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

NCT00369850 | Completed Phase 3 DMC

• 5 other identifiers: CDR0000482381IBCSG-18-98-BSEU-20623IBCSG-1-98-BSNOVARTIS-2026703019
• Study Type: interventional
• Target: 458
• Locations: 8 countries
• Sites: 16

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.

Conditions

Breast Cancer; Osteoporosis

Keywords

osteoporosis; stage I breast cancer; stage II breast cancer; stage IIIA breast cancer

Outcome Measures

Primary Outcomes (5)

• 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

• Recovery of BMD at 1 year after the completion of treatment on protocol IBCSG-1-98

  6 years after randomisation to BIG 1-98

• Proportion of patients with BMD below the absolute threshold value for osteoporosis

  5 years after randomisation to BIG 1-98

• 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

• 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

Study Arms (4)

Tamoxifen for 5 years

EXPERIMENTAL

Patients treated with tamoxifen for 5 years after randomisation.

Other: laboratory biomarker analysis; Procedure: Dual energy X-ray absorptiometry (DEXA); Procedure: Spine X-ray

Letrozole for 5 years

EXPERIMENTAL

Patients treated with letrozole for 5 years after randomisation.

Other: laboratory biomarker analysis; Procedure: Dual energy X-ray absorptiometry (DEXA); Procedure: Spine X-ray

Tamoxifen 2 years plus letrozole 3 years

EXPERIMENTAL

Patients treated with tamoxifen for 2 years and afterwards with letrozole for 3 years.

Other: laboratory biomarker analysis; Procedure: Dual energy X-ray absorptiometry (DEXA); Procedure: Spine X-ray

Letrozole 2 years plus tamoxifen 3 years

EXPERIMENTAL

Patients treated with letrozole for 2 years and afterwards with tamoxifen for 3 years.

Other: laboratory biomarker analysis; Procedure: Dual energy X-ray absorptiometry (DEXA); Procedure: Spine X-ray

Interventions

laboratory biomarker analysis OTHER

Biomarkers (C-telopeptide, osteocalcin and skeletal alkaline phosphatase) will be assessed in serum.

Letrozole 2 years plus tamoxifen 3 years; Letrozole for 5 years; Tamoxifen 2 years plus letrozole 3 years; Tamoxifen for 5 years

Dual energy X-ray absorptiometry (DEXA) PROCEDURE

Mone mineral density measurements of L2-L4 and hip will be performed using DEXA.

Letrozole 2 years plus tamoxifen 3 years; Letrozole for 5 years; Tamoxifen 2 years plus letrozole 3 years; Tamoxifen for 5 years

Spine X-ray PROCEDURE

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

Letrozole 2 years plus tamoxifen 3 years; Letrozole for 5 years; Tamoxifen 2 years plus letrozole 3 years; Tamoxifen for 5 years

Eligibility Criteria

• Age: 30 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead

Study Sites (16)

Institute of Oncology at Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centro di Riferimento Oncologico - Aviano

Aviano, 33081, Italy

Location

Ospedali Riuniti di Bergamo

Bergamo, 24100, Italy

Location

European Institute of Oncology

Milan, 20141, Italy

Location

Dunedin Hospital

Dunedin, New Zealand

Location

Instituto Nacional de Enfermedades Neoplasicas

Lima, 34, Peru

Location

Groote Schuur Hospital

Cape Town, 7925, South Africa

Location

Hospital Ruber Internacional

Madrid, 28034, Spain

Location

Kantonspital Aarau

Aarau, CH-5001, Switzerland

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Ospedale Beata Vergine

Mendrisio, CH-6850, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 24487691 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Osteoporosis

Interventions

Absorptiometry, Photon

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Stefan Aebi, MD

  Insel Gruppe AG, University Hospital Bern

  STUDY CHAIR

• Andrea Decensi, MD

  European Institute of Oncology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2006
• First Posted: August 29, 2006
• Study Start: May 1, 2004
• Primary Completion: May 1, 2008
• Study Completion: January 1, 2012
• Last Updated: July 27, 2012

Record last verified: 2012-07

Locations

ES (1); CH (6); IT (3); NZ (1); FR (1); PE (1); ZA (1); AU (2)