Trial registered on ANZCTR


Trial ID
ACTRN12605000222640
Ethics application status
Approved
Date submitted
24/08/2005
Date registered
26/08/2005
Date last updated
5/02/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
ANZ 02P2 / International Breast cancer Intervention Study: IBIS-II Bone Sub-Protocol
Scientific title
International Breast cancer Intervention Study (IBIS-II) Bone Sub-Protocol, A randomised double-blind trial to assess the effects on bone mineral density and bone biomarkers of anastrozole when used to prevent breast cancer in postmenopausal women
Secondary ID [1] 122 0
National Clinical Trials Registry: NCTR583
Universal Trial Number (UTN)
Trial acronym
ANZ 02P2/IBIS II (Bone)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Increased breast cancer risk 305 0
Osteoporosis 306 0
Osteopenia 307 0
Bone fractures 308 0
Condition category
Condition code
Cancer 348 348 0 0
Breast
Musculoskeletal 349 349 0 0
Osteoporosis
Other 350 350 0 0
Fractures

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The purpose of the bone sub-study is to examine the effect of anastrozole on Bone Mineral Density (BMD) and the risk of developing osteoporosis and fractures. Additionally it will explore the ability of bisphosphonate treatment to reduce the risk in women found to have low bone mineral density at baseline. BMD measurements in the lumbar spine and femoral neck will be performed in 1000 women from the initial entrants of the 6,000 women enrolled in the IBIS-II Prevention Trial (IBIS-II Prevention Protocol). The women will be divided into the following three strata: I. 300 women with T-scores (T) greater than or equal to minus one. These women will be monitored with dual energy X-ray absorptiometry (DXA) scans and recommended to take vitamin D and calcium supplements, but will not initially receive risedronate; II. 400 moderately to severely osteopenic women with T-scores between minus one and minus two point five will be randomised between risedronate sodium (Actonel, 35 mg, orally, once per week) or placebo (lactose pill, orally, once per week) and monitored by DXA scans. Vitamin D and calcium tablets will be recommended to all women; III. 300 Osteoporotic women with T-scores between minus two point five and minus four or up to two low trauma vertebral fractures will be required to take risedronate and be monitored by DXA scans. Risedronate is the bisphosphonate which will be used in the sub-study. The dose is 35 mg oral once a week and treatment will continue for 5 years.
Intervention code [1] 241 0
Prevention
Comparator / control treatment
Placebo
Control group
Placebo

Outcomes
Primary outcome [1] 403 0
To quantify the changes in bone in the spine and femur in postmenopausal women treated with anastrozole compared with the placebo group.
Timepoint [1] 403 0
The primary comparison of Anastrozole compared to Placebo will occur at 3 years. Data for use in this comparison and any subsequent comparisons which may be undertaken will be recorded at baseline, and at the 1, 3, 5 and 7 year visits.
Primary outcome [2] 404 0
To evaluate the impact of bisphosphonate treatment on bone mineral density and bone metabolism in women taking anastrozole, and who are found to be osteoporotic or moderate to severely osteopenic at baseline. Bisphosphonate treatment will be required for women who are found to be osteoporotic at baseline, and will be a randomised option in women who are moderate to severely osteopenic at baseline.
Timepoint [2] 404 0
The primary comparison of Anastrozole compared to Placebo will occur at 3 years.Data for use in this comparison and any subsequent comparisons which may be undertaken will be recorded at baseline, and at the 1, 3, 5 and 7 year visits.
Primary outcome [3] 405 0
To explore the relationship between changes in levels of biochemical markers of bone metabolism with longer term changes in bone mineral density as measured by DXA, related to bone metabolism.
Timepoint [3] 405 0
BMD results at the lumbar spine, total hip and femoral neck sites for the 1, 3, 5 and 7-year follow-up visits will be expressed as the percentage change from baseline and analysed using one-way ANOVA after taking logarithms. Statistical significance of the differences between anastrozole and placebo for the ratio of baseline to follow-up sample (1,3,5 and 7) will be analysed using the Wilcoxon Ranksum Test. Evaluations will be undertaken at each of the follow-up times, but the primary analysis will be based on the 3 year follow-up samples. Statistical significance will be assessed based on a 2-sided p-value of less than 0.05. In addition, a further analysis will be performed on the 7-year data based on the percentage change in BMD from the end of trial medication at Year 5.
Secondary outcome [1] 875 0
Not Applicable
Timepoint [1] 875 0
Not applicable

Eligibility
Key inclusion criteria
Women meeting the entry criteria of the IBIS-II (Prevention) trial will be offered entry into the bone sub-protocol. Women will be selected from the first women randomised into the main trial, and will be enrolled for the sub-protocol subject to: (1) giving informed consent; (2) not being excluded by one or more of the exclusion criteria listed below. Women with T-scores < -2.5 and > -4.0 or 1-2 low trauma vertebral fractures must be treated with risedronate.
Minimum age
40 Years
Maximum age
70 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
criteria: 1. Women with previous bilateral hip fractures or bilateral hip prostheses. This is because reliable DXA scans cannot be performed.2. Women currently with any type of metabolic bone disease including: Paget's disease, osteogenesis imperfecta, disorders of calcium or mineral metabolism, renal calculus, malabsorption, hyper- or hypocalcaemia, hyper- or hypoparathyroidism, hyper- or hypothyroidism (NB: women on stable thyroid replacement therapy can be included provided they are euthyroid as judged by the investigator). Women with previous conditions that have been corrected are eligible.3. Women who have regularly taken any medication affecting bone metabolism within the past 12 months including oestrogen, any bisphosphonate, parathyroid hormone, calcitonin, oral or systemic glucocorticoid.However, women who have been diagnosed as osteoporotic and are currently taking oral bisphosphonate can join stratum III of the bone sub-study providing their T-score is <-2.5 at the time of randomisation (DXA scan done within 3 months of joining the study).4. Women who have a T score less than -4 and/or more than 2 low trauma vertebral fractures.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The ANZ BCTG Statistical Centre at the NHMRC Clinical Trials Centre will provide a central fax randomisation service for all Australian and New Zealand institutions. For stratum II only, at the time of study entry the participants will be allocated a treatment code and study drug will be supplied in accordance with the treatment code.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated stratified blocks.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 408 0
Self funded/Unfunded
Name [1] 408 0
ANZ Breast Cancer Trials Group
Address [1] 408 0
PO Box 155
Hunter Region Mail Centre NSW 2310
Country [1] 408 0
Australia
Funding source category [2] 409 0
Government body
Name [2] 409 0
NHMRC Project Grant 2004-2008
Address [2] 409 0
NHMRC CLINICAL TRIALS CENTRE
Level 5 Building F
Mallett Street
CAMPERDOWN NSW 2050
Country [2] 409 0
Australia
Funding source category [3] 410 0
Charities/Societies/Foundations
Name [3] 410 0
Cancer Research UK
Address [3] 410 0
Cancer Research UK Centre for
Epidemiology, Mathematics and Statistics
Wolfson Institute of Preventive Medicine
Charterhouse Square
London EC1M 6BQ
United Kingdom
Country [3] 410 0
United Kingdom
Primary sponsor type
Other Collaborative groups
Name
Australia and New Zealand Breast Cancer Trials Group
Address
PO Box 155
Hunter Region Mail Centre NSW 2310
Country
Australia
Secondary sponsor category [1] 331 0
University
Name [1] 331 0
Queen Mary University of London
Address [1] 331 0
Mile End, London, E1 4NS, United Kingdom
Country [1] 331 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 1391 0
Newcastle Mater Misericordiae Hospital
Ethics committee address [1] 1391 0
Newcastle,NSW
Ethics committee country [1] 1391 0
Australia
Date submitted for ethics approval [1] 1391 0
Approval date [1] 1391 0
Ethics approval number [1] 1391 0

Summary
Brief summary
Phase 3

This sub-study is assessing the effects of the drug anastrozole on bone mineral density and other indicators on bone strength, when this drug is used to prevent breast cancer in postmenopausal women.
This is an ANZ02P2/International Breast cancer Intervention Study: IBIS II Bone Sub-Protocol.

Who is it for?
You can join this trial if:
You are joining the ANZ02P2 International Breast cancer Intervention Study: IBIS II (Prevention).You must not have not previously have had bilateral hip fractures or bilateral hip prostheses. You must not have a metabolic bone disease. You can not have regularly taken any medication affecting bone metabolism within the past 12 months unless you have been diagnosed as osteoporotic and are currently taking oral bisphosphonate (a bone strengthening drug).

Trial details
Participants will be divided into three groups based on the results of their baseline bone mineral density scans. Group 1 will comprise of participants with normal bone density. It will be recommended that these participants take calcium and vitamin D supplements. Group 2 will comprise of participants with osteopaenia (or reduced bone mineral density). These participants will be divided into two groups. One group will take the drug risedronate orally once a week for 5 years while the other group takes an inactive compound. It will be recommended that these participants also take calcium and vitamin D supplements. Group 3 consists of participants diagnosed with osteoporosis (low bone mineral density). These participants will take risedronate orally once a week for 5 years. All women in this sub-study (Groups 1, 2 and 3) will be monitored with bone mineral density scans.

Risedronate is a type of drug called a bisphosphonate which acts to increase bone mass and strength.
Trial website
www.anzbctg.org
www.ibis-trials.org
Trial related presentations / publications
Singh S, Cuzick J, Edwards R, Blake G, Truscott J, Coleman J, Eastell R, Howell A. Effect of anastrozole on bone mineral density after one year of treatment: results from bone sub-study of the International Breast Cancer Intervention Study (IBIS-II). San Antonio Breast Cancer Symposium 2007; 28.

Singh S, Cuzick J, Blake GM, Mesher D, Patel R, Truscott J, Coleman R, Howell A, Forbes J, Eastell R. One year effect of anastrozole and risendronate on bone mineral density: First results from the IBIS-II bone sub-study. Bone 2011; 48(1):S24
Public notes

Contacts
Principal investigator
Name 35283 0
Prof John F Forbes
Address 35283 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 35283 0
Australia
Phone 35283 0
+61 2 4925 5235
Fax 35283 0
Email 35283 0
enquiries@anzbctg.org
Contact person for public queries
Name 9430 0
Prof John F Forbes
Address 9430 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 9430 0
Australia
Phone 9430 0
+61 2 4925 3068
Fax 9430 0
+61 2 49850141
Email 9430 0
enquiries@anzbctg.org
Contact person for scientific queries
Name 358 0
Prof John F Forbes
Address 358 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 358 0
Australia
Phone 358 0
+61 2 4925 3068
Fax 358 0
+61 2 4985 0141
Email 358 0
enquiries@anzbctg.org.au