Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Ms Claire Gaunt
ORCID ID
Contact details
Cancer Research UK Clinical Trials Unit (CRCTU)
School of Cancer Sciences
University of Birmingham
Birmingham
B15 2TT
United Kingdom
+44 (0)121 4143797
neoexcel@trials.bham.ac.uk
Type
Scientific
Additional contact
Dr Phillippa Treharne-Jones
ORCID ID
Contact details
Cancer Research UK (CR UK) Clinical Trials Unit
Institute of Cancer and Genomic Sciences
The University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 (0)121 414 3797
neoexcel@trials.bham.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
BR3031
Study information
Scientific title
Neoadjuvant trial of pre-operative exemestane or letrozole +/- celecoxib in the treatment of oestrogen receptor-positive early breast cancer
Acronym
NEO-EXCEL
Study hypothesis
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
West Midlands MREC, 21/07/2006, ref: 06/MRE07/31
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
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
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 names
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 trial start date
01/08/2007
Overall trial end date
01/04/2019
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
266
Participant 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
Recruitment start date
07/08/2007
Recruitment end date
29/04/2014
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Barnet Hospital
EN5 3DJ
Trial participating centre
Broomfield Hospital
CM1 7ET
Trial participating centre
Chelmsford and Essex Centre
CM2 0QH
Trial participating centre
Cheltenham General Hospital
GL53 7AN
Trial participating centre
City Hospital
B18 7QH
Trial participating centre
Essex County Hospital
CO3 3NB
Trial participating centre
Forth Valley Royal Hospital
FK5 4WR
Trial participating centre
Frenchay Hospital
BS16 1QR
Trial participating centre
Frimley Park Hospital
GU16 7UJ
Trial participating centre
Good Hope Hospital
B75 7RR
Trial participating centre
Grantham and District Hospital
NG31 8DG
Trial participating centre
Leeds General Infirmary
LS1 3EX
Trial participating centre
Peterborough City Hospital
PE3 9GZ
Trial participating centre
Princess Royal University Hospital
TF1 6TF
Trial participating centre
Royal United Hospital
BA1 3NG
Trial participating centre
Southport and Formby District General Hospital
PR8 6PN
Trial participating centre
St James's University Hospital
LS9 7TF
Trial participating centre
St Margaret's Hospital
CM16 6TN
Trial participating centre
The Queen Elizabeth Hospital
B15 2TH
Trial participating centre
University Hospital
CV2 2DX
Trial participating centre
Wishaw General Hospital
ML2 0DP
Trial participating centre
Wythenshawe Hospital
M23 9LT
Funders
Funder type
Industry
Funder name
Cancer Research UK
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Funder name
Pfizer UK - educational grant
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal in approximately November 2017.
IPD sharing statement
The datasets generated and/or analysed during the current study will be included in the subsequent results publication.
Intention to publish date
01/11/2017
Participant level data
Other
Basic results (scientific)
Publication list