Clinical trial NCT00369850: Bone Density and Bone Loss in Postmenopausal Women With Breast Cancer Receiving Treatment in Clinical Trial IBCSG-1-98
Official title: Investigating Bone Density and Bone Loss Without Baseline Information
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Osteoporosis
Keywords: osteoporosis
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
Lead sponsor: ETOP IBCSG Partners Foundation
Sponsor class: NETWORK
First posted: 2006-08-29
Enrollment: 458
Sex: FEMALE
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: 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
timeFrame: 5 years after randomisation to BIG 1-98
measure: Recovery of BMD at 1 year after the completion of treatment on protocol IBCSG-1-98
timeFrame: 6 years after randomisation to BIG 1-98
measure: Proportion of patients with BMD below the absolute threshold value for osteoporosis
timeFrame: 5 years after randomisation to BIG 1-98
measure: 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
timeFrame: 5 years after randomisation to BIG 1-98
measure: Recovery of the markers of bone resorption at 1 year after the completion of treatment on protocol IBCSG-1-98
timeFrame: 6 years after randomisation to BIG 1-98
Secondary outcomes:
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: Institute of Oncology at Prince of Wales Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Bordeaux
country: France
facility: Institut Bergonie
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - Aviano
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo
city: Milano
country: Italy
facility: European Institute of Oncology
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplasicas
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
city: Aarau
country: Switzerland
facility: Kantonspital Aarau
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Mendrisio
country: Switzerland
facility: Ospedale Beata Vergine
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thun
country: Switzerland
facility: Regionalspital
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Stefan Aebi, MD
role: STUDY_CHAIR
affiliation: European Institute of Oncology
name: Andrea Decensi, MD
role: STUDY_CHAIR
References:
citation: Decensi A, Sun Z, Guerrieri-Gonzaga A, Thurlimann B, McIntosh C, Tondini C, Monnier A, Campone M, Debled M, Schonenberger A, Zaman K, Johansson H, Price KN, Gelber RD, Goldhirsch A, Coates AS, Aebi S. Bone mineral density and circulating biomarkers in the BIG 1-98 trial comparing adjuvant letrozole, tamoxifen and their sequences. Breast Cancer Res Treat. 2014 Apr;144(2):321-9. doi: 10.1007/s10549-014-2849-2. Epub 2014 Feb 1.