Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Dr Amit Goyal
ORCID ID
http://orcid.org/0000-0002-2381-8337
Contact details
Royal Derby Hospital
Derby
DE22 3NE
United Kingdom
+44 (0)1332 785538
amit.goyal@nhs.net
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
16069 RD-5103-001-13
Study information
Scientific title
POSNOC - POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy. A randomized controlled trial of axillary treatment in women with early stage breast cancer who have metastases in one or two sentinel nodes
Acronym
POSNOC
Study hypothesis
Current study hypothesis as of 14/06/2019:
The hypothesis of the POSNOC trial is that low axillary tumour burden patients with macrometastases in 1 or 2 sentinel nodes, receiving systemic therapy, would have non-inferior outcomes whether they are randomised to adjuvant therapy alone or adjuvant therapy plus axillary treatment (either axillary node clearance or axillary radiotherapy).
Previous hypothesis:
The hypothesis of the POSNOC trial is that low axillary tumour burden patients (clinically and ultrasound node negative) with macrometastases in 1 or 2 sentinel nodes, receiving systemic therapy, would have non-inferior outcomes whether they are randomised to adjuvant therapy alone or adjuvant therapy plus axillary treatment (axillary node clearance or axillary radiotherapy).
Ethics approval
Nottingham Research Ethics Committee 2, 13/EM/0459, First REC approval date 02/01/2014
Study design
Pragmatic randomised multi-centre non-inferiority trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Available in resources and publications section of trial website http://www.posnoc.co.uk/
Condition
Breast Cancer
Intervention
Current interventions as of 14/06/2019:
The trial interventions are either:
1. Adjuvant therapy alone (intervention)
Axillary radiotherapy is not allowed when randomised to this group.
2. Adjuvant therapy plus axillary treatment (standard care)
Axillary treatment can be either axillary node clearance or axillary radiotherapy as per local guidelines.
All participants will have adjuvant therapy according to local guidelines. Adjuvant therapy will include chemotherapy and/or endocrine therapy for all women, and radiotherapy to breast or chest wall if indicated. Human epidermal growth factor receptor 2 (HER2) targeted treatment may be administered when indicated.
Previous interventions:
The trial interventions are either:
1. Adjuvant therapy alone (intervention)
Axillary and supraclavicular fossa radiotherapy is not allowed when randomised to this group.
2. Adjuvant therapy plus axillary treatment (standard care)
Axillary treatment can be axillary node clearance or axillary radiotherapy as per local guidelines.
All participants will have adjuvant therapy according to local guidelines. Adjuvant therapy will include chemotherapy and/or endocrine therapy for all women, and radiotherapy to breast or chest wall if indicated. Human epidermal growth factor receptor 2 (HER2) targeted treatment may also be administered when indicated.
Intervention type
Drug
Phase
Phase III
Drug names
Primary outcome measure
Axillary recurrence; Timepoint(s): at 5 years
Secondary outcome measures
1. Anxiety; Timepoint(s): assessed at 3, 6, 12, 24, 36 months
2. Arm morbidity; Timepoint(s): assessed at 3, 6, 12, 24 and 36 months
3. Axillary recurrence free survival; Timepoint(s): assessed at 6, 12, 24, 36, 48 and 60 months
4. Contralateral breast cancer; Timepoint(s): assessed at 6, 12, 24, 36, 48 and 60 months
5. Disease free survival; Timepoint(s): assessed at 6, 12, 24, 36, 48 and 60 months
6. Distant metastasis; Timepoint(s): assessed at 6, 12, 24, 36, 48 and 60 months
7. Economic evaluation; Timepoint(s): assessed at 3, 6, 12, 24, 36 months
8. Local (breast or chest wall) recurrence; Timepoint(s): assessed at 6, 12, 24, 36, 48 and 60 months
9. Non-breast malignancy; Timepoint(s): assessed at 6, 12, 24, 36, 48 and 60 months
10. Overall survival; Timepoint(s): assessed at 6, 12, 24, 36, 48 and 60 months
11. Quality of life; Timepoint(s): assessed at 3, 6, 12, 24, 36 months
12. Regional (nodal) recurrence; Timepoint(s): assessed at 6, 12, 24, 36, 48 and 60 months
13. Time to axillary recurrence; Timepoint(s): assessed at 6, 12, 24, 36, 48 and 60 months
Overall trial start date
01/01/2014
Overall trial end date
31/12/2026
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current inclusion criteria as of 14/06/2019:
Women will be eligible for inclusion only if ALL of the following criteria apply:
1. 18 years or older
2. Unifocal or multi-focal invasive tumour with lesion ≤5 cm in its largest dimension, measured pathologically or largest invasive tumour diameter on radiology should be used for women who are randomised intra-operatively or undergo sentinel node biopsy before neoadjuvant therapy (tumour size should be based only on the single largest tumour; do not add the sizes together from the multiple foci)
3. At sentinel node biopsy have 1 or 2 nodes with macrometastases (tumour deposit >2.0mm in largest dimension or defined as macrometastasis on molecular assay)
4. Fit for axillary treatment and adjuvant therapy
5. Have given written informed consent
Previous inclusion criteria:
Women will be eligible for inclusion only if ALL of the following criteria apply:
1. 18 years or older
2. Unifocal or multifocal invasive tumour with lesion ≤5 cm in its largest dimension, measured pathologically or for women who are randomised intraoperatively
largest tumour diameter on mammogram or ultrasound.
3. No axillary nodal metastasis on clinical and ultrasound examination.
4. At sentinel node biopsy have 1 or 2 sentinel nodes with macrometastases (tumour deposit >2.0mm in largest dimension or defined as macrometastasis on molecular assay)
5. Fit for axillary treatment and adjuvant therapy
6. Have given written informed consent
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
1900
Participant exclusion criteria
Current exclusion criteria as of 14/06/2019:
Women will be excluded if they have:
1. Bilateral invasive breast cancer
2. More than 2 nodes with macrometastases
3. Neoadjuvant therapy for breast cancer except:
3.1. If sentinel node biopsy performed prior to neoadjuvant therapy in women with early breast cancer
3.2. Short duration of neoadjuvant endocrine therapy is acceptable (up to 3 months)
4. Previous axillary surgery on the same body side as the scheduled sentinel node biopsy
5. Not receiving adjuvant systemic therapy
6. Previous cancer less than 5 years previously or concomitant malignancy except:
6.1. Basal or squamous cell carcinoma of the skin or
6.2. In situ carcinoma of the cervix or
6.3. In situ melanoma
6.4. Contra- or ipsilateral in situ breast cancer
Previous exclusion criteria:
Women will be excluded if they have:
1. Bilateral breast cancer
2. More than 2 sentinel node macrometastases or extranodal invasion
3. Neoadjuvant therapy for breast cancer
4. Previous axillary surgery on the same body side as the scheduled sentinel node biopsy
5. Not fit or eligible to receive adjuvant systemic therapy
6. Previous or concomitant malignancy except:
6.1. Adequately treated basal or squamous cell carcinoma of the skin or
6.2. Adequately treated in situ carcinoma of the cervix or
6.3. Adequately treated in situ melanoma
6.4. Contra- or ipsilateral in situ breast cancer
Recruitment start date
01/01/2014
Recruitment end date
31/08/2021
Locations
Countries of recruitment
Australia, New Zealand, United Kingdom
Trial participating centre
Royal Derby Hospital
Derby
DE22 3NE
United Kingdom
Sponsor information
Funders
Funder type
Government
Funder name
National Institute for Health Research (NIHR) (UK)
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Funder name
National Health and Medical Research Council
Alternative name(s)
NHMRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
Australia
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date
Intention to publish date
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list