Anastrozole versus placebo in post-menopausal women at increased risk of breast cancer
| ISRCTN | ISRCTN31488319 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN31488319 |
| EudraCT/CTIS number | 2004-003991-12 |
| ClinicalTrials.gov number | NCT00078832 |
| Secondary identifying numbers | N/A |
- Submission date
- 07/01/2005
- Registration date
- 26/04/2005
- Last edited
- 24/04/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Contact information
Prof Jack Cuzick
Scientific
Scientific
Centre for Cancer Prevention
Wolfson Institute of Preventive Medicine
Charterhouse Square
London
EC1M 6BQ
United Kingdom
| Phone | +44 (0)20 7882 3504 |
|---|---|
| ibis@qmul.ac.uk |
Miss Joanna Zahedi
Scientific
Scientific
Project Manager/Data Manager
Barts CTU
Centre for Evaluation and Methods
Wolfson Institute of Population Health
Faculty of Medicine and Dentistry
Queen Mary University of London
London
E1 4NS
United Kingdom
| j.zahedi@qmul.ac.uk |
Study information
| Study design | Randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | No longer available |
| Scientific title | An international multi-centre randomised controlled trial of anastrozole versus placebo in post-menopausal women at increased risk of breast cancer |
| Study acronym | IBIS-II Prevention |
| Study hypothesis | Primary hypothesis: To determine if anastrozole is an effective method of preventing breast cancer in postmenopausal women at increased risk of the disease. Secondary hypothesis: 1. To examine the role of anastrozole in preventing oestrogen receptor positive breast cancer 2. To examine the rate of breast cancer occurrence after cessation of anastrozole 3. To examine the effect of anastrozole on breast cancer mortality 4. To examine the effect of anastrozole on other cancers, cardiovascular disease, fracture rates, and non-breast cancer deaths 5. To examine tolerability and acceptability of side effects experienced by women on the study |
| Ethics approval(s) | North West MREC (Multi-centre Research Ethics Committee) and local ethics committees (LREC), 16/09/2002 |
| Condition | Breast cancer |
| Intervention | IBIS-II Prevention is a randomised double blind study investigating the use of anastrozole versus placebo in breast cancer prevention. There are two treatment groups: Group One: anastrozole Group Two: placebo Both the anastrozole and the placebo are tablets that are taken once a day for 5 years. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Anastrozole |
| Primary outcome measure | Breast cancer incidence |
| Secondary outcome measures | Current secondary measures as of 23/02/2012: 1. Breast cancer mortality 2. Cardiovascular events 3. Osteoporosis 4. Other relevant side effects Previous secondary measure: 1. Breast cancer mortality 2. Thromboembolic events 3. Cardiovascular events 4. Osteoporosis 5. Other relevant side effects |
| Overall study start date | 25/05/2003 |
| Overall study end date | 31/05/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 40 Years |
| Upper age limit | 70 Years |
| Sex | Female |
| Target number of participants | Target: 3500. Final: 3864 |
| Total final enrolment | 3864 |
| Participant inclusion criteria | All women must be post-menopausal and between the ages of 40 to 70 years. Postmenopausal status is defined as meeting one or more of the following criteria: 1. Over the age of 60 years 2. Bilateral oophorectomy 3. Aged 60 years or under with a uterus and amenorrhoea for at least 12 months 4. Aged 60 years or under without a uterus and with Follicle-Stimulating Hormone (FSH) more than 30 IU/L The entry criteria will be age-dependent to reflect the increasing baseline risk with age. Aged 45 to 70 years - the entry criteria are based on a relative risk of at least twofold and are similar to IBIS-I. At least one of the following must be satisfied: 1. First degree relative who developed breast cancer at age 50 years or less 2. First degree relative who developed bilateral breast cancer 3. Two or more first or second degree relatives who developed breast or ovarian cancer 4. Nulliparous (or first birth at age 30 years or above) and a first degree relative who developed breast cancer 5. Benign biopsy with proliferative disease and a first degree relative who developed breast cancer 6. Mammographic opacity covering at least 50% of the breast in absence of Hormone Replacement Therapy (HRT) use within the last 3 months Also aged 60 to 70 years - because of their higher baseline risk, women aged 60 to 70 years can enter the study with a smaller relative risk: 7. First degree relative with breast cancer at any age 8. Age at menopause 55 years or older 9. Nulliparous or age at first birth 30 years or above Aged 40 to 44 years - who are postmenopausal (usually because of a bilateral oophorectomy) are eligible if they satisfy one or more of the following criteria (approximately fourfold risk or greater): 10. Two or more first or second degree relatives who developed breast or ovarian cancer at age 50 years or less 11. First degree relative with bilateral breast cancer who developed the first breast cancer at age 50 years or less 12. Nulliparous (or first birth at age 30 years or above) and a first degree relative who developed breast cancer at age 40 years or less 13. Benign biopsy with proliferative disease and a first degree relative who developed breast cancer at age 40 years or less All age groups (40 to 70 years) - women who have had certain breast conditions will also be eligible. These are: 14. Lobular Carcinoma In Situ (LCIS) 15. Atypical ductal or lobular hyperplasia in a benign lesion 16. Ductal Carcinoma In Situ (DCIS), diagnosed within the last six months, and treated by mastectomy. Oestrogen Receptor (ER) or Progesterone Receptor (PgR) status of DCIS must be known, and must be greater than 5% positive cells. 17. Women with a ten year risk greater than 5%, who do not fit into the above categories (risk equivalent). All risk equivalent women must be approved by the Steering Committee Co-Chairman (London IBIS central office). These women must have clearly apparent family history and/or other risk factors indicating appropriate increased risk of breast cancer for their age. Particularly careful assessment of the risk-benefit for these women should be undertaken before a woman from this group is entered. All women must have: 1. Had a mammogram taken within the last year and showing no evidence of breast cancer 2. Had a baseline bone mineral density scan within the last 2 years (dual-energy X-ray absorptiometry [DXA] either of hip, lumbar spine, forearm) and spinal X-ray 3. Signed a consent form after receiving full information about the study |
| Participant exclusion criteria | Current exclusion criteria as of 23/02/2012 1. Still having periods 2. Have breast cancer, or have had breast cancer in the past (unless you have had DCIS - see criteria for specific age groups) 3. Have had any other cancer in the last five years (except non-melanoma skin cancer or carcinoma in situ of the cervix or Hodgkin's disease if before the age of 30 and treated with mantle therapy. 4. Have had tamoxifen, raloxifene or other Selective Estrogen Receptor Modulators (SERMs) for more than six months in the past 5 years. (women in IBIS-1 are eligible if they have been off the therapy for more than five years. 5. Want to carry on taking HRT that contains oestrogen 6. Have had (or are planning to have) your breast(s) removed (a mastectomy) to try and prevent breast cancer 7. Have any other serious medical conditions 8. have had treatment with non-approved experimental drugs during the 6 months before randomisation. 9. History of Lactose or gluten intolerance. 10. Life expectancy of less than 10 years or other medical condition which would significantly interfere with the ability to accept the trial treatment. Previous exclusion criteria 1. Still having periods 2. Have breast cancer, or have had breast cancer in the past (unless you have had DCIS - see criteria for specific age groups) 3. Have had any other cancer in the last five years (except non-melanoma skin cancer or carcinoma in situ of the cervix) 4. Have had tamoxifen, raloxifene or other Selective Estrogen Receptor Modulators (SERMs) for more than three months in the past 5. Have taken part in the IBIS 1 trial 6. Want to carry on taking HRT that contains oestrogen 7. Have had (or are planning to have) your breast(s) removed (a mastectomy) to try and prevent breast cancer 8. Have any other serious medical conditions 9. Have taken any other drug as part of a clinical trial within the last three months |
| Recruitment start date | 25/05/2003 |
| Recruitment end date | 31/01/2012 |
Locations
Countries of recruitment
- Australia
- Belgium
- Chile
- Denmark
- Egypt
- England
- Finland
- Germany
- Hungary
- Ireland
- Italy
- Malta
- New Zealand
- Pakistan
- Peru
- Portugal
- Russian Federation
- Switzerland
- Türkiye
- United Kingdom
Study participating centre
Centre for Cancer Prevention
London
EC1M 6BQ
United Kingdom
EC1M 6BQ
United Kingdom
Sponsor information
Queen Mary University of London (UK)
University/education
University/education
Dr Mays Jawad
Research & Development Governance Operations Manager
Joint Research Management Office
5 Walden Street
London
E1 2EF
England
United Kingdom
| Phone | +44 (0)20 7882 7275 |
|---|---|
| sponsorsrep@bartshealth.nhs.uk | |
| Website | http://www.jrmo.org.uk/ |
"ROR" |
https://ror.org/026zzn846 |
Funders
Funder type
Charity
Cancer Research UK (CRUK) (UK)
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | The first major analysis was completed in 2013 (https://pubmed.ncbi.nlm.nih.gov/24333009/), a major follow up analysis was published in 2019 (https://pubmed.ncbi.nlm.nih.gov/31839281/). The final analysis for purposes of CSR is to be completed in 2021. Follow up is now conducted via a new long-term follow-up study on a separate protocol (REC 19/LO/0984, IRAS 258590) (study registration pending). The next major follow-up is not due until 2024. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | No | Yes | |||
| Protocol article | protocol | 01/12/2003 | Yes | No | |
| Results article | cognition substudy results | 01/10/2008 | Yes | No | |
| Results article | results | 22/03/2014 | Yes | No | |
| Results article | substudy results | 01/12/2014 | Yes | No | |
| Results article | adherence results | 01/02/2018 | Yes | No | |
| Results article | results | 03/03/2021 | 04/03/2021 | Yes | No |
| Results article | long-term results | 12/12/2019 | 06/10/2021 | Yes | No |
| Other publications | Results of case control study of IBIS-II participants measuring serum hormone levels | 05/12/2023 | 11/12/2023 | Yes | No |
Editorial Notes
24/04/2025: Contact details updated.
11/12/2023: Publication reference added.
06/10/2021: The following changes were made to the trial record:
1. The overall trial end date was changed from 31/01/2022 to 31/05/2021.
2. Publication and dissemination plan, IPD sharing statement and publication reference added.
3. Total final enrolment number added.
04/03/2021: Publication reference added.
10/01/2019: The Cancer Research UK plain English summary link has been updated.
09/01/2019: The following changes have been made:
1. The final enrolment number was added.
2. The participant information sheet link (http://www.ibis-trials.org/docs/leaflets/IBIS-II_leaflet.pdf ) has been removed, since it is no longer available.
3. Belgium, Chile, Denmark, Finland, Hungary, Ireland, Malta and Portugal were added to the countries of recruitment. Trial centres in Egypt, Pakistan, Peru, Russia and Turkey were opened but were closed prematurely.
4. The sponsor contact details have been updated.
5. Publication references added.
19/10/2018: Cancer Research UK lay results summary link added to Results (plain English)
23/02/2012: The following changes were made to the study record:
1. The overall study end date was changed from 31/12/2011 to 31/01/2022.
2. The target number of participants was changed from 6000 to 3500.
3. France and Austria were removed from the countries of recruitment.
08/02/2011: The overall trial end date was changed from 31/12/2010 to 31/12/2011.
