Condition category
Cancer
Date applied
25/02/2014
Date assigned
25/02/2014
Last edited
17/06/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

31/12/2023

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

Organisation

University Hospitals of Derby and Burton NHS Foundation Trust

Sponsor details

Dr Teresa M. Grieve
Assistant Director of Research & Development
Research & Development Department
Royal Derby Hospital
Derby
DE22 3DT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

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

Federal/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

Publication citations

Additional files

Editorial Notes

17/06/2019: Publication and dissemination plan and IPD sharing statement added. 14/06/2019: The following changes were made to the trial record: 1. Contact details, hypothesis, participant information sheet, interventions, inclusion/exclusion criteria were updated. 2. The recruitment end date was changed from 31/12/2023 to 31/08/2021. 3. Australia and New Zealand were added to the countries of recruitment. 4. The sponsor name was changed from "Derby Hospital NHS Foundation Trust" to "University Hospitals of Derby and Burton NHS Foundation Trust". 5. National Health and Medical Research Council (Australia) was added as a funder.