Molecular profiling of post-menopausal women with breast cancer on Neoadjuvant Endocrine Therapy with tamoxifen or exemestane
| ISRCTN | ISRCTN87408408 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN87408408 |
| Secondary identifying numbers | 2 |
- Submission date
- 12/12/2006
- Registration date
- 26/01/2007
- Last edited
- 27/05/2014
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Contact information
Dr Helena Earl
Scientific
Scientific
Lecturer and Honorary Consultant
Department of Oncology
Box 193, Oncology Canter
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 2QQ
United Kingdom
| Phone | +44 (0)1223 336800 |
|---|
Study information
| Study design | Randomised phase II open-label translational study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | |
| Study acronym | MoNET |
| Study objectives | 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(s) | Cambridge Local Research Ethics Committee, 21/05/2006 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/01/2007 |
| Completion date | 01/05/2011 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Not Specified |
| Sex | Female |
| Target number of participants | 100 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/01/2007 |
| Date of final enrolment | 01/05/2011 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Lecturer and Honorary Consultant
Cambridge
CB2 2QQ
United Kingdom
CB2 2QQ
United Kingdom
Sponsor information
Cambridge University Hospitals NHS Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 2QQ
England
United Kingdom
"ROR" |
https://ror.org/04v54gj93 |
|---|
Funders
Funder type
Industry
Cambridge University Hospitals NHS Foundation Trust (UK)
No information available
Pfizer Limited (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 |
