Condition category
Cancer
Date applied
02/06/2006
Date assigned
11/07/2006
Last edited
23/05/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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 measures

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

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

Sponsor information

Organisation

University Hospital Birmingham NHS Foundation Trust (UK)

Sponsor details

c/o University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Industry

Funder name

Cancer Research UK

Alternative name(s)

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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.