Breast CancerPhase 3IBIS IINCT00078832
Anastrozole in Preventing Breast Cancer in Postmenopausal Women at Increased Risk of Breast Cancer
A Phase 3 study testing anastrozole in people with Breast Cancer, run by Queen Mary University of London at 74 sites in 14 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer
- What is being tested?
- anastrozole
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3,864 participants
- Where
- 74 sitesin 14 countries
- Study dates
- Sep 2003to 31 May 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
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
Trial locations and contacts
74 sites in 14 countries.
74 sites in 14 countries
United Kingdom48 sites
Aberdeen Royal Infirmary
Aberdeen, AB25 2ZA
Tameside General Hospital
Ashton-under-Lyne, England, OL6 9RW
Centre for Cancer Research and Cell Biology at Queen's University Belfast
Belfast, Northern Ireland, BT9 7AB
Royal Bolton Hospital
Bolton, England, BL4 0JR
Royal Bournemouth Hospital
Bournemouth, England, BH7 7DW
St. Luke's Hospital
Bradford, England, BD5 0NA
Sussex Cancer Centre at Royal Sussex County Hospital
Brighton, England, BN2 5BE
Frenchay Hospital
Bristol, England, BS16 1LE
Bristol Royal Infirmary
Bristol, England, BS2 8HW
Queen's Hospital
Burton-on-Trent, England, DE13 0RB
University Hospital of Wales
Cardiff, Wales, CF14 4XW
Broomfield Hospital
Chelmsford, England, CM1 7ET
Gloucestershire Oncology Centre at Cheltenham General Hospital
Cheltenham, England, GL53 7AN
Countess of Chester Hospital
Chester, England, CH2 1UL
Essex County Hospital
Colchester, England, C03 3NB
Royal Derby Hospital
Derby, England, DE1 2QY
Ninewells Hospital
Dundee, Scotland, DD1 9SY
Edinburgh Cancer Centre at Western General Hospital
Edinburgh, Scotland, EH4 2XU
Saint Margaret's Hospital,
Epping, England, CM16 6TN
Royal Devon and Exeter Hospital
Exeter, England, EX2 5DW
Frimley Park Hospital
Frimley, England, GU16 7UJ
Lincoln County Hospital
Grantham, LN2 5QY
Conquest Hospital
Hastings, England, TN37 7RD
Calderdale Royal Hospital
Huddersfield, HX3 0PW
Castle Hill Hospital
Hull, England, HU16 5JQ
Airedale General Hospital
Keighley, England, BD20 6TD
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, LS9 7TF
Lincoln County Hospital
Lincoln, England, LN2 5QY
Royal Liverpool University Hospital
Liverpool, England, L7 8XP
Saint Bartholomew's Hospital
London, England, EC1A 7BE
Guy's Hospital
London, England, SE1 9RT
Royal Marsden - London
London, England, SW3 6JJ
Royal Free and UCL Medical School
London, N19 5LW
Macclesfield District General Hospital
Macclesfield, England, SK10 3BL
Paterson Institute for Cancer Research
Manchester, M20 4BX
Northwick Park Hospital
Middlesex, HA1 3UJ
School of Surgical & Reproductive Sciences
Newcastle, NE2 4HH
Nottingham University Hospitals NHS Trust
Nottingham, NG5 1PB
Department of General Surgery Pennine Acute Hospitals NHS Trust
Oldham, OL1 2JH
Derriford Hospital
Plymouth, PL6 8DH
Cancer Clinical Trials Centre
Sheffield, S10 2SJ
Weston Park Hospital, Cancer Clinical Trials Centre, Department of Clinical Oncology
Sheffield, S10 2SJ
Princess Anne Hospital
Southampton, SO16 5YA
Mid Staffordshire NHS Foundation Trust
Stafford, ST16 3SA
Singleton Hospital
Swansea, Wales, SA2 8QA
Treliske Royal Cornwall Hospital
Truro, TR1 3LJ
Wishaw General Hospital
Wishaw, ML2 0DP
Yeovil District Hospital
Yeovil, BA21 4AT
Ireland9 sites
Cork University Hospital
Cork
South Infirmary Victoria Hospital
Cork
Beaumont Hospital
Dublin, Beaumont, 9
Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
Dublin, Tallaght, 24
St. Vincent's University Hospital
Dublin, 4
St. James's Hospital
Dublin, 8
University College Hospital
Galway
Mid-Western Cancer Centre at Mid-Western Regional Hospital
Limerick, 0009
Sligo General Hospital
Sligo
Switzerland6 sites
Inselspital Bern
Bern, CH-3010
Oncocare Sonnenhof-Klinik Engeriedspital
Bern, CH-3012
Hopital Cantonal Universitaire de Geneve
Geneva, CH-1211
Ospedale Beata Vergine
Mendrisio, CH-6850
Tumor Zentrum ZeTup St. Gallen und Chur
Sankt Gallen, CH-9006
Regionalspital
Thun, 3600
Portugal1 site
Instituto Portugues De Oncologia, Gabinete De Estudos Clinicos
Lisbon, 1099-023
Turkey (Türkiye)1 site
Ortaklar cad Pehlivan sok, Basak koviah ap.
Istanbul
About this study
Official title: International Breast Cancer Intervention Study
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.
Read the detailed description
OBJECTIVES:
Primary
- Determine the effectiveness of anastrozole in preventing breast cancer in postmenopausal women at increased risk for the disease.
Secondary
- Determine the role of this drug in preventing estrogen receptor-positive breast cancer in these participants.
- Determine the effect of this drug on breast cancer mortality in these participants.
- Determine the effect of this drug on other cancers, cardiovascular disease, fracture rates, and non-breast cancer deaths in these participants.
- Determine the tolerability and acceptability of side effects of this drug in these participants.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Participants are stratified according to participating center. Participants are randomized to 1 of 2 treatment arms.
- Arm I: Participants receive oral anastrozole daily for 5 years.
- Arm II: Participants receive an oral placebo daily for 5 years. In both arms, treatment continues in the absence of the development of breast cancer (including ductal carcinoma in situ), a drop in the T-score below minus 4, or the occurrence of a new fragility fracture.
Participants are followed for at least a further 5 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
ACCRUAL: A total of 3,864 participants were recruited for this study over 10 years.
- Conditions
- Breast Cancer
- Being tested
- anastrozole, placebo
- Keywords
- breast cancer, chemoprevention
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anastrozoleDrug
Also called Arimidex
aromatase inhibitor
placeboDrug
Arimidex placebo
| Study group | Role | What they receive |
|---|---|---|
| anastrozole | Experimental | anastrozole 1mg Receives: Drug: anastrozole |
| placebo | Placebo comparator | anastrozole 1mg PLACEBO Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years
Measured: Dec 2013
Secondary outcomes (1)
Breast cancer mortality with median follow-up at 10 years
Measured: Dec 2018
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2004 (estimated)
- Study startSep 2003
- Primary completionDec 2013
- Study completion31 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3,864 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jack Cuzick, PhD, Study chair, Queen Mary University of LondonAnthony Howell, Study chair, University of Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00078832
- Sponsor's protocol ID
- ISRCTN31488319
- Other IDs
- EU-20227, EUDRACT-2004-003991-12
- Acronym
- IBIS II
- Status last verified
- Apr 2018
- First submitted
- 8 Mar 2004
- Last updated
- 6 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 25456365Jenkins 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.
PubMed 18768369Sestak 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.
PubMed 29126161Cuzick 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.
PubMed 24333009
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Breast Cancer Intervention Study
- ClinicalTrials.gov ID
- NCT00078832
- Acronym / sponsor ID
- IBIS II / ISRCTN31488319
- Conditions
- Breast Cancer
- Keywords
- breast cancer, chemoprevention
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,864 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Study start
- Sep 2003
- Primary completion
- Dec 2013 (actual)
- Study completion
- 31 May 2021 (actual)
- First posted
- 9 Mar 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- Determine the effectiveness of anastrozole in preventing breast cancer in postmenopausal women at increased risk for the disease.
Secondary
- Determine the role of this drug in preventing estrogen receptor-positive breast cancer in these participants.
- Determine the effect of this drug on breast cancer mortality in these participants.
- Determine the effect of this drug on other cancers, cardiovascular disease, fracture rates, and non-breast cancer deaths in these participants.
- Determine the tolerability and acceptability of side effects of this drug in these participants.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Participants are stratified according to participating center. Participants are randomized to 1 of 2 treatment arms.
- Arm I: Participants receive oral anastrozole daily for 5 years.
- Arm II: Participants receive an oral placebo daily for 5 years. In both arms, treatment continues in the absence of the development of breast cancer (including ductal carcinoma in situ), a drop in the T-score below minus 4, or the occurrence of a new fragility fracture.
Participants are followed for at least a further 5 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
ACCRUAL: A total of 3,864 participants were recruited for this study over 10 years.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| anastrozole | Experimental | Drug: anastrozoleanastrozole 1mg |
| placebo | Placebo comparator | Drug: placeboanastrozole 1mg PLACEBO |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anastrozoleAlso: Arimidexaromatase inhibitor | Drug | anastrozole |
| placeboArimidex placebo | Drug | placebo |
Primary outcome
Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years
Time frame: Dec 2013
1 secondary outcome
Breast cancer mortality with median follow-up at 10 years
Time frame: Dec 2018
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2021.
- Background: PubMed 25456365Sestak 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.
- Background: PubMed 18768369Jenkins 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.
- Background: PubMed 29126161Sestak 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.
- Background: PubMed 24333009Cuzick 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.
- Clinical trial summary from Cancer Research UK WebsiteLink provided by the sponsor.
- IBIS-II websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jack Cuzick, PhD study chair
Queen Mary University of London
Anthony Howell study chair
University of Manchester
74 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing anastrozole in people with Breast Cancer, run by Queen Mary University of London at 74 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 74 sites in United Kingdom, Ireland, Switzerland, Australia, Belgium and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years (time frame: Dec 2013). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00078832, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2021.