Plain English Summary
Trial website
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 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 trial start date
01/09/2006
Overall trial end date
31/03/2011
Reason abandoned (if study stopped)
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
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
Basic results (scientific)
Publication list
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25395314