Condition category
Cancer
Date applied
12/12/2006
Date assigned
26/01/2007
Last edited
27/05/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Helena Earl

ORCID ID

Contact details

Lecturer and Honorary Consultant
Department of Oncology
Box 193
Oncology Canter
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 2QQ
United Kingdom
+44 (0)1223 336800

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

2

Study information

Scientific title

Acronym

MoNET

Study hypothesis

Neoadjuvant (or primary) endocrine therapy is an ideal platform for predictive or prognostic marker discovery. Although neoadjuvant and adjuvant endocrine therapy are both well-established treatments, their molecular basis remains incompletely understood. There are no predictive or prognostic markers except oestrogen receptor status that can be used to tailor treatment. This study will use neoadjuvant setting as a basis to identify molecular markers of sensitivity and resistance.

On 22/02/2011 the anticipated end date for this trial was updated from 01/01/2010 to 01/05/2011.

Ethics approval

Cambridge Local Research Ethics Committee, 21/05/2006

Study design

Randomised phase II open-label translational study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Localised or locally advanced early breast cancer

Intervention

Patients will be given 16 weeks of neoadjuvant endocrine therapy with tamoxifen (20 mg orally [PO]) or exemestane (25 mg PO) and would have tumour biopsies taken pre-treatment, at the midpoint and a sample taken at the end of treatment for molecular marker studies.

Intervention type

Drug

Phase

Phase II

Drug names

Tamoxifen, exemestane

Primary outcome measures

Identify molecular markers that would predict the response or resistance to endocrine therapy with exemestane or tamoxifen.

Secondary outcome measures

1. Clinical Response Rate (cRR)
2. Radiological Response Rate (rRR)
3. Changes in Ki67 counts in response to therapy
4. Clinical/radiological response among patients over-expressing Epidermal Growth Factor Receptor (EGFR)/Human Epidermal growth factor Receptor 2 (HER-2)
5. Serum levels of Vascular Endothelial Growth Factor Receptors (VEGF-R) and Vascular Endothelial Growth Factor (VEGF) before, during and after treatment
6. Serum circulatory HER-2 Extracellular Domain (ECD) and Circulating Endothelial Cells (CEC) changes during treatment
7. Vascular Endothelial Growth Factor A (VEGFA), Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1) and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) expression and correlation with clinical outcomes
8. Cadherin-11, transcription factor (Activating Protein–1 [AP-1], Ets-2, cyclin D1)
9. Gene profiling to identify molecular markers of response or resistance

Overall trial start date

01/01/2007

Overall trial end date

01/05/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Women with histological diagnosis of primary invasive breast cancer on core biopsy
2. Not a candidate for chemotherapy
3. Localised or locally advanced breast cancer
4. Ultrasound size at least 2 cm:
a. unifocal tumour:
i. T2 or T3 tumours (radiological size more than 20 mm)
ii. T4 tumour of any size with direct extension to either chest wall or skin
iii. inflammatory carcinoma with tumour of any size
OR
b. other locally advanced disease:
i. clinical and radiological involvement of axillary lymph node (radiological diameter more than 20 mm) and primary breast tumour of any diameter
ii. where no primary breast tumour was found, the presence of breast cancer in a Lymph Node (LN) must be histopathologically confirmed by LN biopsy (Tru-cut or whole LN)
OR
c. multifocal tumour:
i. the sum of the tumour diameters must be more than 20 mm (radiological size more than 20 mm)
ii. patients with bilateral disease are eligible to enter the trial
iii. no previous treatment for breast cancer
5. Oestrogen Receptor (ER) positive (Allred score more than or equal to four)
6. Palpable and measurable disease in the breast or axilla
7. Post-menopausal defined by following criteria: cessation of menstrual periods for at least 1 year or bilateral surgical oophorectomy or Follicular Stimulating Hormone (FSH) and oestradiol in the post-menopausal range
8. At least 2 weeks since prior hormone replacement therapy or phyto-oestrogens herbal, alternative, or Over-The Counter (OTC) sex hormone remedies and not on concomitant hormonal therapy with these agents
9. Eastern Cooperative Oncology Group (ECOG) performance status zero, one or two
10. Randomisation and treatment within 4 weeks of biopsy
11. Patient must have adequate bone marrow, hepatic and renal function
12. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
13. Written consent for the trial

Participant type

Patient

Age group

Not Specified

Gender

Female

Target number of participants

100

Participant exclusion criteria

1. Patient unfit to receive endocrine-based therapy
2. Previous history of cancer excluding basal cell carcinoma, cervical carcinoma in-situ, or ductal carcinoma in situ of the breast
3. Previous deep vein thrombosis or pulmonary embolism

Recruitment start date

01/01/2007

Recruitment end date

01/05/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Lecturer and Honorary Consultant
Cambridge
CB2 2QQ
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Trust (UK)

Sponsor details

Addenbrooke's Hospital
Hills Road
Cambridge
CB2 2QQ
United Kingdom

Sponsor type

Government

Website

Funders

Funder type

Industry

Funder name

Cambridge University Hospitals NHS Foundation Trust (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Pfizer Limited (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

Publication citations

Additional files

Editorial Notes