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

NCT00171704 | Completed Phase 3 Results

• 1 other identifier: CFEM345D2407
• Study Type: interventional
• Target: 263
• Locations: 2 countries
• Sites: 13

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

Keywords

Breast Cancer; Letrozole; Bone Mineral Density; Bone Markers; Serum lipid; Postmenopausal

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine (L2-l4)

  Lumbar spine (L2-L4) BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. The primary scanning site was the lumbar spine (L2 to L4) and the secondary scanning site was the total hip. All DXA scans were evaluated by a central reader.

  Baseline, 24 months

Secondary Outcomes (7)

• Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine

  Baseline, 60 months

• Percent Change From Baseline of Bone Mineral Density (BMD) of Total Hip

  Baseline, 60 months

• Median Percent Change From Baseline of Serum Markers of Bone Turnover

  Baseline, 60 months

• Percentage Change From Baseline in Serum Lipids at 5 Years

  Baseline, 60 months

• Number of Participants With Clinically Relevant Changes From Baseline in Cholesterol

  Baseline, 60 months

Study Arms (2)

Letrozole

EXPERIMENTAL

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

Drug: Letrozole

Tam-Let

EXPERIMENTAL

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

Drug: Letrozole; Drug: Tamoxifen

Interventions

Letrozole DRUG

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

Letrozole; Tam-Let

Tamoxifen 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)

Tam-Let

Eligibility Criteria

• Age: 50 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.).
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Danish Breast Cancer Cooperative Group: collaborator
• University of Sheffield: collaborator

Study Sites (13)

Novartis Investigative Site

Aalborg, Denmark

Location

Novartis Investigative Site

Aarhus, Denmark

Location

Novartis Investigative Site

Copenhagen, Denmark

Location

Novartis Investigative Site

Esbjerg, Denmark

Location

Novartis Investigative Site

Herlev, Denmark

Location

Novartis Investigative Site

Herning, Denmark

Location

Novartis Investigative Site

Hillerød, Denmark

Location

Novartis Investigative Site

Kløvervænget, Denmark

Location

Novartis Investigative Site

Roskilde, Denmark

Location

Novartis Investigative Site

Sønderborg, Denmark

Location

Novartis Investigative Site

Vejle, Denmark

Location

Novartis Investigative Site

Viborg, Denmark

Location

Novartis Investigative Site

Sheffield, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Limitations and Caveats

The study was designed to investigate the effects of letrozole compared with tamoxifen for 2 years on BMD spine (L2-L4). The study was too small to investigate the comparative efficacy of treatments on disease-free survival or on overall survival.

Results Point of Contact

• Title: Novartis Pharmaceuticals
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis

  Novartis

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 15, 2005
• Study Start: April 1, 2005
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: March 3, 2017
• Results First Posted: June 4, 2012

Record last verified: 2012-05

Locations

DK (12); GB (1)