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

Breast Cancer Clinical Trial

Official title:

Investigating Bone Density and Bone Loss Without Baseline Information

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00369850
• Other study ID #: CDR0000482381
• Secondary ID: IBCSG-18-98-BSEU
• Status: Completed
• Phase: Phase 3
• First received: August 24, 2006
• Last updated: July 26, 2012
• Start date: May 2004
• Est. completion date: January 2012

Study information

• Verified date: July 2012
• Source: International Breast Cancer Study Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 458
• Est. completion date: January 2012
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 30 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Osteoporosis

Intervention

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.
• Spine X-ray
Thoracic and lumbar X-ray (T4-L4, lateral projection) will be performed.

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Institute of Oncology at Prince of Wales Hospital	Randwick	New South Wales
France	Institut Bergonie	Bordeaux
Italy	Centro di Riferimento Oncologico - Aviano	Aviano
Italy	Ospedali Riuniti di Bergamo	Bergamo
Italy	European Institute of Oncology	Milano
New Zealand	Dunedin Hospital	Dunedin
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
South Africa	Groote Schuur Hospital	Cape Town
Spain	Hospital Ruber Internacional	Madrid
Switzerland	Kantonspital Aarau	Aarau
Switzerland	Inselspital Bern	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Ospedale Beata Vergine	Mendrisio
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	Regionalspital	Thun

Sponsors (1)

Lead Sponsor	Collaborator
International Breast Cancer Study Group

Countries where clinical trial is conducted

Australia,  France,  Italy,  New Zealand,  Peru,  South Africa,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		5 years after randomisation to BIG 1-98	No
Primary	Recovery of BMD at 1 year after the completion of treatment on protocol IBCSG-1-98		6 years after randomisation to BIG 1-98	No
Primary	Proportion of patients with BMD below the absolute threshold value for osteoporosis		5 years after randomisation to BIG 1-98	No
Primary	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		5 years after randomisation to BIG 1-98	No
Primary	Recovery of the markers of bone resorption at 1 year after the completion of treatment on protocol IBCSG-1-98		6 years after randomisation to BIG 1-98	No