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Trial registered on ANZCTR


Registration number
ACTRN12612000407897
Ethics application status
Approved
Date submitted
31/01/2012
Date registered
11/04/2012
Date last updated
17/02/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Selective use of postoperative radiotherapy after mastectomy (SUPREMO)
Scientific title
SUPREMO, an MRC phase III randomised trial to assess the role of adjuvant chest wall irradiation in 'intermediate risk' operable breast cancer following mastectomy (TROG (Trans Tasman Radiation Oncology Group) 11.01)
Secondary ID [1] 279793 0
TROG 11.01
Secondary ID [2] 279894 0
ISRCTN61145589
Secondary ID [3] 279895 0
NCT00966888
Secondary ID [4] 282976 0
CDR0000642751
Secondary ID [5] 282977 0
MRC-BIG2-04
Secondary ID [6] 282978 0
EU-20943
Universal Trial Number (UTN)
Trial acronym
SUPREMO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 285713 0
Condition category
Condition code
Cancer 285895 285895 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental Arm 1: Beginning 12 weeks after mastectomy or 6 weeks after adjuvant chemotherapy, patients undergo radiotherapy 5 days a week 3-5 weeks in the absence of disease progression or unacceptable toxicity. 50Gy in 25 Fractions over 5 weeks, 1 fraction daily 5 days a week.
Intervention code [1] 284147 0
Treatment: Other
Comparator / control treatment
Active Comparator Arm 2: Patients receive standard of care and observation only (as defined by their treating institution). After completion of study therapy, patients are followed up twice in the first year, and then annually for 10 years.
Control group
Active

Outcomes
Primary outcome [1] 286392 0
Overall Survival
Timepoint [1] 286392 0
Follow up clinic visits will be made postoperatively for at least 10 years:
- for patients in the cardiac substudy who receive chemotherapy, within 3 weeks of completing chemotherapy, before radiotherapy starts
- for all patients who have received chemotherapy, at the end of the course of radiotherapy or 3 months after chemotherapy in patients not receiving radiotherapy
- for patients who have not received chemotherapy, at the end of the course of radiotherapy or 3 months after the date of mastectomy (or date of final definitive surgery, if applicable) in patients not receiving radiotherapy
- at 12, 24, 36, 48, 60, 72, 84, 96, 108, 120 months after date of mastectomy (or date of final definitive surgery, if applicable).
- if the post radiotherapy visit or equivalent visit for non-irradiated patients falls within 6 weeks of the 12 month follow-up visit, then only 1 combined visit is required
- An extra follow up visit will be required for patients participating in the cardiac substudy who receive chemotherapy
Secondary outcome [1] 295758 0
Chest Wall recurrence
Timepoint [1] 295758 0
Based on physical and clinical examination, imaging and mammograms.
Follow up clinic visits will be made postoperatively for at least 10 years:
- for patients in the cardiac substudy who receive chemotherapy, within 3 weeks of completing chemotherapy, before radiotherapy starts
- for all patients who have received chemotherapy, at the end of the course of radiotherapy or 3 months after chemotherapy in patients not receiving radiotherapy
- for patients who have not received chemotherapy, at the end of the course of radiotherapy or 3 months after the date of mastectomy (or date of final definitive surgery, if applicable) in patients not receiving radiotherapy
- at 12, 24, 36, 48, 60, 72, 84, 96, 108, 120 months after date of mastectomy (or date of final definitive surgery, if applicable).
- if the post radiotherapy visit or equivalent visit for non-irradiated patients falls within 6 weeks of the 12 month follow-up visit, then only 1 combined visit is required
- An extra follow up visit will be required for patients participating in the cardiac substudy who receive chemotherapy
Secondary outcome [2] 295759 0
Regional recurrence
Timepoint [2] 295759 0
10 Years- based on physical and clinical examination, imaging and mammograms
Secondary outcome [3] 295760 0
Disease Free survival
Timepoint [3] 295760 0
10 years- based on physical and clinical examination, imaging and mammograms
Secondary outcome [4] 295761 0
Metastasis free survival
Timepoint [4] 295761 0
10 years- based on physical and clinical examination, imaging and mammograms
Secondary outcome [5] 295762 0
Cause of Death (Breast cancer, intercurrent disease [cardiovascular and non-cardiovascular])
Timepoint [5] 295762 0
10 Years- based on physical and clinical examination, imaging and mammograms
Secondary outcome [6] 295763 0
Acute and Late Morbidity
Timepoint [6] 295763 0
10 Years - measured by the RTOG/EORTC Radiation morbidity scoring system in all patients

Eligibility
Key inclusion criteria
1. Stage II histologically confirmed unilateral breast cancer following mastectomy including the following pTNM stages:
- pT1N1M0
- pT2N1M0
- pT2N0M0 if grade III histology and/or lymphovascular invasion
- pT3N0M0.
2. Stage II histologically confirmed unilateral breast cancer following neoadjuvant systemic therapy and mastectomy, if the original clinical stage was cT1-2cN0-1M0 or cT1-2pN1(sn)M0 and with the following (ypTNM) stages after neoadjuvant systemic therapy:
- ypT1pN1M0
- ypT2pN1M0
- ypT2pN0M0 if grade III histology and/or lymphovascular invasion
- ypT0pN0 or ypT1pN0 or ypT0pN1 (pathological complete remission, or near complete remission).
- ypT2N0, independent of grade or lymphovascular invasion, of the original stage was cT3N0.
- ypT3N0M0, if original clinical staging was cT1-3cN0 M0 or cT1-3pN0 (sn) M0.
3. Unilateral invasive breast cancer that conforms to the initial clinical staging of criterion 1, but has been down-staged by neoadjuvant systemic therapy to ypT0pN0 or ypT1pN0 or ypT0pN1 (pathological complete remission, or near complete remission). If tumour stage cT3 or ypT3, then nodal status must be N0 both before and after neoadjuvant systemic therapy.
4. Undergone total mastectomy (with minimum of 1 mm clear margin of invasive cancer and DCIS) and axillary staging procedure.
5. If axillary node positive (1-3 positive nodes [including micrometastases >0.2mm less than or equal to 2mm]) then an axillary node clearance (minimum of 8 nodes removed) should have been performed. Isolated tumour cells do not count as micrometastases.
6. Axillary node negative status can be determined on the basis of either axillary clearance or axillary node sampling or sentinel node biopsy. Positive or negative nodes should be determined before the commencement of neoadjuvant systemic therapy.
7. Sentinel nodes identified in the internal mammary chain are considered pN1b or pN1c if histologically proven. Patients can be included in the trial with microscopic metastasis in the internal mammary chain detected by sentinel node biopsy, if not more than 3 tumour positive nodes in axillary lymph nodes. If not biopsied, internal mammary chain sentinel nodes are considered tumour negative for staging.
8. Before neoadjuvant systemic therapy, axillary ultrasound is advised
9. Fit for adjuvant or neoadjuvant chemotherapy (if indicated), adjuvant or neoadjuvant endocrine therapy (if indicated) and postoperative irradiation.
10. Written, informed consent.
11. Patients undergoing immediate breast reconstruction are eligible for inclusion.
12. Patients who are carriers of known pathological mutations in BRCA1 or BRCA2 genes are eligible

Neoadjuvant systemic therapy:
- Patients who have undergone mastectomy after neoadjuvant systemic therapy are eligible.
- Tumour grade, hormone receptor status and Her-2 receptor status (or HER gene amplification) should be determined on a core biopsy taken before the start of neoadjuvant systemic therapy. Lymphovascular invasion may be assessed on both the core biopsy and post treatment excision.
- T2 tumours that are cN0 and remain ypN0 after neoadjuvant systemic therapy can only be included if grade III histology and / or lymphovascular invasion.
T3 tumours can only be included if N0 both before and after neoadjuvant systemic therapy (cN0, pN0(sn), ypN0).
Minimum age
No limit
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria (patients who fulfill the following are NOT eligible for this study):
1. Any pT0pN0-1 or pT1pN0 tumours after primary surgery.
2. Any pT3pN1 or pT4 tumours. Initial stage cT3cN1 or pN1(sn) or cT4 in patients receiving neoadjuvant systemic therapy cannot be included, even if downstaging has occurred and the pathological ypT and N stage is lower.
3. Patients who have 4 or more pathologically involved axillary nodes. For the purpose of this study protocol, nodal scarring after neoadjuvant systemic therapy will be considered as evidence of previous pathological nodal involvement and count towards the total number of involved axillary nodes.
4. Past history or concurrent diagnosis of ductal carcinoma in situ (DCIS) of the contralateral breast, unless treated by mastectomy. Previous DCIS of the ipsilateral breast if treated with radiotherapy (i.e. previous DCIS treated by conservation surgery not followed by radiotherapy would be considered eligible).
5. Bilateral breast cancer. However, patients who have undergone a prophylactic contralateral mastectomy can be included, if the breast was pathologically free of invasive tumour.
6. Previous or concurrent malignancy other than non melanomatous skin cancer and carcinoma in situ of the cervix. For previous DCIS see criterion 4.
7. Male.
8. Pregnancy, at the time of radiotherapy treatment
9. Not fit for surgery, radiotherapy or adjuvant systemic therapy.
10. Unable or unwilling to give informed consent.

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)
Enrollment will be discussed at the time of consultation for radiation Therapy. The patient will be given time to consider participation before consenting to the study. Patient consent and eligibility will be recorded on the Screening Log. Trial Screening Summary Forms will be completed and sent to the Trial Coordinating Centre. Treatment allocation will be confirmed by fax and a letter will be sent to the patien's General Practitioner.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomised by permuted blocks with the block length being varied randomly to minimise the effect of entry bias.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
10/06/2008
Date of last participant enrolment
Anticipated
Actual
30/04/2013
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
1600
Accrual to date
Final
1688
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,WA
Recruitment hospital [1] 4203 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [2] 4204 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 4205 0
St Andrew's Toowoomba Hospital - Toowoomba
Recruitment hospital [4] 4206 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [5] 4207 0
Monash Medical Centre - Moorabbin campus - East Bentleigh
Recruitment hospital [6] 4208 0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
Recruitment hospital [7] 4209 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 10114 0
2560 - Campbelltown
Recruitment postcode(s) [2] 10115 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 10116 0
4350 - Toowoomba
Recruitment postcode(s) [4] 10117 0
3002 - East Melbourne
Recruitment postcode(s) [5] 10118 0
3165 - Bentleigh East
Recruitment postcode(s) [6] 10119 0
3550 - Bendigo
Recruitment postcode(s) [7] 10120 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 4077 0
United Kingdom
State/province [1] 4077 0
Country [2] 4078 0
China
State/province [2] 4078 0
Country [3] 4079 0
Japan
State/province [3] 4079 0
Country [4] 4080 0
Peru
State/province [4] 4080 0
Country [5] 4081 0
Canada
State/province [5] 4081 0
Country [6] 4082 0
Sweden
State/province [6] 4082 0
Country [7] 4083 0
Switzerland
State/province [7] 4083 0

Funding & Sponsors
Funding source category [1] 284603 0
Government body
Name [1] 284603 0
Cancer Australia
Country [1] 284603 0
Australia
Primary sponsor type
Other Collaborative groups
Name
United Kingdom (UK) Medical Research Council (MRC)
Address
Medical Research Council
14th Floor
One Kemble Street
London
WC2B 4AN
Country
United Kingdom
Secondary sponsor category [1] 283523 0
Other Collaborative groups
Name [1] 283523 0
Trans Tasman Radiation Oncology Group (TROG)
Address [1] 283523 0
Central Operations Office
Department of Radiation Oncology
Calvary Mater Newcastle
Locked Bag 7 Hunter Region Mail Centre
NSW 2310
Country [1] 283523 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295660 0
Uniting Health Care Health Human Research Ethics Committee
Ethics committee address [1] 295660 0
Ethics committee country [1] 295660 0
Australia
Date submitted for ethics approval [1] 295660 0
Approval date [1] 295660 0
09/05/2012
Ethics approval number [1] 295660 0
1205

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

Contacts
Principal investigator
Name 33679 0
Prof Ian H. Kunkler
Address 33679 0
Edinburgh Cancer Centre
Western General Hospital
Crewe Rd South
Edinburgh
EH42XU, UK
Country 33679 0
United Kingdom
Phone 33679 0
+44 131 275 7058
Fax 33679 0
Email 33679 0
NSS.isdsupremo@nhs.net
Contact person for public queries
Name 16926 0
Rebecca Montgomery
Address 16926 0
Trans Tasman Radiation Oncology Group
Central Operations Office
Department of Radiation Oncology
Calvary Mater Newcastle
Locked Bag 7
Hunter Region Mail Centre
NSW 2310
Country 16926 0
Australia
Phone 16926 0
+61 02 4014 3910
Fax 16926 0
+61 02 4014 3902
Email 16926 0
rebecca.montgomery@trog.com.au
Contact person for scientific queries
Name 7854 0
Boon Chua
Address 7854 0
TROG SUPREMO Trial Chairperson
Department of Radiation Oncology
Peter MacCallum Cancer Centre
Locked Bag 1, A'Beckett Street
Melbourne
Victoria 8006
Country 7854 0
Australia
Phone 7854 0
+61 03 9656 1111
Fax 7854 0
Email 7854 0
boon.chua@petermac.org

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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