Bone Density and Bone Loss in Postmenopausal Women With Breast Cancer Receiving Treatment in Clinical Trial IBCSG-1-98

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
International Breast Cancer Study Group
ClinicalTrials.gov Identifier:
NCT00369850
First received: August 24, 2006
Last updated: July 26, 2012
Last verified: July 2012
  Purpose

RATIONALE: Diagnostic procedures, such as bone mineral density testing and x-ray, help measure bone loss in women receiving treatment for breast cancer. The test results may help doctors plan better treatment.

PURPOSE: This phase III trial is studying bone density and bone loss in postmenopausal women with breast cancer receiving treatment in clinical trial IBCSG-1-98.


Condition Intervention Phase
Breast Cancer
Osteoporosis
Other: laboratory biomarker analysis
Procedure: Dual energy X-ray absorptiometry (DEXA)
Procedure: Spine X-ray
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Investigating Bone Density and Bone Loss Without Baseline Information

Resource links provided by NLM:


Further study details as provided by International Breast Cancer Study Group:

Primary Outcome Measures:
  • Relative percent change of bone mineral density (BMD) form baseline to after 2, 3, 4, or 5 years of treatment on protocol IBCSG-1-98 [ Time Frame: 5 years after randomisation to BIG 1-98 ] [ Designated as safety issue: No ]
  • Recovery of BMD at 1 year after the completion of treatment on protocol IBCSG-1-98 [ Time Frame: 6 years after randomisation to BIG 1-98 ] [ Designated as safety issue: No ]
  • Proportion of patients with BMD below the absolute threshold value for osteoporosis [ Time Frame: 5 years after randomisation to BIG 1-98 ] [ Designated as safety issue: No ]
  • Relative percent change in markers of bone resorption from baseline to after 2, 3, 4, or 5 years of treatment on protocol IBCSG-1-98 [ Time Frame: 5 years after randomisation to BIG 1-98 ] [ Designated as safety issue: No ]
  • Recovery of the markers of bone resorption at 1 year after the completion of treatment on protocol IBCSG-1-98 [ Time Frame: 6 years after randomisation to BIG 1-98 ] [ Designated as safety issue: No ]

Enrollment: 458
Study Start Date: May 2004
Study Completion Date: January 2012
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tamoxifen for 5 years
Patients treated with tamoxifen for 5 years after randomisation.
Other: laboratory biomarker analysis
Biomarkers (C-telopeptide, osteocalcin and skeletal alkaline phosphatase) will be assessed in serum.
Procedure: Dual energy X-ray absorptiometry (DEXA)
Mone mineral density measurements of L2-L4 and hip will be performed using DEXA.
Procedure: Spine X-ray
Thoracic and lumbar X-ray (T4-L4, lateral projection) will be performed.
Experimental: Letrozole for 5 years
Patients treated with letrozole for 5 years after randomisation.
Other: laboratory biomarker analysis
Biomarkers (C-telopeptide, osteocalcin and skeletal alkaline phosphatase) will be assessed in serum.
Procedure: Dual energy X-ray absorptiometry (DEXA)
Mone mineral density measurements of L2-L4 and hip will be performed using DEXA.
Procedure: Spine X-ray
Thoracic and lumbar X-ray (T4-L4, lateral projection) will be performed.
Experimental: Tamoxifen 2 years plus letrozole 3 years
Patients treated with tamoxifen for 2 years and afterwards with letrozole for 3 years.
Other: laboratory biomarker analysis
Biomarkers (C-telopeptide, osteocalcin and skeletal alkaline phosphatase) will be assessed in serum.
Procedure: Dual energy X-ray absorptiometry (DEXA)
Mone mineral density measurements of L2-L4 and hip will be performed using DEXA.
Procedure: Spine X-ray
Thoracic and lumbar X-ray (T4-L4, lateral projection) will be performed.
Experimental: Letrozole 2 years plus tamoxifen 3 years
Patients treated with letrozole for 2 years and afterwards with tamoxifen for 3 years.
Other: laboratory biomarker analysis
Biomarkers (C-telopeptide, osteocalcin and skeletal alkaline phosphatase) will be assessed in serum.
Procedure: Dual energy X-ray absorptiometry (DEXA)
Mone mineral density measurements of L2-L4 and hip will be performed using DEXA.
Procedure: Spine X-ray
Thoracic and lumbar X-ray (T4-L4, lateral projection) will be performed.

Detailed Description:

OBJECTIVES:

  • Compare the effects on bone mineral density (BMD) in the L2-L4 (posterio-anterior) region of the spine and hip by assessing bone density in postmenopausal women with breast cancer receiving treatment on protocol IBCSG-1-98.
  • Compare the incidence of radiological gross changes and fractures identified from spine x-rays (T4-L4) in these patients (in groups 1 and 2).
  • Use longitudinal BMD measurements to estimate a linear rate of bone loss based on mixed effect models.
  • Identify serum markers for bone loss to determine how they correlate with osteoporosis, microfractures, clinical fractures, and breast cancer-related bone events.

OUTLINE: This is a multicenter study and a substudy of protocol IBCSG-1-98. Patients are assigned to 1 of 3 groups according to the length of treatment they have undergone on protocol IBCSG-1-98.

  • Group 1 (prior to or at the end of the second year of treatment on protocol IBCSG-1-98): Patients undergo bone mineral density (BMD) testing of the L2-L4 spine and hip at baseline and years 1, 2, 3, and 4 from baseline. They also undergo x-rays of the T4-L4 spine at baseline and years 1, 3, and 4 from baseline.
  • Group 2 (after 2 years but before the end of the third year of treatment on protocol IBCSG-1-98): Patients undergo BMD testing of the L2-L4 spine and hip at baseline and years 1, 2, and 3 from baseline. They also undergo x-rays of the T4-L4 spine at baseline and years 2 and 3 from baseline.
  • Group 3 (after 3 years but before the end of the fifth year of treatment on protocol IBCSG-1-98): Patients undergo BMD testing of the L2-L4 spine and hip at baseline and years 1 and 2 from baseline (for patients in 4th year of treatment) or year 1 from baseline (for patients in 5th year of treatment).

Patients undergo blood collection at baseline and periodically during study for biomarker correlative study.

PROJECTED ACCRUAL: A total of 660 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of breast cancer

    • Resected disease
  • Enrolled on protocol IBCSG-1-98

    • Receiving adjuvant endocrine therapy comprising 1 of the following regimens:

      • Letrozole
      • Tamoxifen
      • Letrozole after 2 years of tamoxifen
      • Tamoxifen after 2 years of letrozole
    • Not yet completed 5 years of treatment
  • No breast cancer recurrence or second primary cancer
  • No known, symptomatic bone disease, including osteomalacia or osteogenesis imperfecta
  • No prior registration to protocol IBCSG-1-98 Bone Mineral Density substudy
  • Hormone receptor status:

    • Estrogen receptor-positive and/or progesterone receptor-positive tumor

PATIENT CHARACTERISTICS:

  • Female
  • Postmenopausal
  • No uncontrolled thyroid or parathyroid disease, Cushing's disease, or other pituitary diseases
  • No malabsorption syndrome or clinically relevant vitamin D deficiency
  • No patients for whom the bone density determination is impossible

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 1 year since prior and no concurrent anticonvulsants
  • More than 6 weeks since prior and no concurrent corticosteroids (at doses > the equivalent of 5 mg/day prednisone) for > 2 weeks total
  • No prior or concurrent sodium fluoride (at daily doses ≥ 5 mg/day) for > 1 month
  • More than 12 months since prior and no concurrent anabolic steroids
  • More than 6 months since prior treatment, either investigational or not, for the prevention of osteoporosis (excluding calcium or cholecalciferol [vitamin D])
  • No concurrent raloxifene
  • Concurrent therapeutic intervention for osteoporosis comprising bisphosphonates allowed
  • Concurrent warfarin allowed provided it is given for ≤ 4 weeks
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00369850

Locations
Australia, New South Wales
Institute of Oncology at Prince of Wales Hospital
Randwick, New South Wales, Australia, 2031
Australia, Queensland
Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia, 4029
France
Institut Bergonie
Bordeaux, France, 33076
Italy
Centro di Riferimento Oncologico - Aviano
Aviano, Italy, 33081
Ospedali Riuniti di Bergamo
Bergamo, Italy, 24100
European Institute of Oncology
Milano, Italy, 20141
New Zealand
Dunedin Hospital
Dunedin, New Zealand
Peru
Instituto Nacional de Enfermedades Neoplasicas
Lima, Peru, 34
South Africa
Groote Schuur Hospital
Cape Town, South Africa, 7925
Spain
Hospital Ruber Internacional
Madrid, Spain, 28034
Switzerland
Kantonspital Aarau
Aarau, Switzerland, CH-5001
Inselspital Bern
Bern, Switzerland, CH-3010
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Ospedale Beata Vergine
Mendrisio, Switzerland, CH-6850
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Regionalspital
Thun, Switzerland, 3600
Sponsors and Collaborators
International Breast Cancer Study Group
Investigators
Study Chair: Stefan Aebi, MD University Hospital Inselspital, Berne
Study Chair: Andrea Decensi, MD European Institute of Oncology
  More Information

Additional Information:
No publications provided by International Breast Cancer Study Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: International Breast Cancer Study Group
ClinicalTrials.gov Identifier: NCT00369850     History of Changes
Other Study ID Numbers: CDR0000482381, IBCSG-18-98-BS, EU-20623, IBCSG-1-98-BS, NOVARTIS-2026703019
Study First Received: August 24, 2006
Last Updated: July 26, 2012
Health Authority: United States: Federal Government

Keywords provided by International Breast Cancer Study Group:
osteoporosis
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer

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

ClinicalTrials.gov processed this record on September 15, 2014