Clinical trial NCT02338310: Trial of Perioperative Endocrine Therapy - Individualising Care
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
First posted: 2015-01-14
Enrollment: 4486
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine whether perioperative endocrine therapy with an aromatase inhibitor (AI) followed by standard adjuvant therapy improves outcome compared with standard adjuvant therapy alone in postmenopausal women with hormone receptor positive breast cancer.

To determine whether the proliferation marker Ki67 as measured by immunohistochemistry (IHC) in the excised cancer around 2 weeks after starting AI therapy will predict for time to recurrence (TTR) in the individual patient more effectively than the pre-treatment Ki67 value.

To determine whether molecular profiling 2 weeks after starting endocrine therapy predicts for long-term outcome in postmenopausal women with hormone receptor positive breast cancer better than at diagnosis.


Eligibility criteria: Inclusion Criteria:

1. Post menopausal women with core biopsy-proven hormone receptor positive invasive breast cancer. Postmenopausal is defined as a woman aged ≥50 years fulfilling any one of the following criteria:

   i) with amenorrhoea \>12 months and an intact uterus; ii) has undergone a bilateral oophorectomy; iii) in women who have undergone a hysterectomy, then FSH levels within the postmenopausal range (utilising ranges from the testing laboratory facility) are required if the patient is aged \<55 years; or iv) in women who have been on HRT within the last 12 months and therefore not amenorrhoeic, FSH levels within the postmenopausal range (utilising ranges from the testing laboratory facility) are required if the patient is aged \<55 years.
2. No evidence of metastatic spread by standard assessment according to local guidelines
3. Standard adjuvant endocrine therapy indicated
4. A palpable tumour of any size , or a tumour with an ultrasound size of at least 1.5cm
5. WHO performance status of 0 or 1
6. Written informed consent to participate in the trial and to donation of tissue (fresh tissue and surplus tissue from diagnostic procedures) and blood samples.

Exclusion Criteria:

1. Locally advanced/inoperable breast cancer
2. Evidence of metastatic disease
3. Previous invasive breast cancer (surgically treated DCIS or LCIS allowed)
4. Current bilateral breast cancer
5. Multiple unilateral tumours with different ER/PgR/HER2 status, grade or type (e.g. ductal vs lobular) i.e. anything that suggests two or more different cancers. Multifocal disease with homogenous ER/PgR/HER2 status, grade and type is allowed if at least one lesion is palpable or at least 1.5cm on ultrasound; the largest lesion should be used for sample collection and CRF completion.
6. Concurrent use (defined as use within 4 weeks prior to diagnostic tissue sample being taken) of HRT or any other oestrogen-containing medication (including vaginal oestrogens)
7. Previous use of oestrogen implants at ANY time
8. Prior endocrine therapy or chemotherapy for breast cancer
9. Any invasive malignancy diagnosed within previous 5 years (other than basal cell carcinoma or cervical carcinoma in situ)
10. Any severe co-incident medical disease, inability to give informed consent or unavailability for follow-up
11. Treatment with an unlicensed or investigational drug within 4 weeks before randomisation
12. Current, continuous, long term systemic steroid usage

Primary outcomes:
measure: Time to recurrence
timeFrame: 5 years post-randomisation
Secondary outcomes:
measure: Relapse free survival
timeFrame: 5 years post-randomisation
measure: Time to local recurrence
timeFrame: 5 years post-randomisation
measure: Time to distant recurrence
timeFrame: 5 years post-randomisation
measure: Overall Survival
timeFrame: 5 years post-randomisation
measure: Breast cancer free survival
timeFrame: 5 years post-randomisation
measure: Proliferation rate (Ki67)
timeFrame: At time of surgery (around 2 weeks post-randomisation)
measure: Gene expression profile
timeFrame: At time of surgery (around 2 weeks post-randomisation)
Other outcomes:
Locations:
city: Dundonald
country: United Kingdom
facility: Ulster Hospital
state: Belfast
city: Slough
country: United Kingdom
facility: Heatherwood and Wexham Park Hospitals NHS trust
state: Berkshire
city: Aylesbury
country: United Kingdom
facility: Stoke Mandeville Hospital
state: Buckinghamshire
city: Llanelli
country: United Kingdom
facility: Prince Philip Hospital
state: Carmarthenshire
city: Portadown
country: United Kingdom
facility: Craigavon Area Hospital
state: Co.Amagh
city: Ashington
country: United Kingdom
facility: Wansbeck General Hospital
state: England
city: Barnstaple
country: United Kingdom
facility: North Devon District Hospital
state: England
city: Birmingham
country: United Kingdom
facility: City Hospital - Birmingham
state: England
city: Blackburn
country: United Kingdom
facility: Royal Blackburn Hospital
state: England
city: Boston
country: United Kingdom
facility: Pilgrim Hospital
state: England
city: Bradford
country: United Kingdom
facility: Bradford Teaching Hospitals NHS Trust, St Luke's Hospital
state: England
city: Burnley
country: United Kingdom
facility: Burnley General Hospital
state: England
city: Carlisle
country: United Kingdom
facility: Cumberland Infirmary
state: England
city: Chelmsford
country: United Kingdom
facility: Chelmsford and Essex Centre
state: England
city: Chesterfield
country: United Kingdom
facility: Chesterfield Royal Hospital
state: England
city: Chester
country: United Kingdom
facility: Countess of Chester Hospital
state: England
city: Colchester
country: United Kingdom
facility: Essex County Hospital
state: England
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary
state: England
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
state: England
city: High Wycombe
country: United Kingdom
facility: Wycombe General Hospital
state: England
city: Keighley
country: United Kingdom
facility: Airedale General Hospital
state: England
city: Kidderminster
country: United Kingdom
facility: Kidderminster Hospital
state: England
city: London
country: United Kingdom
facility: Whittington Hospital
state: England
city: London
country: United Kingdom
facility: Royal Free Hospital
state: England
city: London
country: United Kingdom
facility: Guy's Hospital
state: England
city: London
country: United Kingdom
facility: King's College Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden - London
state: England
city: London
country: United Kingdom
facility: St. Mary's Hospital
state: England
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
state: England
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital - Penine Actute Hospitals Trust
state: England
city: North Shields
country: United Kingdom
facility: North Tyneside Hospital
state: England
city: Northampton
country: United Kingdom
facility: Northampton General Hospital NHS Trust
state: England
city: Nuneaton
country: United Kingdom
facility: George Eliot Hospital
state: England
city: Oldham
country: United Kingdom
facility: Royal Oldham Hospital
state: England
city: Poole Dorset
country: United Kingdom
facility: Poole Hospital
state: England
city: Reading
country: United Kingdom
facility: Royal Berkshire Hospital
state: England
city: Stoke-On-Trent
country: United Kingdom
facility: University Hospital of North Staffordshire
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden Hosital,
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend NHS Trust Hospital
state: England
city: Winchester
country: United Kingdom
facility: Royal Hampshire County Hospital
state: England
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: England
city: Worcester
country: United Kingdom
facility: Worcester Royal Hospital
state: England
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
state: England
city: Epping
country: United Kingdom
facility: St Margaret's Hospital
state: Essex
city: Gloucester
country: United Kingdom
facility: Cheltenham General Hospital
state: Gloucs
city: St Albans
country: United Kingdom
facility: St Albans City Hospital
state: Hertfordshire
city: Welwyn Garden City
country: United Kingdom
facility: Queen Elizabeth II Hospital
state: Hertfordshire
city: Gillingham
country: United Kingdom
facility: Medway Maritime Hospital
state: Kent
city: Orpington
country: United Kingdom
facility: Princess Royal University Hospital
state: Kent
city: Tunbridge Wells
country: United Kingdom
facility: Tunbridge Wells Hospital
state: Kent
city: Grantham
country: United Kingdom
facility: Grantham and District Hospital
state: Lincolnshire
city: Lewisham
country: United Kingdom
facility: University Hospital, Lewisham
state: London
city: Woolwich
country: United Kingdom
facility: Queen Elizabeth Hospital
state: London
city: Southall
country: United Kingdom
facility: Ealing Hospital
state: Middlesex
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary
state: Newcastle-Upon-Tyne
city: Harrogate
country: United Kingdom
facility: Harrogate District Hospital
state: North Yorkshire
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Dumfries
country: United Kingdom
facility: Dumfries & Galloway Royal Infirmary
state: Scotland
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Scotland
city: Telford
country: United Kingdom
facility: Princess Royal Hospital
state: Shropshire
city: Weston-Super-Mare
country: United Kingdom
facility: Weston General Hospital, Avon
state: Somerset
city: Barnsley
country: United Kingdom
facility: Barnsley District General Hospital
state: South Yorkshire
city: Rotherham
country: United Kingdom
facility: Rotherham District General Hospital
state: South Yorkshire
city: Chertsey
country: United Kingdom
facility: Ashford and St Peter's Hospitals
state: Surrey
city: Kingston Upon Thames
country: United Kingdom
facility: Kingston Hospital
state: Surrey
city: Redhill
country: United Kingdom
facility: East Surrey Hospital
state: Surrey
city: Aberystwyth
country: United Kingdom
facility: Bronglais District General Hospital
state: Wales
city: Haverfordwest
country: United Kingdom
facility: Withybush General Hospital
state: Wales
city: Rhyl
country: United Kingdom
facility: North Wales CTC, Glan Clwyd Hospital
state: Wales
city: Swansea
country: United Kingdom
facility: Singleton Hospital
state: Wales
city: Port Talbot
country: United Kingdom
facility: Neath Port Talbot Hospital
state: West Glamorgan
city: Ashton-Under-Lyne
country: United Kingdom
facility: Tameside General Hospital
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Bolton
country: United Kingdom
facility: Royal Bolton Hospital
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth General Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Canterbury
country: United Kingdom
facility: East Kent Hospitals
city: Cardiff
country: United Kingdom
facility: University Hospital Of Wales
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
city: Coventry
country: United Kingdom
facility: University Hospital Coventry
city: Crewe
country: United Kingdom
facility: Leighton Hospital
city: Dartford
country: United Kingdom
facility: Darent Valley Hospital
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: Frimley
country: United Kingdom
facility: Frimley Park Hospital
city: Glasgow
country: United Kingdom
facility: Western Infirmary
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Hereford
country: United Kingdom
facility: Hereford County Hospital
city: Huddersfield
country: United Kingdom
facility: Huddersfield Royal Infirmary
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary/ St James' University Hospital
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Homerton University Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: London
country: United Kingdom
facility: Northwick Park Hospital
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: Luton
country: United Kingdom
facility: Luton and Dunstable Hospital
city: Macclesfield
country: United Kingdom
facility: Macclesfield District General Hospital
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
city: Middlesex
country: United Kingdom
facility: Hillingdon Hospital
city: Milton Keynes
country: United Kingdom
facility: Milton Keynes General Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Poole
country: United Kingdom
facility: Dorset County Hospital
city: Romford
country: United Kingdom
facility: Queen's Hospital,
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
city: Salisbury
country: United Kingdom
facility: Salisbury District Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Stafford
country: United Kingdom
facility: Staffordshire General Hospital
city: Stockport
country: United Kingdom
facility: Stepping Hill Hospital
city: Stockton-on-Tees
country: United Kingdom
facility: University Hospital of North Tees
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
city: Tooting
country: United Kingdom
facility: St George's Hospital,
city: Torquay
country: United Kingdom
facility: Torbay District General Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
city: Wakefield
country: United Kingdom
facility: Mid Yorkshire Hospitals
city: Warwick
country: United Kingdom
facility: Warwick Hospital
city: Wigan
country: United Kingdom
facility: Royal Albert Edward Infirmary
city: Worthing
country: United Kingdom
facility: Worthing Hospital
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Ian Smith, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Smith I, Robertson J, Kilburn L, Wilcox M, Evans A, Holcombe C, Horgan K, Kirwan C, Mallon E, Sibbering M, Skene A, Vidya R, Cheang M, Banerji J, Morden J, Sidhu K, Dodson A, Bliss JM, Dowsett M. Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early breast cancer (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial. Lancet Oncol. 2020 Nov;21(11):1443-1454. doi: 10.1016/S1470-2045(20)30458-7.