Condition category
Cancer
Date applied
31/05/2006
Date assigned
13/07/2006
Last edited
08/04/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Charles R Coombes

ORCID ID

Contact details

Faculty of Medicine
Imperial College London
Hammersmith Hospitals NHS Trust
8th Floor
MRC Cyclotron Building
Du Cane Road
London
W12 0NN
United Kingdom
+44 (0)20 8383 5828
c.coombes@imperial.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00963729

Protocol/serial number

N/A

Study information

Scientific title

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

Acronym

Neo-CENT

Study hypothesis

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

Leeds (East) Research Ethics Committee on 23/01/2008 (ref: 07/H1306/164).

Study design

Multi-centre randomised parallel-group comparative phase III trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

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

Phase

Phase III

Drug names

Epirubicin, cyclophosphamide, fluorouracil and letrozole

Primary outcome measures

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 trial start date

01/09/2006

Overall trial end date

31/03/2011

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

40 for feasibility study and 676 for main study (716 total)

Participant 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

Recruitment start date

01/09/2006

Recruitment end date

31/03/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Imperial College London
London
W12 0NN
United Kingdom

Sponsor information

Organisation

Imperial College London (UK)

Sponsor details

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

Sponsor type

University/education

Website

www.ic.ac.uk

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK) (ref: C37/A9356)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Novartis Pharmaceuticals (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25395314

Publication citations

Additional files

Editorial Notes