An open-label, randomized, multicenter safety study to evaluate the skeletal and lipid profile effects of letrozole and tamoxifen in postmenopausal women with resected, receptor positive early breast cancer - N/A

• Register: EUCTR
• Last refreshed on: 1 May 2012
• Main ID: EUCTR2004-002418-12-DK
• Date of registration: 11/01/2005
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: An open-label, randomized, multicenter safety study to evaluate the skeletal and lipid profile effects of letrozole and tamoxifen in postmenopausal women with resected, receptor positive early breast cancer - N/A
• Scientific title: An open-label, randomized, multicenter safety study to evaluate the skeletal and lipid profile effects of letrozole and tamoxifen in postmenopausal women with resected, receptor positive early breast cancer - N/A
• Date of first enrolment: 25/01/2005
• Target sample size: 245
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-002418-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Denmark, United Kingdom

Key inclusion & exclusion criteria

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.
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

Exclusion criteria:
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 U.K.).
7. Patient receiving other anti-cancer treatment.
8. Previous neoadjuvant / adjuvant chemotherapy and /or previous adjuvant endocrine therapy (e.g. 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)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

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 resected, receptor positive early breast cancer.

Intervention(s)

Product Name: Femar
Product Code: FEM345
Pharmaceutical Form: Tablet
INN or Proposed INN: letrozole
CAS Number: 112809-51-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Product Name: Tamofen
Pharmaceutical Form: Tablet
INN or Proposed INN: tamoxifen
CAS Number: 10540-29-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Primary end point(s): The primary endpoint is percent change from baseline in lumbar spine (L2-L4) bone mineral density at 2 years.

Secondary Objective: The secondary objectives of this study are to evaluate the effect of long-term use of letrozole on bone mineral density, markers of bone metabolism, and fasting serum lipid profile in the 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.

Main Objective: The primary objective of this study is 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 resected hormone receptor-positive primary breast cancer. The primary endpoint is therefore percent change from baseline in lumbar spine (L2-L4) BMD at 2 years.

Secondary ID(s)

N/A

CFEM345D2407