eoadjuvant hormone therapy for postmenopausal women with ER and/or PgR positive primary breast cancer: A multi-center study to determine the optimum length of treatment with Femara (letrozole 2.5mg daily) on tumour regression to permit breast conserving surgery.
- Conditions
- Postmenopausal women with ER and/or PgR positive primary breast cancer
- Registration Number
- EUCTR2005-000661-19-GB
- Lead Sponsor
- ovartis Pharmaceuticals UK Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- Not specified
1. Postmenopausal women able to comply with the protocol requirements with primary invasive breast cancer, histologically confirmed by core needle biopsy (see appendix I: Preparation of core biopsies), whose tumours are estrogen (ER) and / or progesterone (PgR) positive, defined by core biopsy immunohistochemistry with > 30% positive malignant epithelial cells. Where tumours are bilateral, the reference side should be that with the larger or largest tumour at baseline.
2. Clinical Stage T2 or >T2 tumours which in the investigators opinion would not be eligible for breast-conserving surgery. The nodal status will be evaluated by palpation and/or ultrasound.
3. Post menopausal status defined by one of the following:
Women with an intact uterus and
= 55 years of age OR
< 55 years of age without menses for the last 5 years OR
< 55 years of age and has not had menses for at least the last 12 months (but has had menses in the last 5 years) and has postmenopausal levels of FSH (according to the postmenopausal range of the individual laboratory, and performed at least four weeks after stopping HRT/oral contraceptives).
OR In the case of women without an intact uterus and
= 55 years of age OR
>55 years of age and postmenopausal levels of FSH (according to the postmenopausal range of the individual laboratory, and performed at least four weeks after stopping HRT/oral contraceptives)
Bilateral oophorectomy (prior to the diagnosis of breast cancer).
4. Tumour measurable by clinical examination, mammography and ultrasound.
5. Adequate bone marrow function as shown by: WBC =3.5 x 109/L, ANC = 1.5 x 109/L, Platelets = LLN, Hb >10g/dL.
6. Adequate liver function as shown by: serum bilirubin = 1.5 x ULN, albumin = 3 g/dl, serum transaminases activity = 2.5 x ULN, alkaline phosphatase = 2.5 x ULN.
7. Normal renal function (serum creatinine = 1.5 x ULN, BUN = 1.5 x ULN).
8. A life expectancy of at least 6 months.
9. Written informed consent to the core study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Multifocal disease
2. Prior treatment with aromatase inhibitors or antiestrogens, or known hypersensitivity to these compounds.
3. Uncontrolled endocrine disorders such as diabetes mellitus, confirmed hyper- or hypothyroidism, Cushing´s Syndrome, Addison´s disease (treated or untreated).
4. Patients with unstable angina, uncontrolled cardiac disease (e.g. Class III or IV New York Heart Association's Functional Classification).
5. Patients who are eligible for breast conserving surgery.
6. Evidence of inflammatory breast cancer or distant metastasis.
7. Other concurrent malignant disease with the exception of cone-biopsied in situ carcinoma of the cervix uteri, or adequately treated basal or squamous cell carcinoma of the skin, or other curable cancers e.g. Hodgkin´s disease or NHL, provided 5 years have elapsed from completion of therapy, and there has been no recurrence.
8. Concomitant anti-cancer treatments such as chemotherapy, immunotherapy/biological response modifiers (BRM’s), endocrine therapy (including steroids), bisphosphonate therapy and radiotherapy. Bisphosphonate therapy for osteoporosis is NOT excluded, and can be continued as concomitant therapy. Patients who have received HRT will NOT be excluded, provided that HRT is discontinued at least 2 weeks prior to entry into the study.
9. Concomitant treatment with steroids, e.g. glucocorticoids for indications other than cancer, except aerosol for obstructive airways diseases and steroid injection to the joints for treatment of inflammation.
10. Other investigational drugs within the past 30 days and the concomitant use of investigational drugs.
11. History of non-compliance to medical regimens and patients who are considered potentially unreliable.
12. Any history of frank or uncontrolled osteoporosis (anti-osteoporotic treatment is permitted).
13. History of any other condition which may effect participation in the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the optimal treatment duration with letrozole (2.5 mg daily) preoperatively in order to permit breast conserving surgery in patients with early breast cancer, who are initially not suitable for breast conserving surgery at study entry. Response will be assessed by clinical examination and breast ultrasound.;Secondary Objective: To determine the reduction in tumour volume every 2 months throughout the study.<br>To determine the response rate in line with the RECIST criteria<br>To monitor the long term (5-year) local recurrence rate.<br>To establish the safety and tolerability of the treatment prior to surgery.<br><br><br>Exploratory biomarker research; to evaluate the effects of Letrozole on breast tumour biomarkers.<br>;Primary end point(s): Tumour response sufficient for breast conserving surgery.
- Secondary Outcome Measures
Name Time Method