Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Prof Ian Kunkler
ORCID ID
Contact details
Edinburgh Cancer Centre
Western General Hospital
Crewe Road
Edinburgh
EH4 2XU
United Kingdom
+44 (0)131 537 2214
i.kunkler@ed.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
G0400170
Study information
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
Acronym
SUPREMO
Study hypothesis
To determine the effect of ipsilateral chest wall irradiation following mastectomy and axillary clearance for women with operable breast cancer at 'intermediate risk' of loco-regional recurrence.
Ethics approval
Fife and Forth Valley Research Ethics Committee, 04/10/2005, ref: 05/S0501/106
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Patient information can be found at: http://www.supremo-trial.com/summary-of-trial.asp
Condition
Breast cancer
Intervention
Chest wall irradiation versus no chest wall irradiation
Intervention type
Other
Phase
Phase III
Drug names
Primary outcome measure
Overall survival
Secondary outcome measures
Current secondary outcome measures as of 21/01/2013:
1. Chest wall recurrence
2. Regional recurrence
3. Disease free survival
4. Metastasis free survival
5. Cause of death (breast cancer, intercurrent disease [cardiovascular and non-cardiovascular])
6. Acute and late morbidity
7. Quality of life
8. Cost effectiveness
Previous secondary outcome measures until 21/01/2013:
1. Disease free survival
2. Metastasis free survival
3. Cause of death
4. Acute and late morbidity
5. Quality of Life
6. Cost effectiveness
Overall trial start date
01/10/2005
Overall trial end date
28/11/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current inclusion criteria as of 21/01/2013:
1.1 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.
If the tumour area comprises multiple small adjacent foci of invasive carcinoma then overall maximum dimension is taken to determine the size for T staging (see section 7.2.2 for a more detailed explanation). Multifocal or multicentric tumours can be included (pT1m; pT2m; pT3m). The size of the largest tumour focus determines the T stage classification. See section 7.2.1).
1.2 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, if the original clinical stage was cT3N0.
ypT3N0M0, if original clinical staging was cT1-3cN0 M0 or cT1-3pN0 (sn) M0.
1.3 Unilateral invasive breast cancer that conforms to the initial clinical staging of criterion 1, but has been down-staged by neoadjuvant systemic therapy to ypT0 pN0 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.
2. Undergone total mastectomy (with minimum of 1 mm clear margin of invasive cancer and DCIS) and axillary staging procedure.
3.1 If axillary node positive (1-3 positive nodes [including micrometastases >0.2mm-≤2mm]) then an axillary node clearance (minimum of 8 nodes removed) should have been performed. Isolated tumour cells do not count as micrometastases.
3.2 Axillary node negative status can be determined on the basis of either axillary clearance or axillary node sampling or sentinel node biopsy.
3.3 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.
3.4 Before neoadjuvant systemic therapy, axillary ultrasound is advised. Abnormal axillary nodes based on imaging (mammogram or ultrasound) should be sampled by guided needle sampling or core biopsy. Where axillary ultrasound is normal, negative axillary node status does not require histological confirmation before starting neoadjuvant systemic therapy. Positive, or negative, nodal status may also be determined by sentinel node biopsy before start of neoadjuvant therapy.
4. Fit for adjuvant or neoadjuvant chemotherapy (if indicated), adjuvant or neoadjuvant endocrine therapy (if indicated) and postoperative irradiation.
5. Written, informed consent.
Previous inclusion criteria until 21/01/2013:
1. pT1, pN1, M0 or pT2, N0-1, M0 unilateral histologically confirmed invasive breast cancer
2. Unifocal invasive breast cancer
3. Fit for adjuvant therapy, adjuvant endocrine therapy and postoperative irradiation
4. Undergone simple mastectomy and an axillary staging procedure
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
1600
Participant exclusion criteria
Current exclusion criteria as of 21/01/2013:
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.
Previous exclusion criteria until 21/01/2013:
1. Undergone neoadjuvant systemic therapy
2. Previous or concurrent malignancy
3. Male sex
4. Pregnancy
5. Bilateral breast cancer
6. Known BCRA1 and BCRA2 carriers
Recruitment start date
01/10/2005
Recruitment end date
28/11/2014
Locations
Countries of recruitment
Australia, Belgium, China, France, Germany, Ireland, Israel, Japan, Netherlands, New Zealand, Poland, Singapore, Spain, Switzerland, Turkey, United Kingdom
Trial participating centre
Western General Hospital
Edinburgh
EH4 2XU
United Kingdom
Sponsor information
Organisation
University of Edinburgh, Lothian Health Board and the Common Services Agency (UK)
Sponsor details
Dr Douglas Young MBA
Commercial Research Manager
Research and Development Office
NHS Lothian-University Hospitals Division
The Royal Infirmary of Edinburgh
51 Little France Crescent
Old Dalkeith Road
Edinburgh
EH16 4SA
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Research council
Funder name
Medical Research Council (UK) (G0400170)
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/30337220