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Trial registered on ANZCTR


Trial ID
ACTRN12605000216617
Ethics application status
Approved
Date submitted
24/08/2005
Date registered
25/08/2005
Date last updated
5/02/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
ANZ 02P2 / International Breast cancer Intervention Study: IBIS-II (Prevention)
Scientific title
International Breast cancer Intervention Study II (IBIS-II) Prevention Protocol, An international multi-centre study of anastrozole vs placebo in postmenopausal women at increased risk of breast cancer.
Secondary ID [1] 121 0
National Clinical Trials Registry: NCTR581
Universal Trial Number (UTN)
Trial acronym
ANZ 02P2: IBIS-II (Prevention)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Increased breast cancer risk 299 0
Condition category
Condition code
Reproductive Health and Childbirth 339 339 0 0
Menstruation and menopause
Cancer 340 340 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The ANZ 02P2 / IBIS II trial is conducted by the ANZ Breast Cancer Trials Group (ANZ BCTG) as part of a collaborative project of the Breast Cancer Trials Coordinating Subcommittee of Cancer Research UK and intergroup collaboration.

IBIS-II (Prevention) is designed to continue the work started in IBIS-I in determining whether a chemopreventive strategy towards breast cancer is beneficial. IBIS-I investigated the use of tamoxifen as a preventive agent for women with moderate to increased risk of developing breast cancer. IBIS-II (Prevention) will compare anastrozole vs placebo.

IBIS-II (Prevention) is an international multicentre, randomised, placebo-controlled clinical trial of 6,000 postmenopausal women aged between 40 and 70 years who are at increased risk of breast cancer. In general terms increased risk is determined from family history, previous benign disease with evidence of proliferation, mammographic dysplasia, and nulliparity.

Women will be randomised in a 2-arm design to receive one of the following:

a. Anastrozole 1mg
b. Anastrozole placebo

All treatment will be on a daily basis for 5 years.
Intervention code [1] 237 0
Prevention
Comparator / control treatment
Anastrozole placebo
Control group
Placebo

Outcomes
Primary outcome [1] 395 0
To determine if anastrozole is effective in preventing breast cancer in postmenopausal women at increased risk of the disease.
Timepoint [1] 395 0
The principal analysis for comparing the active treatment to placebo will be performed when 135 cases of breast cancer have been diagnosed in the prevention stratum. Centres participating in the trial will be required to inform the coordinating body (ANZ BCTG) of any breast cancer occurrences for in participants at their centres as soon as they are made aware of this. This information will be passed on to the central coodinating body (Cancer Research UK) who will do the analysis once 135 cases have been recorded worldwide. Centres are required to submit a CRF, pathology reports and parafin slides of all breast tumours which occur on trial.
Primary outcome [2] 396 0
The principal analysis to compare the active treatment to the placebo will be performed when 135 cases of breast cancer have been diagnosed in the prevention stratum.
Timepoint [2] 396 0
The principal analysis for comparing the active treatment to placebo will be performed when 135 cases of breast cancer have been diagnosed in the prevention stratum. Centres participating in the trial will be required to inform the coordinating body (ANZ BCTG) of any breast cancer occurrences for in participants at their centres as soon as they are made aware of this. This information will be passed on to the central coodinating body (Cancer Research UK) who will do the analysis once 135 cases have been recorded worldwide. Centres are required to submit a CRF, pathology reports and parafin slides of all breast tumours which occur on trial.
Secondary outcome [1] 864 0
To examine the role of anastrozole in preventing oestrogen receptor positive breast cancer.
Timepoint [1] 864 0
The power to detect this within 10 years is marginal and an overview of other similar trials will be needed to obtain clear results on this question.
Secondary outcome [2] 865 0
To examine the effect of anastrozole on breast cancer mortality and on other cancers, cardiovascular disease, fracture rates, and non-breast cancer deaths.
Timepoint [2] 865 0
During the 5-year period of active follow-up and for a further 5 years, other serious medical conditions will be recorded including myocardial infarction, thromboembolic events (superficial and deep), other cardiovascular events, osteoporosis, fractures, other cancers and eye problems. Details of side effects/illnesses will be recorded on CRFs at baseline, 6 months, and then yearly until 5 years of treatment is completed. If the participant ceases treatment before 5 years this information will be collected by annual questionnaire until 10 years after randomisation. After 5 years of treatment annual questionnaires will also be used to collect this information for another 5 years. Blood samples will be collected at baseline, 1 and 5 years. DXA scans and spinal x-rays are required some time in the 2 years prior to randomisation and if the participant has osteoporosis, or is on the bone sub-study, they are required every 2 years or at 1,3 and 5 years respectively. Mammograms are required at baseline (or in the 12 months prior) and yearly thereafter while on trial. Pathology specimens (parafin blocks) are required at baseline for those entereing the trial after DCIS treated by mastectomy. They are also required for any breast, endometrial or ovarian tumours which develop on trial.
Secondary outcome [3] 866 0
To examine tolerability and acceptability of side effects experienced by women on the trial.
Timepoint [3] 866 0
During the 5-year period of active follow-up and for a further 5 years, other serious medical conditions will be recorded including myocardial infarction, thromboembolic events (superficial and deep), other cardiovascular events, osteoporosis, fractures, other cancers and eye problems.Details of side effects/illnesses will be recorded on CRFs at baseline, 6 months, and then yearly until 5 years of treatment is completed. If the participant ceases treatment before 5 years this information will be collected by annual questionnaire until 10 years after randomisation. After 5 years of treatment annual questionnaires will also be used to collect this information for another 5 years. Blood samples will be collected at baseline, 1 and 5 years. DXA scans and spinal x-rays are required some time in the 2 years prior to randomisation and if the participant has osteoporosis, or is on the bone sub-study, they are required every 2 years or at 1,3 and 5 years respectively. Mammograms are required at baseline (or in the 12 months prior) and yearly thereafter while on trial. Pathology specimens (parafin blocks) are required at baseline for those entereing the trial after DCIS treated by mastectomy. They are also required for any breast, endometrial or ovarian tumours which develop on trial.

Eligibility
Key inclusion criteria
1. All women must be postmenopausal and between the ages of 40-70. 2. Hormone replacement therapy must be stopped at least 8 weeks prior to randomisation.3. A bilateral mammogram, or unilateral mammogram for women who have had a mastectomy for prior DCIS, must have been taken within the last year and must not show any evidence of breast cancer. 4. A baseline bone mineral density scan within the last two years (DXA either of hip, lumbar spine, femoral neck or forearm) will be required for all women. A spinal x-ray within the last two years to assess low trauma vertebral fractures will also be required.5. Fully informed signed consent must be provided. 6. Fulfill at least one other age-dependent entry criteria which reflects increasing baseline risk with age.7. Must be accessible for treatment and follow up via a participating institution.
8. Participants from the IBIS-I clinical trial who have been off trial therapy for at least 5 years, are eligible to join the IBIS-II clinical trial provided they comply with all other eligibility criteria
Minimum age
40 Years
Maximum age
70 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Premenopausal women.2. Any previous cancer in the last 5 years (except non-melanoma skin cancer, unilateral DCIS treated by mastectomy or in situ cancer of the cervix).3. Current or previous tamoxifen or raloxifene or other SERMs use for more than 3 months. Participants from the IBIS-I clinical trial who have been off trial therapy for at least 5 years are excepted.4. Intention to continue to use oestrogen-based hormone replacement therapy.5. Women who have either had a prophylactic mastectomy or are planning to have this procedure. 6. Women with a T-score of less than -4 or more than 2 low trauma vertebral fractures are not eligible. Women with a T-score of greater than -4 or 2 or less vertebral fractures are eligible if they agree to join the bone substudy or take bisphosphonates and have regular DXA scans. 7. Any severe concomitant disease that would, in the opinion of the investigator, place the woman at unusual risk or confound the results of the trial.8. Life expectancy of less than 10 years or other medical condition that would significantly interfere with the ability to accept the chemopreventive treatments.9. Psychologically and physically unsuitable for five years anti-oestrogen therapy.10. Treatment with non-approved or experimental drug within 3 months before randomisation.11. Women with gluten-sensitivity

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, University of Sydney will provide a central randomisation service by fax for all Australian and New Zealand institutions. At the time of study entry all 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)
NSW,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 5805 0
New Zealand
State/province [1] 5805 0

Funding & Sponsors
Funding source category [1] 400 0
Self funded/Unfunded
Name [1] 400 0
Australia and New Zealand Breast Cancer Trials Group
Address [1] 400 0
PO Box 155
Hunter Region Mail Centre NSW 2310
Country [1] 400 0
Australia
Funding source category [2] 401 0
Government body
Name [2] 401 0
NHMRC Project Grant 2004-2008
Address [2] 401 0
NHMRC CLINICAL TRIALS CENTRE
Level 5 Building F
Mallett Street
CAMPERDOWN NSW 2050
Country [2] 401 0
Australia
Funding source category [3] 402 0
Charities/Societies/Foundations
Name [3] 402 0
Cancer Research UK
Address [3] 402 0
Cancer Research UK Centre for
Epidemiology, Mathematics and Statistics
Wolfson Institute of Preventive Medicine
Charterhouse Square
London EC1M 6BQ
United Kingdom
Country [3] 402 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] 325 0
University
Name [1] 325 0
Queen Mary University of London
Address [1] 325 0
Mile End, London, E1 4NS, United Kingdom
Country [1] 325 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 1387 0
Newcastle Mater Misericordiae Hospital
Ethics committee address [1] 1387 0
Newcastle, NSW
Ethics committee country [1] 1387 0
Australia
Date submitted for ethics approval [1] 1387 0
Approval date [1] 1387 0
Ethics approval number [1] 1387 0
Ethics committee name [2] 1388 0
Riverina Cancer Care Centre
Ethics committee address [2] 1388 0
Wagga Wagga,NSW
Ethics committee country [2] 1388 0
Australia
Date submitted for ethics approval [2] 1388 0
Approval date [2] 1388 0
Ethics approval number [2] 1388 0

Summary
Brief summary
This study aims to determine whether the drug anastrozole can prevent breast cancer in postmenopausal women at increased risk of the disease.
Who is it for?
You may be eligible join this study if you are a postmenopausal woman aged 40-70 years and are at increased risk of breast cancer. In general terms increased risk is determined from family history, previous benign disease with evidence of proliferation, mammographic dysplasia, and childlessness (nulliparity).
Trial details
Participants in this trial will be randomly (by chance) allocated to one of two groups. Participants in one group will take one 1mg anastrozole tablet daily for 5 years. Participants in the other group will take a placebo (inactive) tablet daily for 5 years. Participants will be regularly assessed over the duration of the trial to determine whether anastrozole is effective in preventing breast cancer in postmenopausal women at increased risk of the disease.
Trial website
www.anzbctg.org
Trial related presentations / publications
Cuzick J, Sestak I, Forbes JF, Dowsett M, Knox J, Cawthorn S, Saunders C, Roche N, Mansel RE, von Minckwitz G, Bonanni B, Palva T, Howell A. Breast cancer prevention using anastrozole in postmenopausal women at high risk. SABCS 2013 2013; Abstract S3-01.


Cuzik J, Sestak I, Forbes JF, Dowsett M, Knox J, Cawthorn S, Saunders C, Roche N, Mansel RE, von Minckwitz G, Bonanni B, Palva T, Howell A, on behalf of the IBIS-II investigators. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. The Lancet 2013; epub 12 December 2013:1-8.

Sestak I, Harvie M, Howell A, Forbes JF, Dowsett M, Cuzick J. Weight change associated with anastrozole and tamoxifen treatment in postmenopausal women with or at high risk of developing breast cancer. Breast Cancer Research and Treatment 2012; 134(2):727-734.

Phillips KA, Ribi K, Fisher R. Do aromatase inhibitors have adverse effects on cognitive function? Breast Cancer Res 2011; 13(1):203.


Juraskova I, Butow P, Smith B, Seccombe M, Coates A, Boyle F, McCarthy N, Reaby L, Forbes JF. Improving informed consent: Evaluating the first decision aid in a clinical trial setting (IBIS-II breast cancer prevention trial). SABCS 2010; Poster 901.

Gao J, Warren R, Warren-Forward H, Forbes JF. Reproducability of visual assessment of mammographic density. Breast Cancer Res Treat 2008; 180:121-127.

Juraskova I, Butow P, Lopez A, Seccombe M, Boyle F, McCarthy N, Forbes JF. Improving informed consent in clinical trials: successful piloting of a decision aid. J Clin Oncol 2007; 25(11):1443-1444.


Juraskova I, Butow P, Lopez AL, Seccombe M, Smith B, Coates A, Boyle F, McCarthy N, Reaby L, Forbes JF. Improving informed consent in clinical trials: a randomised controlled trial of a decision aid for women invited to participate in a breast cancer prevention trial (IBIS-II). SABCS 2007; 4051.


Gao JN, Warren R, Forbes JF, Warren-Forward H, D'Este C. Reproducability of visual assessment of mammographic density. San Antonio Breast Cancer Symp 2006; Poster 5034.


Jenkins V, Atkins L, Ambroisine L, Fleissig A, Fallowfield L, Howell A. Preliminary results from the IBIS II (prevention) cognitive sub-protocol. San Antonio Breast Cancer Symp 2006; Poster 5076.


Singh S, Howell A, Cuzick J. Vit D levels among patients with Arthralgia: results from IBIS-II breast cancer prevention study. San Antonio Breast Cancer Symp 2006; Poster 1068.


Singh S, Richmond B, Howell A, Cuzick J. Effects of anastrozole on cholesterol fractions in postmenopausal women with high risk of breast cancer: results from IBIS-II breast cancer prevention study. San Antonio Breast Cancer Symp 2006; Poster 1055.



Cuzick J. Aromatase inhibitors for breast cancer prevention. J Clin Oncol 2005; 23(8):1636-1643.
Public notes

Contacts
Principal investigator
Name 36337 0
Prof John F Forbes
Address 36337 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 36337 0
Australia
Phone 36337 0
+61 2 4925 5235
Fax 36337 0
Email 36337 0
enquiries@anzbctg.org
Contact person for public queries
Name 9426 0
Prof John F Forbes
Address 9426 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 9426 0
Australia
Phone 9426 0
+61 2 4925 3068
Fax 9426 0
+61 2 49850141
Email 9426 0
enquiries@anzbctg.org
Contact person for scientific queries
Name 354 0
Prof John F Forbes
Address 354 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 354 0
Australia
Phone 354 0
+61 2 4925 3068
Fax 354 0
+61 2 49850141
Email 354 0
enquiries@anzbctg.org