A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer

NCT ID: NCT00171704

Last Updated: 2017-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 263 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30
• Study Completion Date: 2011-03-31

Brief Summary

Estrogen is known to be a regulator of bone and lipid metabolism. Letrozole is a potent inhibitor of estrogen synthesis.

This study evaluated the effects of letrozole and tamoxifen on bone and lipid metabolism in postmenopausal women with resected, receptor positive early breast cancer.

Conditions

Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Letrozole

2.5 mg once daily (q.d.)orally for 5 years

Group Type: EXPERIMENTAL

Letrozole

Intervention Type: DRUG

2.5 mg tablets and supplied in bottles with 6-monthly supplies.

Tam-Let

20 mg Tamoxifen once daily (q.d.) orally for 2 years followed by Letrozole 2.5 mg q.d. orally for 3 years.

Group Type: EXPERIMENTAL

Letrozole

Intervention Type: DRUG

2.5 mg tablets and supplied in bottles with 6-monthly supplies.

Tamoxifen

Intervention Type: DRUG

20 mg tablets in bottles as 6-monthly supplies (supplied to Novartis as Tamofen from Schering Oy, Subsidiary of Schering AG, Pansiontie 47, FIN-2010 Turku, Finland)

Interventions

Letrozole

2.5 mg tablets and supplied in bottles with 6-monthly supplies.

Intervention Type: DRUG

Tamoxifen

20 mg tablets in bottles as 6-monthly supplies (supplied to Novartis as Tamofen from Schering Oy, Subsidiary of Schering AG, Pansiontie 47, FIN-2010 Turku, Finland)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Female
• Post-menopausal hormone status defined as:
• Patients with menostasis (amenorrhea) > 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 was determined on the basis of follicle-stimulating hormone (FSH)/luteinizing hormone (LH) values.
• Histologically confirmed resected breast cancer and eligible for adjuvant endocrine therapy. As a minimum, patients had to have receptor-positive tumors, which were defined either as estrogen receptor (ER) and/or progesterone receptor (PgR) ≥ 10 fmol/mg cytosol protein; or ≥ 10% of the tumor cells positive by immunocytochemical evaluation.
• Adequate bone marrow function (white blood cell count [WBC] > 3.0 x 109 /L, platelets ≥ 100.0 x 109 /L, and hemoglobin > 10 g/dL).
• Documented evidence of adequate renal function (creatinine < 180 µmol/L) and hepatic function (bilirubin < 30 µmol/L, alanine aminotransferase (ALT) < 1.5 x upper normal limit of the laboratory).
• Life expectancy of at least 24 months at the time of enrollment.
• Written voluntary informed consent prior to initiation of any study procedure.
• 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.

Exclusion Criteria

• Patients with distant metastases as defined by the criteria of the Danish Breast Cancer Co-operative Group (DBCCOG).
• Pre-existing bone disease (e.g. osteomalacia, osteogenesis imperfecta, Paget's disease).
• Patients receiving bisphosphonates for more than 3 months before randomization.
• Chronic treatment with drugs known to interfere with bone metabolism, e.g.
• Anti-convulsants 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 (prior to randomization).
• 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 coumarin derivatives and heparin at the time of randomization.
• Metabolic diseases known to interfere with bone metabolism (e.g., Hyperparathyroidism, hypoparathyroidism, uncontrolled thyroid disease, Cushing's disease, vitamin D deficiency, malabsorption syndrome, etc.).
• Treatment with lipid-lowering agents within the 3 months prior to randomization (this exclusion criterion did not apply to patients randomized in the United Kingdom).
• Patients receiving other anti-cancer treatment.
• Previous neoadjuvant / adjuvant chemotherapy and /or previous adjuvant endocrine therapy (e.g., anti-estrogens, AIs).
• 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 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 were excluded. Patients with invasive bilateral breast cancer were excluded. Patients with vaginal discharge/ vaginal bleeding with evidence of malignancy were excluded.
• Any other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, etc.) which would prevent prolonged follow-up.

• Minimum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Danish Breast Cancer Cooperative Group

OTHER

Sponsor Role: collaborator

University of Sheffield

OTHER

Sponsor Role: collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis

Role: STUDY_CHAIR

Novartis

Locations

Novartis Investigative Site

Aalborg, , Denmark

Novartis Investigative Site

Aarhus, , Denmark

Novartis Investigative Site

Copenhagen, , Denmark

Novartis Investigative Site

Esbjerg, , Denmark

Novartis Investigative Site

Herlev, , Denmark

Novartis Investigative Site

Herning, , Denmark

Novartis Investigative Site

Hillerød, , Denmark

Novartis Investigative Site

Kløvervænget, , Denmark

Novartis Investigative Site

Roskilde, , Denmark

Novartis Investigative Site

Sønderborg, , Denmark

Novartis Investigative Site

Vejle, , Denmark

Novartis Investigative Site

Viborg, , Denmark

Novartis Investigative Site

Sheffield, , United Kingdom

Countries

Denmark; United Kingdom

Other Identifiers

CFEM345D2407

Identifier Type: -

Identifier Source: org_study_id