Plain English Summary
Trial website
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 measure
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 (if study stopped)
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
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
Basic results (scientific)
Publication list