E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bone loss attributed to cessation of ovarian estrogen production is common in postmenopausal women. In postmenopausal women with breast cancer, treatment with an aromatase inhibitor may further reduce or eliminate estrogen activity, leading to potential acceleration of bone loss. This study will evaluate the effects of letrozole and tamoxifen on bone and lipid metabolism in postmenopausal women with rersected, receptor positive early breast cancer |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of letrozole versus tamoxifen on the bone mineral density (BMD) of the lumbar spine (L2 to L4) as measured by dual energy X-ray absorptiometry (DXA) at 2 years in postmenopausal women with resceted hormone receptor-positive primary breast cancer. The primary enpoint is therefore percent change from baseline in lumbar spine (L2-L4) BMD at 2 years. |
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E.2.2 | Secondary objectives of the trial |
To evaluate teh effect of long-term use of letrozole on bone mineral density, marker of bone metabolism, and fasting serum lipid profile in teh adjuvant treatment of postmenopausal women with resected hormone receptor-positive breast cancer. Those parameters will be evaluated as a function of treatment time. In addition, general safety and efficacy will be evaluated as well as a secondary objective. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Female sex. 2. Postmenopausal hormone status defined as: •Patients with menostasis > 12 months or history of oophorectomy •Patients ≥ 55 years with history of hysterectomy or having continued/renewed menstruation on cyclic hormone treatment •Patients of 50-54 years: Menopausal status is determined on the basis of FSH/LH values 3. Histologically confirmed resected breast cancer AND eligible for adjuvant endocrine therapy. As a minimum, patients must have receptor positive tumours, which is defined either as ER and/or PgR ≥10 fmol/mg cytosol protein; or ≥ 10% of the tumour cells positive by immunocytochemical evaluation. 4. Adequate bone marrow function (WBC > 3.0 x 10 9 /L, platelets ≥ 100.0 x 10 9 /L, and haemoglobin > 10 g/dL). 5. Documented evidence of adequate renal function (creatinine < 180 µmol/L) and hepatic function (bilirubin < 30 µmol/L, ALT (SGPT) < 1.5 x upper normal limit of the laboratory). 6. Life expectancy at least 24 months. 7. Written voluntary informed consent prior to initiation of any study procedure. 8. Willingness to undergo all scheduled tests and examinations for evaluation of bone density and bone metabolism, and lipid profiles in addition to the standard assessments for monitoring their breast cancer status.
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E.4 | Principal exclusion criteria |
If any of the following criteria is met, the patient is not eligible for the study. 1. Patients with distant metastases as defined by the criteria of the Danish Breast cancer group. 2. Pre-existing bone disease (e.g. osteomalacia, osteogenesis imperfecta, Paget’s disease). 3. Patients receiving bisphosphonates for more than 3 months before randomization. 4. Chronic treatment with drugs known to interfere with bone metabolism, e.g. •Anticonvulsants within the past year. •Corticosteroids at doses greater than the equivalent of 5 mg/day prednisone for more than two weeks in the past 6 months. •Any previous treatment with sodium fluoride at daily doses ≥ 5 mg/day for a period exceeding 1 month. •Anabolic steroids in the past 12 months. •Long term use of coumarins derivatives and heparin at the time of randomization. 5. Metabolic diseases known to interfere with bone metabolism (e.g. Hyper-, Hypoparathyroidism, uncontrolled thyroid disease, Cushing Disease, Vitamin D deficiency, Malabsorption Syndrome, etc.). 6. Treatment with lipid lowering agents within the 3 months prior to randomization (this exclusion criteria does not apply to patients randomized in the UK). 7. Patient receiving other anti-cancer treatment. 8. Previous neoadjuvant / adjuvant chemotherapy and/or previous adjuvant endocrine therapy (eg anti-estrogens, aromatase inhibitors). 9. History of previous or concomitant malignancy within the past 5 years other than adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease free for five years. Patients with endometrial cancer and/or invasive breast cancer at any time in their medical history are excluded. Patients with invasive bilateral breast cancer are excluded. Patients with vaginal discharge/vaginal bleeding with evidence of malignancy are excluded. 10. Any other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, etc.) which would prevent prolonged follow-up. 11. History of cardiovascular diseases (including earlier known acute myocardial infarction or angina pectoris), cerebrovascular events, venous thromboembolic events (including deep-vein thromboses). 12. History of non-compliance to medical regimens and patients who are considered potentially unreliable. 13. History of systemic investigational drugs use within the past 30 days. 14. Presence 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. 15. Current use of hormone replacement therapy (HRT must be stopped at least 4 weeks before study treatment is initiated).
Additional exclusion criteria for spine DXA: 1. History of complaints, or surgery of the lumbosacral spine, with or without implantable devices. 2. Any disease of the spine that would preclude the proper acquisition or assessment of a lumbar spine DXA (e.g. degenerative joint disease) to ensure that the interpretation of DXA scan is not affected by anatomical artifacts. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in lumbar spine (L2-L4) bone mineral density |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |