Condition category
Cancer
Date applied
23/06/2005
Date assigned
29/07/2005
Last edited
16/11/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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 measures

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

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

private sector organisation

Funding Body Subtype

other non-profit

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

16/11/2016: No publications found, verifying study status with principal investigator. 21/01/2013: the following changes were made to the trial record: 1. Belgium, China, France, Germany, Ireland, Israel, Japan, The Netherlands, New Zealand, Poland, Singapore, Spain, Switzerland, and Turkey were added to the countries of recruitment. 2. The target number of participants was changed from 3700 to 1600.