Trial registered on ANZCTR


Trial ID
ACTRN12605000282684
Ethics application status
Approved
Date submitted
24/08/2005
Date registered
2/09/2005
Date last updated
5/02/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
ANZ 02P2 / International Breast cancer Intervention Study: IBIS-II DCIS
Scientific title
International Breast cancer Intervention Study II (IBIS-II) DCIS Protocol, An international multi-centre study of tamoxifen vs anastrozole in postmenopausal women with hormone sensitive Ductal Carcinoma In Situ (DCIS)
Secondary ID [1] 135 0
National Clinical Trials Registry: NCTR582
Universal Trial Number (UTN)
Trial acronym
ANZ 02P2 / IBIS-II (DCIS)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Increased breast cancer risk 370 0
Condition category
Condition code
Cancer 435 435 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Anastrozole 1 mg + Tamoxifen placebo (lactose pill). All treatment will be on a daily basis for 5 years and all women will take 2 tablets/day orally.
Intervention code [1] 238 0
Prevention
Comparator / control treatment
Tamoxifen 20 mg and anastrozole placebo (lactose pill). All treatment will be on a daily basis for 5 years and all women will take 2 tablets/day orally.
Control group
Active

Outcomes
Primary outcome [1] 496 0
To determine if anastrozole is at least as effective as tamoxifen in local control and prevention of contralateral disease in women with unilateral locally excised ER and/or PgR +ve DCIS.
Timepoint [1] 496 0
The expected number of new cancers in each arm will be analysed after 5 years of median follow up
Primary outcome [2] 497 0
To compare side effect profiles of tamoxifen and anastrozole.
Timepoint [2] 497 0
The expected number of new cancers in each arm will be analysed after 5 years of median follow up
Secondary outcome [1] 1065 0
To compare the effectiveness of tamoxifen and anastrozole according to the receptor status of the primary or recurrent cancer.
Timepoint [1] 1065 0
The expected number of new cancers in each arm will be analysed after 5 years of median follow up
Secondary outcome [2] 1066 0
To examine the rate of breast cancer recurrence and new contralateral tumours after cessation of tamoxifen or anastrozole.
Timepoint [2] 1066 0
The expected number of new cancers in each arm will be analysed after 5 years of median follow up
Secondary outcome [3] 1067 0
To examine the effect of tamoxifen vs anastrozole on breast cancer mortality.
Timepoint [3] 1067 0
It is recognised that breast cancer mortality is an important secondary endpoint and this will also be analysed. The death of a IBIS II participant whilst on trial will be recorded on a death form. This data will be submitted to and compiled by the central coordinating centre in London UK (CRUK). The significance of this data will be determined at some time after 10 years worth of data has been collected and will need to involve an overview of similar trials to get clear results on this question. No definite time line for this analysis has been set.
Secondary outcome [4] 1068 0
To examine the effect of tamoxifen and anastrozole on other cancers, cardiovascular disease, fracture rates, and non-breast cancer deaths.
Timepoint [4] 1068 0
During the period of active follow-up (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. Data will be collected using CRFs completed by Principal investigators/data management staff at baseline, 6 months and then yearly until 5 years post randomisation. If the participant ceases treatment before 5 years they will be followed up using an annual questionnaire. An annual questionnaire will also be used to follow up women for another 5 years after they cease their 5 years of treatment. Mammograms will be required annually. Blood tests are required at baseline, 1 and 5 years. A DXA and spinal x-ray are required to have been taken within 2 years of entry to the study and if the participant has osteoporosis they must have DXA scans every 2 years while on the trial. Samples of the participant's DCIS tumour (parafin blocks) are required for analysis at baseline. Tumour samples (parafin blocks) will also be required for any subsequent tumours which develop while on trial in the breast, endometrium or ovaries.
Secondary outcome [5] 1069 0
To examine tolerability and acceptability of side effects experienced by women on the trial.
Timepoint [5] 1069 0
During the period of active follow-up (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.Data will be collected using CRFs completed by Principal investigators/data management staff at baseline, 6 months and then yearly until 5 years post randomisation. If the participant ceases treatment before 5 years they will be followed up using an annual questionnaire. An annual questionnaire will also be used to follow up women for another 5 years after they cease their 5 years of treatment. Mammograms will be required annually. Blood tests are required at baseline, 1 and 5 years. A DXA and spinal x-ray are required to have been taken within 2 years of entry to the study and if the participant has osteoporosis they must have DXA scans every 2 years while on the trial. Samples of the participant's DCIS tumour (parafin blocks) are required for analysis at baseline. Tumour samples (parafin blocks) will also be required for any subsequent tumours which develop while on trial in the breast, endometrium or ovaries.

Eligibility
Key inclusion criteria
1. All women must be postmenopausal. 2. Hormone replacement therapy must have stopped at least 8 weeks prior to randomisation.3. Locally excised unilateral DCIS diagnosed within the last 6 months. Oestrogen receptor and/or progesterone receptor (ER and/or PgR) status of the DCIS must be known and greater than 5% positive cells.4. A baseline bone mineral density scan within the last 2 years (DXA either of hip, lumbar spine or forearm) will be required for all women. A spinal x-ray within the last 2 years to rule out low trauma vertebral fractures will also be required.5. A bilateral mammogram must have been taken within the last year.6. Fully informed consent must be provided.7. Women treated by mastectomy will not be eligible for this trial, but may enter the parallel IBIS II (Prevention) trial.8. Must be accessible for treatment and follow up via a participating institution.
9. 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 (except non-melanoma skin cancer or in situ cancer of the cervix) in the past 5 years.3. Bilateral DCIS.4. Current treatment with anti-coagulants.5. Previous deep vein thrombosis or pulmonary embolus.6. Previous transient ischaemic attack (TIA) or cerebrovascular accident (CVA, stroke).7. 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.8. Intention to continue to use oestrogen-based hormone replacement therapy.9. Women who have either had a prophylactic mastectomy or are planning to have this procedure. 10. Any woman with unexplained postmenopausal bleeding. 11. Evidence of osteoporosis or low trauma vertebral fractures within the spine. 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.12. 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.13. Life expectancy of less than 10 years or other medical condition which would significantly interfere with the ability to accept the chemopreventive treatments.14. Psychologically and physically unsuitable for five years anti-oestrogen therapy.15. Treatment with non-approved or experimental drug during the 3 months before randomisation.16. 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,VIC,QLD,SA,WA

Funding & Sponsors
Funding source category [1] 485 0
Self funded/Unfunded
Name [1] 485 0
ANZ Breast Cancer Trials Group
Address [1] 485 0
PO Box 155
Hunter Region Mail Centre NSW 2310
Country [1] 485 0
Australia
Funding source category [2] 486 0
Government body
Name [2] 486 0
NHMRC Project Grant 2004-2008
Address [2] 486 0
Address not applicable
Country [2] 486 0
Australia
Funding source category [3] 487 0
Charities/Societies/Foundations
Name [3] 487 0
Cancer Research UK
Address [3] 487 0
Cancer Research UK
Department of Epidemiology, Mathematics and Statistics
Wolfson Institute of Preventive Medicine
Charterhouse Square
London
EC1M 6BQ
UNITED KINGDOM
Country [3] 487 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] 392 0
University
Name [1] 392 0
Queen Mary University of London
Address [1] 392 0
Queen Mary, University of London, Mile End Road, London E1 4NS
Country [1] 392 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 1465 0
Newcastle Mater Misericordiae Hospital
Ethics committee address [1] 1465 0
Newcastle, NSW
Ethics committee country [1] 1465 0
Australia
Date submitted for ethics approval [1] 1465 0
Approval date [1] 1465 0
Ethics approval number [1] 1465 0
Ethics committee name [2] 1466 0
Riverina Cancer Centre
Ethics committee address [2] 1466 0
Wagga Wagga, NSW
Ethics committee country [2] 1466 0
Australia
Date submitted for ethics approval [2] 1466 0
Approval date [2] 1466 0
Ethics approval number [2] 1466 0

Summary
Brief summary
Phase 3

This study is comparing the effectiveness of the drugs tamoxifen versus anastrozole in postmenopausal women with hormone sensitive ductal carcinoma in situ (DCIS).
This is an ANZ 02P2/ International Breast Cancer Intervention Study: IBIS-II DCIS.

Who is it for?
You can join this trial if:
You are a postmenopausal woman aged between 40 and 70 years. You must have had DCIS diagnosed in one breast within the last 6 months. The DCIS must have been hormone sensitive and have been locally removed (i.e.not by mastectomy).
Trial details
Participants will be randomly divided into two groups. One group receives tamoxifen plus a non-active compound in place of anastrozole. The other group receives anastrozole plus a non-active compound in place of tamoxifen. These are taken orally, every day for 5 years. The study aims to compare how effective the two drugs are in preventing and controlling locally any subsequent disease, in the same or the other breast.

DCIS has the potential to develop into breast cancer which can spread to other places in the body. Both tamoxifen and anastrozole lower levels of the hormone oestrogen in the body and are used in women already diagnosed with breast cancer. Tamoxifen is used in some women with DCIS for the prevention of breast cancer. This trial is looking at whether anastrozole is as effective as tamoxifen in preventing further DCIS and breast cancer.
Trial website
www.anzbctg.org
Trial related presentations / publications
Juraskov I, Butow P, Lopez A, Seccombe M, Coates A, Boyle F, McCarthy N, Reaby L, Forbes JF. Improving informed consent: pilot of a decision aid for women invited to participate in a breast cancer prevention trial (IBIS-II DCIS). Health Expectations 2008; 11:252-262
Public notes

Contacts
Principal investigator
Name 35626 0
Prof John F Forbes
Address 35626 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 35626 0
Australia
Phone 35626 0
+61 2 4925 5235
Fax 35626 0
Email 35626 0
enquiries@anzbctg.org
Contact person for public queries
Name 9427 0
Prof John F Forbes
Address 9427 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 9427 0
Australia
Phone 9427 0
+61 2 4925 5235
Fax 9427 0
+61 2 49851041
Email 9427 0
enquiries@anzbctg.org
Contact person for scientific queries
Name 355 0
Prof John F Forbes
Address 355 0
ANZBCTG
PO Box 283
The Junction NSW 2291
Country 355 0
Australia
Phone 355 0
+61 2 4925 5235
Fax 355 0
+61 2 49601539
Email 355 0
enquiries@anzbctg.org