Clinical trial NCT00171704: A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer
Official title: A Study to Evaluate the Effect of Letrozole and Tamoxifen on Bone and Lipids in Postmenopausal Women With Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hormone Sensitive Resected Primary Breast Cancer in Postmenopausal Women
Keywords: Breast Cancer
Letrozole
Bone Mineral Density
Bone Markers
Serum lipid
Postmenopausal
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Danish Breast Cancer Cooperative Group
name: University of Sheffield
First posted: 2005-09-15
Enrollment: 263
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine (L2-l4)
timeFrame: Baseline, 24 months
Secondary outcomes:
measure: Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine
timeFrame: Baseline, 60 months
measure: Percent Change From Baseline of Bone Mineral Density (BMD) of Total Hip
timeFrame: Baseline, 60 months
measure: Median Percent Change From Baseline of Serum Markers of Bone Turnover
timeFrame: Baseline, 60 months
measure: Percentage Change From Baseline in Serum Lipids at 5 Years
timeFrame: Baseline, 60 months
measure: Number of Participants With Clinically Relevant Changes From Baseline in Cholesterol
timeFrame: Baseline, 60 months
measure: Time to Disease Recurrence or Death
timeFrame: 60 months
measure: Time to Overall Survival Events
timeFrame: 60 Months
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Novartis Investigative Site
city: Arhus
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Esbjerg
country: Denmark
facility: Novartis Investigative Site
city: Herlev
country: Denmark
facility: Novartis Investigative Site
city: Herning
country: Denmark
facility: Novartis Investigative Site
city: Hillerod
country: Denmark
facility: Novartis Investigative Site
city: Kløvervænget
country: Denmark
facility: Novartis Investigative Site
city: Roskilde
country: Denmark
facility: Novartis Investigative Site
city: Sonderborg
country: Denmark
facility: Novartis Investigative Site
city: Vejle
country: Denmark
facility: Novartis Investigative Site
city: Viborg
country: Denmark
facility: Novartis Investigative Site
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis
name: Novartis
role: STUDY_CHAIR
References: