Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00078832




Registration number
NCT00078832
Ethics application status
Date submitted
8/03/2004
Date registered
9/03/2004
Date last updated
6/10/2021

Titles & IDs
Public title
Anastrozole in Preventing Breast Cancer in Postmenopausal Women at Increased Risk of Breast Cancer
Scientific title
International Breast Cancer Intervention Study
Secondary ID [1] 0 0
EU-20227
Secondary ID [2] 0 0
ISRCTN31488319
Universal Trial Number (UTN)
Trial acronym
IBIS II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - anastrozole
Treatment: Drugs - placebo

Experimental: anastrozole - anastrozole 1mg

Placebo Comparator: placebo - anastrozole 1mg PLACEBO


Treatment: Drugs: anastrozole
aromatase inhibitor

Treatment: Drugs: placebo
Arimidex placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years
Timepoint [1] 0 0
Dec 2013
Secondary outcome [1] 0 0
Breast cancer mortality with median follow-up at 10 years
Timepoint [1] 0 0
Dec 2018

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

- Meets at least 1 of the relative risk factors based on age as follows:

- 45 to 70 years of age:

- First-degree relative who developed breast cancer at = 50 years of age

- First-degree relative who developed bilateral breast cancer

- Two or more first- or second-degree relatives who developed breast cancer or
ovarian cancer

- Participants having both relatives who are second degree and on the
opposite sides of the family must have at least one that was diagnosed
at = 50 years of age

- Nulliparous (or first birth at = 30 years of age) and a first-degree
relative who developed breast cancer

- Benign biopsy with proliferative disease and a first-degree relative who
developed breast cancer

- Mammographic opacity covering at least 50% of the breast in the absence of
hormone replacement therapy within the past 3 months

- 60 to 70 years of age:

- First-degree relative with breast cancer at any age

- Age at menopause = 55 years

- Nulliparous or age at first birth = 30 years

- 40 to 44 years of age:

- Two or more first- or second-degree relatives who developed breast cancer or
ovarian cancer at = 50 years of age

- First-degree relative with bilateral breast cancer who developed the first
breast cancer at = 50 years of age

- Nulliparous (or first birth at = 30 years of age) and a first-degree
relative who developed breast cancer at = 40 years of age

- Benign biopsy with proliferative disease and a first-degree relative who
developed breast cancer at = 40 years of age

- All age groups (40 to 70 ears of age) with a 10-year risk > 5% who do not fit into the
above categories are allowed

- Clearly apparent family history AND/OR other risk factors indicating appropriate
increased risk of breast cancer for age

- The following prior breast conditions are allowed (for all age groups):

- Lobular carcinoma in situ

- Atypical ductal or lobular hyperplasia in a benign lesion

- Ductal carcinoma in-situ (DCIS), diagnosed within the past 6 months, and treated
by mastectomy

- No evidence of breast cancer on mammogram within the past year

- Hormone receptor status:

- For patients with prior DCIS, estrogen- or progesterone-receptor status must have
been positive

- Must have had greater than or equal to 5% positive cells

PATIENT CHARACTERISTICS:

Age

- 40 to 70

Sex

- Female

Menopausal status

- Postmenopausal, defined as at least 1 of the following:

- Over 60 years of age

- Bilateral oophorectomy

- = 60 years of age with a uterus and amenorrhea for at least 12 months

- = 60 years of age without a uterus and with follicle-stimulating hormone levels >
30 IU/L

Performance status

- Not specified

Life expectancy

- At least 10 years

Hematopoietic

- Not specified

Hepatic

- Not specified

Renal

- Not specified

Other

- Psychologically and physically suitable to receive 5 years of anti-estrogen therapy

- No cancer within the past 5 years except non-melanoma skin cancer or carcinoma in situ
of the cervix

- No evidence of osteoporosis or fragility fractures within the spine

- Participants with a T-score > minus 4 and no more than 2 fragility fractures are
allowed

- No concurrent severe disease that would place the participant at unusual risk or
confound the results of the study

- No other medical condition that would preclude the ability to receive the study
treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- Not specified

Endocrine therapy

- No prior tamoxifen, raloxifene, or other selective estrogen receptor modulator (SERM)
use for more than 6 months in duration unless an IBIS-I participant (must have been
off trial therapy for at least 5 years.

- No concurrent tamoxifen, raloxifene, or other SERM

- No concurrent estrogen-based hormone replacement therapy

- No concurrent systemic estrogen replacement therapy, including vaginal estrogen
preparations

Radiotherapy

- Not specified

Surgery

- See Disease Characteristics

- No prior prophylactic mastectomy

- No concurrent prophylactic mastectomy

Other

- More than 6 months since prior investigational drugs
Minimum age
40 Years
Maximum age
70 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/05/2021
Sample size
Target
Accrual to date
Final
3864
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Newcastle Mater Hospital - Newcastle
Recruitment postcode(s) [1] 0 0
2310 - Newcastle
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Leuven
Country [2] 0 0
Chile
State/province [2] 0 0
Santiago
Country [3] 0 0
Denmark
State/province [3] 0 0
Horsholm
Country [4] 0 0
Finland
State/province [4] 0 0
Tampere
Country [5] 0 0
Germany
State/province [5] 0 0
Frankfurt
Country [6] 0 0
Hungary
State/province [6] 0 0
Szeged
Country [7] 0 0
Ireland
State/province [7] 0 0
Beaumont
Country [8] 0 0
Ireland
State/province [8] 0 0
Tallaght
Country [9] 0 0
Ireland
State/province [9] 0 0
Cork
Country [10] 0 0
Ireland
State/province [10] 0 0
Dublin
Country [11] 0 0
Ireland
State/province [11] 0 0
Galway
Country [12] 0 0
Ireland
State/province [12] 0 0
Limerick
Country [13] 0 0
Ireland
State/province [13] 0 0
Sligo
Country [14] 0 0
Italy
State/province [14] 0 0
Milan
Country [15] 0 0
Malta
State/province [15] 0 0
Floriana
Country [16] 0 0
Portugal
State/province [16] 0 0
Lisbon
Country [17] 0 0
Switzerland
State/province [17] 0 0
Bern
Country [18] 0 0
Switzerland
State/province [18] 0 0
Geneva
Country [19] 0 0
Switzerland
State/province [19] 0 0
Mendrisio
Country [20] 0 0
Switzerland
State/province [20] 0 0
St. Gallen
Country [21] 0 0
Switzerland
State/province [21] 0 0
Thun
Country [22] 0 0
Turkey
State/province [22] 0 0
Istanbul
Country [23] 0 0
United Kingdom
State/province [23] 0 0
England
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Northern Ireland
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Scotland
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Wales
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Aberdeen
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Grantham
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Huddersfield
Country [30] 0 0
United Kingdom
State/province [30] 0 0
London
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Manchester
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Middlesex
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Newcastle
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Nottingham
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Oldham
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Plymouth
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Sheffield
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Southampton
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Stafford
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Truro
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Wishaw
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Yeovil

Funding & Sponsors
Primary sponsor type
Other
Name
Queen Mary University of London
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the
development of cancer. Anastrozole may be effective in preventing breast cancer.

PURPOSE: This randomized clinical trial is studying how well anastrozole works in preventing
breast cancer in postmenopausal women who are at increased risk for the disease.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00078832
Trial related presentations / publications
Sestak I, Singh S, Cuzick J, Blake GM, Patel R, Gossiel F, Coleman R, Dowsett M, Forbes JF, Howell A, Eastell R. Changes in bone mineral density at 3 years in postmenopausal women receiving anastrozole and risedronate in the IBIS-II bone substudy: an international, double-blind, randomised, placebo-controlled trial. Lancet Oncol. 2014 Dec;15(13):1460-1468. doi: 10.1016/S1470-2045(14)71035-6. Epub 2014 Nov 11. Erratum In: Lancet Oncol. 2014 Dec;15(13):e587. Lancet Oncol. 2014 Dec;15(13):e587.
Jenkins VA, Ambroisine LM, Atkins L, Cuzick J, Howell A, Fallowfield LJ. Effects of anastrozole on cognitive performance in postmenopausal women: a randomised, double-blind chemoprevention trial (IBIS II). Lancet Oncol. 2008 Oct;9(10):953-61. doi: 10.1016/S1470-2045(08)70207-9. Epub 2008 Sep 1.
Sestak I, Smith SG, Howell A, Forbes JF, Cuzick J. Early participant-reported symptoms as predictors of adherence to anastrozole in the International Breast Cancer Intervention Studies II. Ann Oncol. 2018 Feb 1;29(2):504-509. doi: 10.1093/annonc/mdx713.
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; IBIS-II investigators. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet. 2014 Mar 22;383(9922):1041-8. doi: 10.1016/S0140-6736(13)62292-8. Epub 2013 Dec 12. Erratum In: Lancet. 2014 Mar 22;383(9922):1040. Lancet. 2017 Mar 11;389(10073):1010.
Public notes

Contacts
Principal investigator
Name 0 0
Jack Cuzick, PhD
Address 0 0
Queen Mary University of London
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00078832