Neoadjuvant study of Chemotherapy versus EndocriNe Therapy in postmenopausal patients with primary breast cancer

ISRCTN	ISRCTN77234840
DOI	https://doi.org/10.1186/ISRCTN77234840
EudraCT/CTIS number	2006-003596-12
ClinicalTrials.gov number	NCT00963729
Secondary identifying numbers	N/A

Submission date: 31/05/2006
Registration date: 13/07/2006
Last edited: 19/03/2020

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

http://www.cancerhelp.org.uk/trials/a-trial-to-compare-chemotherapy-with-hormone-therapy-before-surgery-for-breast-cancer

Contact information

Prof Charles R Coombes
Scientific

Faculty of Medicine
Imperial College London
Hammersmith Hospitals NHS Trust
8th Floor
MRC Cyclotron Building
Du Cane Road
London
W12 0NN
United Kingdom

Phone	+44 (0)20 8383 5828
Email	c.coombes@imperial.ac.uk

Study information

Study design	Multi-centre randomised parallel-group comparative phase III trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Neoadjuvant study of Chemotherapy versus EndocriNe Therapy in postmenopausal patients with primary breast cancer
Study acronym	Neo-CENT
Study objectives	Neoadjuvant chemotherapy is considered the standard of care in the management of locally advanced breast cancer but phase III trials involving third generation aromatase inhibitors have established both the efficacy of these agents in the neoadjuvant setting. However it is not known whether endocrine therapy is as effective in the neoadjuvant setting as neoadjuvant chemotherapy. There are still many aspects of the pathways of cytoreduction triggered by both chemotherapy and endocrine therapy which are poorly characterized and a study such as this is a valuable opportunity to study these pathways in vivo. In addition, there are currently no reliable biomarkers which will predict for a given patient with estrogen-receptor positive breast cancer whether endocrine or chemotherapy will offer more effective downstaging. If it can be established that endocrine neoadjuvant chemotherapy is as effective as neoadjuvant chemotherapy for estrogen-receptor positive breast cancer, (or more likely a molecular subset thereof), then the result of an in vivo assay of hormone sensitivity in the form of degree of clinical and pathological response may help define a potentially large subset of patients currently receiving adjuvant chemotherapy without survival benefit. Please note as of 08/02/2011 the overall trial end date has been extended from 31/12/2008 to 31/03/2011 and the target number of participants increased from 644 to 716.
Ethics approval(s)	Leeds (East) Research Ethics Committee on 23/01/2008 (ref: 07/H1306/164).
Health condition(s) or problem(s) studied	Breast Cancer
Intervention	Arm A: fluorouracil (5 FU) 600 mg/m2, epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2; six cycles every 21 days Arm B: letrozole 2.5 mg po per day for 21 weeks
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Epirubicin, cyclophosphamide, fluorouracil and letrozole
Primary outcome measure	1. Clinical response rates
Secondary outcome measures	1. Radiological response rates using breast ultrasound and mammogram 2. To compare the rates of conservation surgery 3. To compare degree of pathological response 4. To compare Ki-67 protein changes and its relationship to treatment response 5. To investigate the roles of members of the forkhead family in mediating endocrine and chemotherapy-induced regression 6. To evaluate the length of time to maximum response within the treatment period 7. To compare effects on markers of apoptosis and the cell cycle 8. To compare tolerability of the various treatments 9. To compare quality of life (QoL) of the various treatments
Overall study start date	01/09/2006
Completion date	31/03/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target number of participants	40 for feasibility study and 676 for main study (716 total)
Key inclusion criteria	1. Histologically proven primary breast cancer which is thought to require mastectomy and where it is felt that cytoreductive systemic therapy would enable conservative surgery to be performed. 2. Postmenopausal up to the age of 75 years of age 3. Estrogen-receptor positive 4. Pre-treatment haematology and biochemistry values within acceptable limits 5. World Health Organisation (WHO) performance status zero or one 6. Primary breast tumour amenable to biopsy 7. Consent to having a repeat biopsy of breast tumour 8. Written informed consent prior to commencement of specific protocol procedures
Key exclusion criteria	1. Indicated for urgent neoadjuvant therapy, i.e., inflammatory or near ulcerating breast cancer 2. Bilateral invasive breast cancer 3. Any prior chemotherapy, hormone therapy or radiation for breast cancer 4. Evidence of distant metastatic disease as disclosed by bone scan, liver ultrasound scan and chest radiology 5. Past or current history of neoplasm other than breast carcinoma, except for: a. curatively treated non-melanoma skin cancer b. in situ carcinoma of the cervix c. other cancer curatively treated and with no evidence of disease for at least ten years d. ipsilateral Ductal Carcinoma In-Situ (DCIS) of the breast e. Lobular Carcinoma In-Situ (LCIS) of the breast 6. Other serious illness or medical condition: a. congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within one year from study entry, uncontrolled hypertension or high-risk uncontrolled arrhythmias b. history of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent c. active uncontrolled infection d. active peptic ulcer, unstable diabetes mellitus 7. In the opinion of the investigator, any evidence of severe or uncontrolled systemic disease such as unstable hypertension, respiratory, cardiac, hepatic, and renal disease
Date of first enrolment	01/09/2006
Date of final enrolment	31/03/2011

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Imperial College London

London
W12 0NN
United Kingdom

Sponsor information

Imperial College London (UK)
University/education

Charing Cross Campus
Fulham Palace Road
London
W6 8RF
England
United Kingdom

Website	www.ic.ac.uk
"ROR"	https://ror.org/041kmwe10

Funders

Funder type

Charity

Cancer Research UK (CRUK) (UK) (ref: C37/A9356)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Novartis Pharmaceuticals (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results				No	Yes
Results article	results	01/12/2014		Yes	No

Editorial Notes

19/03/2020: EudraCT number added.
18/10/2018: Cancer Research UK lay results summary link added to Results (plain English)