operative breast imaging evidence of disease aside from the primary carcinoma
resected by breast conserving surgery.

7. Concurrent invasive breast carcinoma or ductal carcinoma in situ (synchronous or
metachronous).

8. Prior diagnosis of invasive breast carcinoma or ductal carcinoma in situ in either
breast irrespective of disease free interval.

9. A diagnosis of non-breast malignancy <5 years prior to randomisation with the
following exceptions:

- Patients who are diagnosed with carcinoma in situ of cervix, endometrium or
colon; melanoma in situ; and basal or squamous cell carcinoma of the skin at any
time prior to randomisation are not excluded from study participation.

- Patients who are diagnosed with other non-breast malignancy =5 years prior to
randomisation and without evidence of disease recurrence are not excluded from
study participation.

10. Significant comorbidity precluding definitive RT for breast cancer (e.g.
cardiovascular or pulmonary disease, scleroderma, systemic lupus erythematosus).

11. Life expectancy <10 years.

12. Documented mutation of BRCA1, BRCA2 or TP53, or at high genetic risk of breast cancer.

13. Pregnant or lactating patients.

14. Inability to be registered to the study =8 weeks after the last surgical procedure for
breast cancer.

15. Inability to commence RT (if randomised to receive RT) no later than 12 weeks from the
last surgical procedure for breast cancer.

16. Inability to provide written informed consent.

17. Psychiatric, addictive, or any disorder that precludes compliance with protocol
requirements.

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
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
ACT,NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
The Canberra Hospital - Canberra
Recruitment hospital [2] 0 0
Macarthur Cancer Therapy Centre - Campbelltown
Recruitment hospital [3] 0 0
St Vincent's Hospital, Sydney - Darlinghurst
Recruitment hospital [4] 0 0
Genesis Cancer Care Newcastle - Gateshead
Recruitment hospital [5] 0 0
Gosford Hospital - Gosford
Recruitment hospital [6] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [7] 0 0
Mater Hospital Sydney - North Sydney
Recruitment hospital [8] 0 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [9] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [10] 0 0
Tamworth Rural Referral Hospital - Tamworth;
Recruitment hospital [11] 0 0
Westmead Hospital - Westmead
Recruitment hospital [12] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [13] 0 0
Genesis Cancer Care Wesley - Auchenflower
Recruitment hospital [14] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [15] 0 0
Peter MacCallum Cancer Centre - Bendigo - Bendigo
Recruitment hospital [16] 0 0
Peter MacCallum Cancer Centre - Moorabin - Bentleigh East
Recruitment hospital [17] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [18] 0 0
Icon Cancer Centre Richmond - East Melbourne
Recruitment hospital [19] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [20] 0 0
GenesisCare Radiation Oncology Centre Frankston - Frankston
Recruitment hospital [21] 0 0
University Hospital Geelong - Geelong
Recruitment hospital [22] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [23] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [24] 0 0
Ringwood Radiation Oncology Centre - Ringwood East
Recruitment hospital [25] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2605 - Canberra
Recruitment postcode(s) [2] 0 0
2560 - Campbelltown
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
2290 - Gateshead
Recruitment postcode(s) [5] 0 0
2250 - Gosford
Recruitment postcode(s) [6] 0 0
1871 - Liverpool
Recruitment postcode(s) [7] 0 0
2060 - North Sydney
Recruitment postcode(s) [8] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [9] 0 0
2031 - Randwick
Recruitment postcode(s) [10] 0 0
2340 - Tamworth;
Recruitment postcode(s) [11] 0 0
2145 - Westmead
Recruitment postcode(s) [12] 0 0
2500 - Wollongong
Recruitment postcode(s) [13] 0 0
4066 - Auchenflower
Recruitment postcode(s) [14] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [15] 0 0
3550 - Bendigo
Recruitment postcode(s) [16] 0 0
3165 - Bentleigh East
Recruitment postcode(s) [17] 0 0
3128 - Box Hill
Recruitment postcode(s) [18] 0 0
3002 - East Melbourne
Recruitment postcode(s) [19] 0 0
3065 - Fitzroy
Recruitment postcode(s) [20] 0 0
3199 - Frankston
Recruitment postcode(s) [21] 0 0
3220 - Geelong
Recruitment postcode(s) [22] 0 0
3084 - Heidelberg
Recruitment postcode(s) [23] 0 0
8006 - Melbourne
Recruitment postcode(s) [24] 0 0
3135 - Ringwood East
Recruitment postcode(s) [25] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Christchurch
Country [2] 0 0
New Zealand
State/province [2] 0 0
Hamilton
Country [3] 0 0
New Zealand
State/province [3] 0 0
Palmerston North
Country [4] 0 0
New Zealand
State/province [4] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Other
Name
Breast Cancer Trials, Australia and New Zealand
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Breast International Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
International Breast Cancer Study Group
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomised, phase III, non-inferiority trial evaluating radiation therapy versus
observation following breast conserving surgery and planned endocrine therapy in patients
with stage I breast cancer of luminal A subtype defined using the Prosigna (PAM50) Assay.
Trial website
https://clinicaltrials.gov/show/NCT02889874
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Phillipa Lee
Address 0 0
Breast Cancer Trials, Australia and New Zealand
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Heath Badger
Address 0 0
Country 0 0
Phone 0 0
+61 2 4925 5239
Fax 0 0
Email 0 0
expert@bctrials.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02889874