Neoadjuvant trial of pre-operative exemestane or letrozole +/- celecoxib in the treatment of oestrogen receptor-positive early breast cancer
| ISRCTN | ISRCTN09768535 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN09768535 |
| Secondary identifying numbers | BR3031 |
- Submission date
- 02/06/2006
- Registration date
- 11/07/2006
- Last edited
- 15/09/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Ms Claire Gaunt
Scientific
Scientific
Cancer Research UK Clinical Trials Unit (CRCTU)
School of Cancer Sciences
University of Birmingham
Birmingham
B15 2TT
United Kingdom
| Phone | +44 (0)121 4143797 |
|---|---|
| neoexcel@trials.bham.ac.uk |
Dr Phillippa Treharne-Jones
Scientific
Scientific
Cancer Research UK (CR UK) Clinical Trials Unit
Institute of Cancer and Genomic Sciences
The University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
| Phone | +44 (0)121 414 3797 |
|---|---|
| neoexcel@trials.bham.ac.uk |
Study information
| Study design | Prospective phase III multicentre bifactorial (four-arm) randomised clinical trial with both open-label and placebo-controlled comparisons |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Neoadjuvant trial of pre-operative exemestane or letrozole +/- celecoxib in the treatment of oestrogen receptor-positive early breast cancer |
| Study acronym | NEO-EXCEL |
| Study objectives | The hypotheses to be addressed in this bifactoral phase III trial are that exemestane may be superior to letrozole (the present standard of care), as primary neoadjuvant endocrine therapy for early stage oestrogen receptor (ER)-positive breast cancer in postmenopausal women, and that the activity of aromatase inhibitors in this setting may significantly be enhanced by the addition of the selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib. |
| Ethics approval(s) | West Midlands MREC, 21/07/2006, ref: 06/MRE07/31 |
| Health condition(s) or problem(s) studied | Early breast cancer |
| Intervention | Subjects will be randomised (1:1:1:1) to receive either: 1. Exemestane + celecoxib (these patients will receive exemestane 25 mg, one tablet daily and celecoxib 400 mg, one tablet twice daily) 2. Exemestane + celecoxib-placebo (these patients will receive exemestane 25 mg, one tablet daily and celecoxib-placebo, one tablet twice daily) 3. Letrozole + celecoxib (these patients will receive letrozole 2.5 mg, one tablet daily and celecoxib 400 mg, one tablet twice daily) 4. Letrozole + celecoxib-placebo (these patients will receive letrozole 2.5 mg, one tablet daily and celecoxib-placebo, one tablet twice daily) Treatment will continue for 16 weeks until day of surgery. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Exemestane, letrozole, celecoxib |
| Primary outcome measure | Objective clinical response (complete response [CR], partial response [PR]) to neoadjuvant treatment |
| Secondary outcome measures | 1. Objective ultrasound-determined response (CR, PR) to neoadjuvant treatment 2. Type of surgery 3. Axillary lymph node involvement at surgery 4. Complete pathological response 5. Local recurrence-free survival 6. Progression-free survival 7. Overall survival For translational sub-study: biological profiling for prognostic and predictive indicators |
| Overall study start date | 01/08/2007 |
| Completion date | 01/04/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target number of participants | 266 |
| Total final enrolment | 269 |
| Key inclusion criteria | 1. Biopsy proven 2. ER positive invasive breast cancer (where ER positive is defined as equivalent to an ER Quick or Allred score of 3 or greater) 3. Tumour, measured on clinical examination, as greater than 2 cm in diameter 4. Postmenopausal 5. Adequate haematological, renal and liver function, defined as: platelets of greater than 100 x 10(9)/l, white blood cell count of greater than 3 x 10(9)/l, creatinine less than 110 mmol/l, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) less than 1.25 x upper limit of normal 6. Patients must be fit to complete surgery for their breast cancer 7. Written informed consent 8. Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2 |
| Key exclusion criteria | 1. Bilateral breast cancer 2. Evidence of distant metastases (M1) 3. Patients who have received previous treatment for breast cancer 4. Concomitant active malignancy except for adequately treated carcinoma in situ of the uterine cervix or basal cell carcinoma of the skin 5. Co-morbid disease which would preclude safe surgical treatment of the primary cancer 6. Other physical or psychiatric disorder that may interfere with subject compliance, adequate informed consent or determine the causality of adverse events 7. Contraindications to celecoxib: active peptic ulcer disease, renal impairment, asthma exacerbated by non steroidal anti-inflammatory drugs (NSAIDs), congestive cardiac failure (New York Heart Association [NYHA II-IV]), ischaemic heart disease, cerebrovascular disease, uncontrolled hypertension 8. Patients with an ongoing requirement for regular NSAID or COX-2 inhibitor therapy (asprin 75 mg daily is permitted) 9. Regular selective COX-2 inhibitor use in the two years prior to randomisation 10. History of hypersensitivity to celecoxib, exemestane or letrozole or to any of the excipients 11. Known hypersensitivity to sulphonamides 12. Patients who have experienced asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid or NSAIDs including COX-2 inhibitors 13. Inflammatory bowel disease 14. Patients with ongoing requirements for fluconazole or ketoconazole therapy 15. Patients with ongoing requirement for lithium therapy 16. Patients with ongoing requirement for angiotensin-converting enzyme (ACE) inhibitor therapy 17. Patients who are anticoagulated |
| Date of first enrolment | 07/08/2007 |
| Date of final enrolment | 29/04/2014 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
Barnet Hospital
Barnet
EN5 3DJ
United Kingdom
EN5 3DJ
United Kingdom
Broomfield Hospital
CM1 7ET
United Kingdom
United Kingdom
Chelmsford and Essex Centre
CM2 0QH
United Kingdom
United Kingdom
Cheltenham General Hospital
GL53 7AN
United Kingdom
United Kingdom
City Hospital
B18 7QH
United Kingdom
United Kingdom
Essex County Hospital
CO3 3NB
United Kingdom
United Kingdom
Forth Valley Royal Hospital
FK5 4WR
United Kingdom
United Kingdom
Frenchay Hospital
BS16 1QR
United Kingdom
United Kingdom
Frimley Park Hospital
GU16 7UJ
United Kingdom
United Kingdom
Good Hope Hospital
B75 7RR
United Kingdom
United Kingdom
Grantham and District Hospital
NG31 8DG
United Kingdom
United Kingdom
Leeds General Infirmary
LS1 3EX
United Kingdom
United Kingdom
Peterborough City Hospital
PE3 9GZ
United Kingdom
United Kingdom
Princess Royal University Hospital
TF1 6TF
United Kingdom
United Kingdom
Royal United Hospital
BA1 3NG
United Kingdom
United Kingdom
Southport and Formby District General Hospital
PR8 6PN
United Kingdom
United Kingdom
St James's University Hospital
LS9 7TF
United Kingdom
United Kingdom
St Margaret's Hospital
CM16 6TN
United Kingdom
United Kingdom
The Queen Elizabeth Hospital
B15 2TH
United Kingdom
United Kingdom
University Hospital
CV2 2DX
United Kingdom
United Kingdom
Wishaw General Hospital
ML2 0DP
United Kingdom
United Kingdom
Wythenshawe Hospital
M23 9LT
United Kingdom
United Kingdom
Sponsor information
University Hospital Birmingham NHS Foundation Trust (UK)
University/education
University/education
c/o University of Birmingham
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/014ja3n03 |
|---|
Funders
Funder type
Industry
Cancer Research UK
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Pfizer UK - educational grant
Private sector organisation / For-profit companies (industry)
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Pfizer Ltd, Pfizer Limited
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/07/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | Current publication and dissemination plan as of 01/03/2022: Planned publication in a high-impact peer-reviewed journal in approximately July 2022 Previous publication and dissemination plan: Planned publication in a high-impact peer-reviewed journal in approximately November 2017 |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be included in the subsequent results publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Abstract results | 15/02/2016 | 02/03/2022 | No | No | |
| Plain English results | 15/09/2022 | No | Yes |
Editorial Notes
02/09/2022: Cancer Research UK plain English results link added.
02/03/2022: Abstract added.
01/03/2022: The publication and dissemination plan was updated and the intention to publish date was changed from 31/03/2022 to 31/07/2022.
18/05/2021: The following changes were made to the trial record:
1. The total final enrolment was added.
2. The intention to publish date was changed from 31/03/2021 to 31/03/2022.
18/09/2020: The intention to publish date has been changed from 01/11/2017 to 31/03/2021.
23/05/2017: Trial participating centres added to trial record.
19/05/2017: The overall trial date was changed from 01/05/2012 to 01/04/2019.
15/02/2011: The overall trial end date was changed from 01/08/2010 to 01/05/2012 and the target number of participants was changed from 1000 to 256.
14/05/2008: The overall trial start date was changed from 01/08/2006 to 01/08/2007.
