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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT02338310
Other study ID # ICR-CTSU/2007/10015
Secondary ID 2007-003877-21CR
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date September 2008
Est. completion date April 2034

Study information

Verified date February 2020
Source Institute of Cancer Research, United Kingdom
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 4486
Est. completion date April 2034
Est. primary completion date April 2024
Accepts healthy volunteers No
Gender Female
Age group 50 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Aromatase Inhibitors
Choice of AI is according to centre policy; any brand can be used

Locations

Country Name City State
United Kingdom Aberdeen Royal Infirmary Aberdeen Scotland
United Kingdom Bronglais District General Hospital Aberystwyth Wales
United Kingdom Wansbeck General Hospital Ashington England
United Kingdom Tameside General Hospital Ashton-Under-Lyne
United Kingdom Stoke Mandeville Hospital Aylesbury Buckinghamshire
United Kingdom Ysbyty Gwynedd Bangor
United Kingdom Barnsley District General Hospital Barnsley South Yorkshire
United Kingdom North Devon District Hospital Barnstaple England
United Kingdom Royal United Hospital Bath
United Kingdom Belfast City Hospital Belfast Northern Ireland
United Kingdom City Hospital - Birmingham Birmingham England
United Kingdom Queen Elizabeth Hospital Birmingham
United Kingdom Royal Blackburn Hospital Blackburn England
United Kingdom Royal Bolton Hospital Bolton
United Kingdom Pilgrim Hospital Boston England
United Kingdom Royal Bournemouth General Hospital Bournemouth
United Kingdom Bradford Teaching Hospitals NHS Trust, St Luke's Hospital Bradford England
United Kingdom Bristol Royal Infirmary Bristol
United Kingdom Southmead Hospital Bristol
United Kingdom Burnley General Hospital Burnley England
United Kingdom Addenbrooke's Hospital Cambridge
United Kingdom East Kent Hospitals Canterbury
United Kingdom University Hospital Of Wales Cardiff
United Kingdom Cumberland Infirmary Carlisle England
United Kingdom Chelmsford and Essex Centre Chelmsford England
United Kingdom Ashford and St Peter's Hospitals Chertsey Surrey
United Kingdom Countess of Chester Hospital Chester England
United Kingdom Chesterfield Royal Hospital Chesterfield England
United Kingdom Essex County Hospital Colchester England
United Kingdom Castle Hill Hospital Cottingham
United Kingdom University Hospital Coventry Coventry
United Kingdom Leighton Hospital Crewe
United Kingdom Darent Valley Hospital Dartford
United Kingdom Royal Derby Hospital Derby
United Kingdom Doncaster Royal Infirmary Doncaster England
United Kingdom Russells Hall Hospital Dudley England
United Kingdom Dumfries & Galloway Royal Infirmary Dumfries Scotland
United Kingdom Ninewells Hospital Dundee Scotland
United Kingdom Ulster Hospital Dundonald Belfast
United Kingdom St Margaret's Hospital Epping Essex
United Kingdom Royal Devon and Exeter Hospital Exeter
United Kingdom Frimley Park Hospital Frimley
United Kingdom Medway Maritime Hospital Gillingham Kent
United Kingdom Western Infirmary Glasgow
United Kingdom Cheltenham General Hospital Gloucester Gloucs
United Kingdom Grantham and District Hospital Grantham Lincolnshire
United Kingdom Royal Surrey County Hospital Guildford
United Kingdom Harrogate District Hospital Harrogate North Yorkshire
United Kingdom Withybush General Hospital Haverfordwest Wales
United Kingdom Hereford County Hospital Hereford
United Kingdom Wycombe General Hospital High Wycombe England
United Kingdom Huddersfield Royal Infirmary Huddersfield
United Kingdom Ipswich Hospital Ipswich
United Kingdom Airedale General Hospital Keighley England
United Kingdom Kidderminster Hospital Kidderminster England
United Kingdom Kingston Hospital Kingston Upon Thames Surrey
United Kingdom Leeds General Infirmary/ St James' University Hospital Leeds
United Kingdom University Hospitals of Leicester NHS Trust Leicester
United Kingdom University Hospital, Lewisham Lewisham London
United Kingdom Lincoln County Hospital Lincoln
United Kingdom Royal Liverpool University Hospital Liverpool
United Kingdom Prince Philip Hospital Llanelli Carmarthenshire
United Kingdom Charing Cross Hospital London
United Kingdom Guy's Hospital London England
United Kingdom Homerton University Hospital London
United Kingdom King's College Hospital London England
United Kingdom Northwick Park Hospital London
United Kingdom Royal Free Hospital London England
United Kingdom Royal Marsden - London London England
United Kingdom St Bartholomew's Hospital London
United Kingdom St. Mary's Hospital London England
United Kingdom Whittington Hospital London England
United Kingdom Luton and Dunstable Hospital Luton
United Kingdom Macclesfield District General Hospital Macclesfield
United Kingdom Maidstone Hospital Maidstone
United Kingdom North Manchester General Hospital - Penine Actute Hospitals Trust Manchester England
United Kingdom Wythenshawe Hospital Manchester England
United Kingdom Hillingdon Hospital Middlesex
United Kingdom Milton Keynes General Hospital Milton Keynes
United Kingdom Royal Victoria Infirmary Newcastle Newcastle-Upon-Tyne
United Kingdom North Tyneside Hospital North Shields England
United Kingdom Northampton General Hospital NHS Trust Northampton England
United Kingdom Norfolk and Norwich University Hospital Norwich
United Kingdom Nottingham City Hospital Nottingham
United Kingdom George Eliot Hospital Nuneaton England
United Kingdom Royal Oldham Hospital Oldham England
United Kingdom Princess Royal University Hospital Orpington Kent
United Kingdom Derriford Hospital Plymouth
United Kingdom Dorset County Hospital Poole
United Kingdom Poole Hospital Poole Dorset England
United Kingdom Neath Port Talbot Hospital Port Talbot West Glamorgan
United Kingdom Craigavon Area Hospital Portadown Co.Amagh
United Kingdom Royal Berkshire Hospital Reading England
United Kingdom East Surrey Hospital Redhill Surrey
United Kingdom North Wales CTC, Glan Clwyd Hospital Rhyl Wales
United Kingdom Queen's Hospital, Romford
United Kingdom Rotherham District General Hospital Rotherham South Yorkshire
United Kingdom Salford Royal Hospital Salford
United Kingdom Salisbury District Hospital Salisbury
United Kingdom Weston Park Hospital Sheffield
United Kingdom Heatherwood and Wexham Park Hospitals NHS trust Slough Berkshire
United Kingdom Ealing Hospital Southall Middlesex
United Kingdom Southampton General Hospital Southampton
United Kingdom St Albans City Hospital St Albans Hertfordshire
United Kingdom Staffordshire General Hospital Stafford
United Kingdom Stepping Hill Hospital Stockport
United Kingdom University Hospital of North Tees Stockton-on-Tees
United Kingdom University Hospital of North Staffordshire Stoke-On-Trent England
United Kingdom Royal Marsden Hosital, Sutton England
United Kingdom Singleton Hospital Swansea Wales
United Kingdom Musgrove Park Hospital Taunton
United Kingdom Princess Royal Hospital Telford Shropshire
United Kingdom St George's Hospital, Tooting
United Kingdom Torbay District General Hospital Torquay
United Kingdom Royal Cornwall Hospital Truro
United Kingdom Tunbridge Wells Hospital Tunbridge Wells Kent
United Kingdom Mid Yorkshire Hospitals Wakefield
United Kingdom Warwick Hospital Warwick
United Kingdom Queen Elizabeth II Hospital Welwyn Garden City Hertfordshire
United Kingdom Southend NHS Trust Hospital Westcliff-On-Sea England
United Kingdom Weston General Hospital, Avon Weston-Super-Mare Somerset
United Kingdom Royal Albert Edward Infirmary Wigan
United Kingdom Royal Hampshire County Hospital Winchester England
United Kingdom New Cross Hospital Wolverhampton England
United Kingdom Queen Elizabeth Hospital Woolwich London
United Kingdom Worcester Royal Hospital Worcester England
United Kingdom Worthing Hospital Worthing
United Kingdom Yeovil District Hospital Yeovil England

Sponsors (1)

Lead Sponsor Collaborator
Institute of Cancer Research, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Time to recurrence Time to recurrence (TTR) is defined as time from randomisation to local, regional, or distant tumour recurrence or death from breast cancer without prior notification of relapse. Second primary cancers and intercurrent deaths will be treated as censoring events. Patients who are alive and disease free will be censored at the date last seen alive. 5 years post-randomisation
Secondary Relapse free survival Second primary cancers and deaths from non-breast cancer causes in the absence of breast cancer relapse will be treated as censoring events. 5 years post-randomisation
Secondary Time to local recurrence 5 years post-randomisation
Secondary Time to distant recurrence 5 years post-randomisation
Secondary Overall Survival 5 years post-randomisation
Secondary Breast cancer free survival 5 years post-randomisation
Secondary Proliferation rate (Ki67) Comparison of the predictive value of Ki67 at surgery in the perioperative therapy and non perioperative therapy groups will be undertaken using Cox regression, comparing the estimates of the hazard ratios obtained in each treatment group. At time of surgery (around 2 weeks post-randomisation)
Secondary Gene expression profile At time of surgery (around 2 weeks post-randomisation)
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