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 |
| Protocol serial number | BR3031 |
| Sponsor | University Hospital Birmingham NHS Foundation Trust (UK) |
| Funders | Cancer Research UK, Pfizer UK - educational grant |
- 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
Plain English summary of protocol
Contact information
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 |
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
| Primary study design | Interventional |
|---|---|
| Study design | Prospective phase III multicentre bifactorial (four-arm) randomised clinical trial with both open-label and placebo-controlled comparisons |
| Secondary study design | Randomised controlled trial |
| Study type | Participant 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 |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Exemestane, letrozole, celecoxib |
| Primary outcome measure(s) |
Objective clinical response (complete response [CR], partial response [PR]) to neoadjuvant treatment |
| Key secondary outcome measure(s) |
1. Objective ultrasound-determined response (CR, PR) to neoadjuvant treatment |
| Completion date | 01/04/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target sample size at registration | 256 |
| 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
- United Kingdom
- England
- Scotland
Study participating centres
EN5 3DJ
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Other |
| 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 | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| 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.
