Condition category
Cancer
Date applied
11/08/2016
Date assigned
11/11/2016
Last edited
18/10/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Breast cancer is a common in older women, affecting 13,000 women in the UK over the age of 70 every year. Despite this, little has been done to study breast cancer in older women to find out the best way to treat this disease and what types of treatment older women prefer. For many older women, treatment is identical to that of younger women as they have comparable levels of health and fitness. Surgery followed by a range of treatments are recommended and often tolerated well. However, for some older women, treatment may need to be changed to take into account other illnesses and frailty which may limit their ability to tolerate the full range of treatments. The problem is that there is little guidance available on this level of age, ill health and frailty, which makes the risks of some treatments (such as surgery and chemotherapy) outweigh the benefits. At present, these decisions are based on the personal expertise of the treating team with no research to guide them to best practice. This has resulted in a high level of variation in practice in the UK. This study hopes to fill this gap in our knowledge by studying UK practice and treatment in older women.

Who can participate?
Women aged over 70 with breast cancer

What the study involves?
The study involves collecting detailed data about how fit older women are at the start of their treatment (other illnesses, level of independence, and quality of life), how they respond to their recommended treatment, and finally, how well their cancer is controlled in the long term. This study has a minimal impact on them, and involves completing some questionnaires (some of which are optional). Women can take part in one of the following three ways. In its simplest form, the study only requires the participants’ permission to collect data about them, with no requirement to complete any questionnaires. The research staff just need permission to access the notes to obtain as much data as they can or ask carers for information if they have cognitive decline. Some women may be happy to spend a little time going through some initial questions about their health, fitness and independence on their first visit, but may not wish to fill in any further detailed quality of life questionnaires at follow-up visits. Some women may be happy to also fill in quality of life questionnaires at their first visit and when they attend follow-up visits.

What are the possible benefits and risks of participating?
This study will not directly benefit participants, but will give a much better understanding of the best ways to treat breast cancer in older women, and also help clinicians themselves to make better choices about treatment. The study is very low risk and involves no change of treatment. The study is designed to pose a minimal burden to participants, meaning that many parts are either optional or can be done later via telephone or postal return of quality of life questionnaires.

Where is the study run from?
Doncaster and Bassetlaw Hospitals NHS Foundation Trust and 48 other trusts in the UK

When is the study starting and how long is it expected to run for?
July 2012 to October 2017

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Ms Charlene Martin

Trial website

https://www.sheffield.ac.uk/oncology-metabolism/research/units/surgicaloncology/research/agegap

Contact information

Type

Public

Primary contact

Ms Charlene Martin

ORCID ID

Contact details

EU27
Department of Oncology and Metabolism
University of Sheffield Medical School
Beech Hill Road
Sheffield
S10 2RX
United Kingdom

Additional identifiers

EudraCT number

2016-000779-25

ClinicalTrials.gov number

Protocol/serial number

DBH 0530/2013/NCT

Study information

Scientific title

Bridging the age gap in breast cancer: improving outcomes for older women

Acronym

Study hypothesis

The Age Gap study will use state of the art statistical and modelling techniques to determine the age, comorbidity, frailty and disease characteristics of women over 70 with early breast cancer to provide guidance on two primary questions:
1. What are the personal and cancer characteristics of women who can be safely advised that surgery is unlikely to confer any advantage for them?
2. What are the personal and cancer characteristics of women who should be advised to have adjuvant chemotherapy after surgery?
These data will be used to provide guidelines for clinicians to ensure that optimal individually tailored treatment is offered to all older women with breast cancer.

Ethics approval

London South East Research Ethics Committee, 30/11/2012 (revised 25/01/2013), ref: 12/LO/1808

Study design

Observational cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

https://www.sheffield.ac.uk/polopoly_fs/1.597185!/file/Patient_Information_Sheet_Version_5_9th_March_2016.docx

Condition

Breast cancer

Intervention

The first phase is to construct a preliminary disease outcome and health economic model of breast cancer in older women. This will be based on the rather limited published trial evidence in this age group and also retrospective data from the UK cancer registry and hospital episode statistics (HES data).

Once the participant has consented, the treatment they have decided to have will just proceed as normal, with no change. Information about how the participant is doing and the treatment they are receiving will be recorded by a member of study staff but the participant's hospital visit will not differ from normal with the exception of going through some questionnaires with a member of the study team about their health, fitness and independence. Health and fitness data will be collected using well validated tools widely used in the field of geriatric research (the IADL, ADL, MMSE, Charlson score etc). These questionnaires are only completed at the baseline visit and if the woman wishes, she may complete these at a later date via a telephone call to minimise the burden of the study at each visit. It is estimated that these baseline questionnaires will take 20 to 30 minutes.

The participant can opt to also take part in answering questionnaires about how they are feeling (quality of life validated questionnaires: the EORTC QLQ C30, BR23 and ELD 15) at baseline and when they attend for their follow up visits. These are all well validated, widely used instruments in health research and are easy to understand and administer. The participant can see the questionnaires before they decide whether they want to take part so they can see what sort of questions they are. If the participant agrees to this option, these questionnaires will be completed pre-treatment and at various follow-up visits. Again, these may be completed later either by the patient themselves (and posted back to the study centre) or via a telephone call.

The participant can also opt to agree to let the study team have potential future access to any biopsy samples of their breast cancer that may have already been taken as part of their normal care. No additional biopsies for the study will be taken. These samples will not be accessed as part of the present study but the consents may be used as the basis for a follow on biological markers study which will be the subject of further funding and ethics applications.

The participant also has the option of agreeing to let the research team follow their long-term progress, even after the clinic has discharged them by giving consent for the study team to have access to their cancer registry and HES data. Follow up by this means would be undertaken for 10 years.

The participant will be seen in the clinic 6 weeks after they started their treatment and then every 6 months after they entered the study for a minimum of 2 years and up to 5 years. At each visit their doctor will perform a routine physical examination to check that their disease is under control and that they are well, the participant will also be asked if they have had any treatment-related problems. If the participant has agreed to full participation, at some of these visits the participant will also be asked by their doctor/nurse to complete some questionnaires about their quality of life. Patients may complete these questionnaires at home after their clinic visit if they wish.

At follow-up visits, patients on Primary Endocrine Therapy will have the size of the primary tumour and the largest of the diseased axillary lymph nodes (if present) measured by the Consultant Breast Surgeon, Consultant Oncologist or an appropriate delegated individual. These assessments are all part of normal routine practice.

At follow-up visits all patients will have the following documented:
1. Treatment details will be recorded e.g. radiotherapy, surgery, chemotherapy, trastuzumab, endocrine therapy
2. Treatment-related adverse events
3. Management of local/regional recurrence, progressive disease, metastatic disease or new primary breast tumour (if applicable)

The data from the cohort study will then be used to modify and improve the preliminary model of cancer outcomes and enable us to develop two management algorithms for older women with breast cancer. These will be made freely available as web-based tools to help to guide clinicians in optimising the management of older women.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Global health status/quality of life, measured using questions 29+30 of The European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30) at 6 weeks and 6 months post-intervention

Secondary outcome measures

Measured at the time of diagnosis:
1. Comorbidity, measured using the Charlson comorbidity index
2. Frailty, measured using the Barthel Index (ADL) and instrumental activities of daily living scores (IADL)
3. Cognitive status, measured using the mini-mental state examination MMSE)
4. Quality of life, measured using the EORTC QLQ C30, EORTC breast cancer-specific quality-of-life questionnaire (BR23), EORTC quality of life questionnaire module for older people with cancer (EORTC ELD 15, EuroQol Group EQ-5D)
4. Tumour stage, grade and receptor status

Overall trial start date

01/07/2012

Overall trial end date

21/10/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Female
2. Aged over 70 years of age at the time of diagnosis of cancer
3. Primary operable (TNM categories: T1 (Tumour 2 cm or less in greatest dimension), T2 (Tumour more than 2 cm but not more than 5 cm in greatest dimension), T3 (Tumour more than 5 cm in greatest dimension), N0 (No regional lymph node metastasis), N1 (Metastasis in movable ipsilateral axillary lymph node(s), M0 (No distant metastasis)) invasive breast cancer (core biopsy or diagnostic incision biopsy)
4. Tumour ER and Her-2 status will be available and categorised according to accepted scoring systems e.g. H score 6 or Allred score 57 for ER and for Her-2, IHC score 1-3 plus FISH testing if IHC equivocal
5. Ability to give informed consent if considering full or partial trial participation (see below)
6. Willing to complete the questionnaires for the additional trial evaluations if considering full trial participation
7. If suitable for data collection only, the patient does not need to give consent but participation in the data collection exercise should be agreed and assented to by their next of kin, friend or carer

Participant type

Patient

Age group

Senior

Gender

Female

Target number of participants

3000

Participant exclusion criteria

1. Disease unsuitable for surgery e.g. inoperable or metastatic disease
2. Previous invasive breast cancer (within past 5 years)
3. There is no restriction for people who are unable to speak English. Translation of study documents and translators will be undertaken by recruiting centres if required
4. For patients considered for the PET versus surgery comparison, use of concurrent Hormone Replacement Therapy (HRT) or therapy with any other oestrogen-containing preparation is an exclusion criteria, unless treatment is discontinued for 4 weeks before the study starts
5. There is no restriction for any co-morbidity or frailty as the study aims to capture data on management and outcomes in these cases
6. Patient without capacity being considered for the data collection only arm of the study but for whom there is no consultee available

Recruitment start date

01/04/2013

Recruitment end date

31/08/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Doncaster and Bassetlaw Hospitals NHS Trust
Doncaster Royal Infirmary
Doncaster
DN2 5LT
United Kingdom

Trial participating centre

Sheffield Teaching Hospitals
Royal Hallamshire Hospital
Sheffield
S10 2JF
United Kingdom

Trial participating centre

Barnsley Hospital NHS Trust
Barnsley Hospital
Barnsley
S75 2EP
United Kingdom

Trial participating centre

Milton Keynes Hospital NHS Trust
Milton Keynes Hospital
Milton Keynes
MK6 5LD
United Kingdom

Trial participating centre

North Lincolnshire & Goole NHS Trust
Diana, Princess of Wales Hospital Scunthorpe General Hospital
DN33 2BA
United Kingdom

Trial participating centre

University Hospitals of Leicester
Glenfield Hospital Leicester Royal Infirmary
Leicester
LE1 5WW
United Kingdom

Trial participating centre

East Lancashire Teaching Hospitals
Burnley General Hospital
Burnley
BB10 2PQ
United Kingdom

Trial participating centre

Harrogate & District Foundation Trust
Harrogate District Hospital
Harrogate
HG2 7SX
United Kingdom

Trial participating centre

St Helens & Knowsley Teaching Hospitals NHS Trust
Whiston Hospital
Prescot
L35 5DR
United Kingdom

Trial participating centre

York Teaching Hospital NHS Foundation Trust
The York Hospital Scarborough Hospital
York
YO31 8HE
United Kingdom

Trial participating centre

Royal Liverpool and Broadgreen University Hospitals NHS Trust
Royal Liverpool University Hospital
Liverpool
L7 8XP
United Kingdom

Trial participating centre

Airedale NHS Foundation Trust
Airedale General Hospital
Keighley
BD20 6TD
United Kingdom

Trial participating centre

Leeds Teaching Hospitals NHS Trust
St James's University Hospital
Leeds
LS9 7TF
United Kingdom

Trial participating centre

Bradford Teaching Hospitals NHS Trust
St Luke's Hospital
Bradford
BD5 0NA
United Kingdom

Trial participating centre

Cardiff and Vale University Health Board
University Hospital Llandough
Llandough
CF64 2XX
United Kingdom

Trial participating centre

Aneurin Bevan Health Board
Royal Gwent Hospital, Newport Nevill Hall Hospital, Abergavenny
Newport
NP18 3XQ
United Kingdom

Trial participating centre

University Hospitals of Morecambe Bay NHS Trust
Royal Lancaster Infirmary Furness General Hospital
Lancaster
LA1 4RP
United Kingdom

Trial participating centre

University Hospitals Coventry & Warwickshire NHS Trust
University Hospital
Coventry
CV2 2DX
United Kingdom

Trial participating centre

United Lincolnshire Hospitals NHS Trust
Lincoln County Hospital Grantham and District Hospital Pilgrim Hospital Boston
Lincolnshire
LN2 5QY
United Kingdom

Trial participating centre

Hull and East Yorkshire Hospitals NHS Trust
Castle Hill Hospital
Hull
HU16 5JQ
United Kingdom

Trial participating centre

Nottingham University Hospitals NHS Trust
Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Southport & Ormskirk Hospital NHS Trust
Southport & Formby District General Hospital
Southport
PR8 6PN
United Kingdom

Trial participating centre

Mid Cheshire Hospitals NHS Foundation Trust
Leighton Hospital
Crewe
CW1 4QJ
United Kingdom

Trial participating centre

Royal Marsden NHS Foundation Trust
The Royal Marsden, Chelsea, London The Royal Marsden, Sutton Surrey
London
SW3 6JJ
United Kingdom

Trial participating centre

Gloucestershire Hospitals NHS Trust
Gloucestershire Royal Hospital Cheltenham General Hospital
Gloucester
GL1 3NN
United Kingdom

Trial participating centre

Guys and St Thomas' NHS Foundation Trust
Guy's Hospital
London
SE1 9RT
United Kingdom

Trial participating centre

Dorset County Hospitals NHS Foundation Trust
Dorset County Hospital
Dorchester
DT1 2JY
United Kingdom

Trial participating centre

Mid Essex Hospital Services Trust
Broomfield Hospital
Chelmsford
CM1 7ET
United Kingdom

Trial participating centre

Mid Yorkshire Hospitals NHS Trust
Pinderfields General Hospital
Wakefield
WF1 4DG
United Kingdom

Trial participating centre

North Bristol NHS Trust
Southmead Hospital
Bristol
BS10 5NB
United Kingdom

Trial participating centre

Chesterfield Royal Hospital NHS Foundation Trust
Chesterfield Hospital
Chesterfield
S44 5BL
United Kingdom

Trial participating centre

Rotherham NHS Foundation Trust
Rotherham General Hospital
Rotherham
S60 2UD
United Kingdom

Trial participating centre

Dartford and Gravesham Trust
Darent Valley Hospital
Dartford
DA2 8DA
United Kingdom

Trial participating centre

Kingston Hospital NHS Foundation Trust
Kingston Hospital
Kingston upon Thames
KT2 7QB
United Kingdom

Trial participating centre

Colchester Hospital University NHS Foundation Trust
Essex County Hospital
Colchester
CO3 3NB
United Kingdom

Trial participating centre

Yeovil District Hospital Foundation Trust
Yeovil District Hospital
Yeovil
BA21 4AT
United Kingdom

Trial participating centre

Croydon Health Services NHS Trust
Croydon University Hospital
Croydon
CR9 2RS
United Kingdom

Trial participating centre

North Tees and Hartlepool NHS Trust
University Hospital of North Tees
Stockton on Tees
TS19 8PE
United Kingdom

Trial participating centre

South Tees NHS Foundation Trust
The James Cook University Hospital
Middlesbrough
TS4 3BW
United Kingdom

Trial participating centre

Luton and Dunstable University Hospital NHS Foundation Trust
Luton and Dunstable Hospital
Luton
LU4 0DZ
United Kingdom

Trial participating centre

Weston Area Health NHS Trust
Weston General Hospital
Weston-super-Mare
BS23 4TQ
United Kingdom

Trial participating centre

Tameside Hospital NHS Foundation Trust
Tameside General Hospital
Ashton-under-Lyne
OL6 9RW
United Kingdom

Trial participating centre

East Cheshire NHS Trust
Macclesfield District General Hospital
Macclesfield
SK10 3BL
United Kingdom

Trial participating centre

Wrightington, Wigan and Leigh NHS Trust
Royal Albert Edward Infirmary
Wigan
WN1 2NN
United Kingdom

Trial participating centre

Sherwood Forest Hospitals NHS Foundation Trust
King's Mill Hospital
Sutton-in-Ashfield
NG17 4JL
United Kingdom

Trial participating centre

University Hospital of South Manchester NHS Foundation Trust
Wythenshawe Hospital
Manchester
M23 9LT
United Kingdom

Trial participating centre

Aintree University Hospital NHS Foundation Trust
Aintree University Hospital
Liverpool
L9 7AL
United Kingdom

Trial participating centre

Sandwell and West Birmingham Hospitals NHS Foundation Trust
Birmingham City Hospital
Birmingham
B18 7QH
United Kingdom

Trial participating centre

Brighton and Sussex University Hospitals NHS Foundation Trust
The Park Centre for Breast Care
Brighton
BN1 6AG
United Kingdom

Sponsor information

Organisation

Doncaster and Bassetlaw Hospitals NHS Foundation Trust

Sponsor details

R&D Office
C Block
Doncaster Royal Infirmary
Armthorpe Road
Doncaster
DN2 5LT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

IPD sharing plan
The datasets generated and/or analysed during the current study are available from Ms Lynda Wyld (l.wyld@sheffield.ac.uk) on reasonable request.

Intention to publish date

21/10/2018

Participant level data

Available on request

Results - basic reporting

Publication summary

2015 results in: https://www.ncbi.nlm.nih.gov/pubmed/26108734
2015 results in: http://www.ejso.com/article/S0748-7983(15)00112-2/abstract
2015 results in: https://www.ncbi.nlm.nih.gov/pubmed/26043439
2015 results in: https://www.ncbi.nlm.nih.gov/pubmed/26058557
2015 results in: https://www.ncbi.nlm.nih.gov/pubmed/25534045

Publication citations

Additional files

Editorial Notes

18/10/2017: Internal review.