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

This study has been completed.
Sponsor:
Collaborators:
Danish Breast Cancer Cooperative Group
University of Sheffield
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00171704
First received: September 13, 2005
Last updated: May 1, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women.
Drug: Letrozole
Drug: Tamoxifen
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine (L2-l4) [ Time Frame: Baseline, 24 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine [ Time Frame: Baseline, 60 months ] [ Designated as safety issue: Yes ]
    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.

  • Percent Change From Baseline of Bone Mineral Density (BMD) of Total Hip [ Time Frame: Baseline, 60 months ] [ Designated as safety issue: Yes ]
    Total hip 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. All DXA scans were evaluated by a central reader.

  • Median Percent Change From Baseline of Serum Markers of Bone Turnover [ Time Frame: Baseline, 60 months ] [ Designated as safety issue: No ]
    Bone turnover markers (fasting serum procollagen-I extension peptide [P1NP], C-telopeptide [CTX], skeletal bone-specific alkaline phosphatase [BSAP, N-telopeptide [NTX]) were measured at baseline/screening and at each visit thereafter. A central laboratory was used to analyze the samples. The analysis of bone markers was based on analysis of variance of the regression slopes calculated for each individual patient and each bone marker over time. In the following summary, only the median treatment group percent change from baseline (and range) at 5 years is presented for each bone marker.

  • Percentage Change From Baseline in Serum Lipids at 5 Years [ Time Frame: Baseline, 60 months ] [ Designated as safety issue: Yes ]
    Serum lipid profile (fasting serum cholesterol [total, HDL and calculated LDL], triglycerides, and lipoprotein [a]) were measured at baseline/screening and at each visit thereafter. A central laboratory was used to analyze the samples. The analysis of serum lipids was on the treatment group median percent change from baseline (and range) at 5 years.

  • Number of Participants With Clinically Relevant Changes From Baseline in Cholesterol [ Time Frame: Baseline, 60 months ] [ Designated as safety issue: Yes ]
    Serum lipid profile (fasting serum cholesterol [total, HDL and calculated LDL], triglycerides, and lipoprotein [a]) were measured at baseline/screening and at each visit thereafter. A central laboratory was used to analyze the samples. Numbers are not additive, as patients could be included in multiple rows.

  • Time to Disease Recurrence or Death [ Time Frame: 60 months ] [ Designated as safety issue: No ]
    Disease-free survival was defined as the interval between randomization and earliest confirmed event of loco-regional recurrence, distant metastases, invasive contralateral breast cancer, or death from any cause.

  • Time to Overall Survival Events [ Time Frame: 60 Months ] [ Designated as safety issue: No ]
    Overall survival was measured from date of randomization to date of death.


Enrollment: 263
Study Start Date: April 2005
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Letrozole
2.5 mg once daily (q.d.)orally for 5 years
Drug: Letrozole
2.5 mg tablets and supplied in bottles with 6-monthly supplies.
Experimental: 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.
Drug: Letrozole
2.5 mg tablets and supplied in bottles with 6-monthly supplies.
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)

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00171704

Locations
Denmark
Novartis Investigative Site
Aalborg, Denmark
Novartis Investigative Site
Arhus, Denmark
Novartis Investigative Site
Copenhagen, Denmark
Novartis Investigative Site
Esbjerg, Denmark
Novartis Investigative Site
Herlev, Denmark
Novartis Investigative Site
Herning, Denmark
Novartis Investigative Site
Hillerod, Denmark
Novartis Investigative Site
Kløvervænget, Denmark
Novartis Investigative Site
Roskilde, Denmark
Novartis Investigative Site
Sonderborg, Denmark
Novartis Investigative Site
Vejle, Denmark
Novartis Investigative Site
Viborg, Denmark
United Kingdom
Novartis Investigative Site
Sheffield, United Kingdom
Sponsors and Collaborators
Novartis Pharmaceuticals
Danish Breast Cancer Cooperative Group
University of Sheffield
Investigators
Study Chair: Novartis Novartis
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00171704     History of Changes
Other Study ID Numbers: CFEM345D2407
Study First Received: September 13, 2005
Results First Received: February 27, 2012
Last Updated: May 1, 2012
Health Authority: Denmark: Danish Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Breast Cancer
Letrozole
Bone Mineral Density
Bone Markers
Serum lipid
Postmenopausal

Additional relevant MeSH terms:
Bone Density Conservation Agents
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Letrozole
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Estrogen Antagonists
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014