Breast CancerPhase 3IBIS-II DCISNCT00072462
Adjuvant Tamoxifen Compared With Anastrozole in Treating Postmenopausal Women With Ductal Carcinoma In Situ
A Phase 3 study testing tamoxifen citrate and Anastrozole in people with Breast Cancer, run by Queen Mary University of London at 97 sites in 14 countries.
Trial summary
RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using either tamoxifen or anastrozole may fight breast cancer by blocking the use of estrogen. Read more about this study
- Who is it for?
- Ages 40 to 70 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- tamoxifen citrate and Anastrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,980 participants
- Where
- 97 sitesin 14 countries
- Study dates
- Sep 2003to 31 May 2021
- Phase
- Phase 3
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
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of ductal carcinoma in situ within the past 6 months
- Locally excised with tumor-free margins at least 1 mm
- Hormone receptor status:
- Estrogen or progesterone receptor positive
- Equal to or greater than 5% positive cells
PATIENT CHARACTERISTICS:
Age
- 40 to 70
Sex
- Female
Menopausal status
- Postmenopausal, defined as meeting at least 1 of the following criteria:
- Over age 60
- Prior bilateral oophorectomy
- Age 60 or under with a uterus AND amenorrhea for at least the past 12 months
- Age 60 or under without a uterus AND follicle-stimulating hormone greater than 20 IU/L
Performance status
- Not specified
Life expectancy
- At least 10 years
Hematopoietic
- Not specified
Hepatic
- Not specified
Renal
- Not specified
Cardiovascular
- No prior deep vein thrombosis
- No prior transient ischemic attack
- No prior cerebrovascular accident
Pulmonary
- No prior pulmonary embolism
Other
- No unexplained postmenopausal bleeding
- No other cancer within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
- No other concurrent medical condition that would preclude study therapy, place the patient at unusual risk, or confound study results
- No evidence of osteoporosis
- Fragility fractures within the spine allowed if T-score level is greater than -4 and consist of no more than 2 fractures
- Psychologically and physically suitable for 5 years of study therapy
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Not specified
Endocrine therapy
- No prior or concurrent tamoxifen use lasting more than 6 months unless treatment was completed more than 5 years ago. Women in IBIS-I can join if off trial therapy for at least 5 years.
- No prior or concurrent raloxifene use lasting more than 6 months unless treatment was completed more than 5 years ago.
- No other prior or concurrent selective estrogen-receptor modulator use lasting more than 6 months unless treatment was completed more than 5 years ago
- No concurrent systemic estrogen-based hormone replacement therapy, including vaginal estrogen preparations
Radiotherapy
- Not specified
Surgery
- See Disease Characteristics
- No prior mastectomy
- No planned prophylactic mastectomy
Other
- At least 3 months since prior unapproved or experimental agents
- No concurrent anticoagulants
Trial locations and contacts
97 sites in 14 countries.
97 sites in 14 countries
United Kingdom50 sites
Aberdeen Royal Infirmary
Aberdeen, AB25 2ZA
Tameside General Hospital
Ashton-under-Lyne, OL6 9RW
Centre for Cancer Research and Cell Biology at Queen's University Belfast
Belfast, Northern Ireland, BT9 7AB
Royal Bolton Hospital
Bolton, BL4 0JR
Royal Bournemouth Hospital
Bournemouth, BH7 7DW
St Lukes Hospital
Bradford, BD5 0NA
Royal Sussex County Hospital
Brighton, BN2 5BE
Frenchay Hospital
Bristol, England, BS16 1LE
Bristol Infirmary
Bristol, BS2 8ED
Queens Hospital Burton
Burton, DE13 0RB
University Hospital of Wales
Cardiff, Wales, CF14 4XN
Cheltenham General Hospital
Cheltenham, GL53 7AN
Countess of Chester Hospital
Chester, CH2 1UL
Colchester General Hospital
Colchester, England, CO4 5JL
Derbyshire Royal Infirmary
Derby, DE1 2QY
Ninewells Hospital
Dundee, Scotland, DD1 9SY
Royal Infirmary of Edinburgh at Little France
Edinburgh, Scotland, EH3 9YW
St Margaret's Hospital
Epping, CM16 6TN
Royal Devon and Exeter Hospital
Exeter, EX2 5DW
Frimley Park Hospital NHS Trust
Frimley, GU16 7UJ
Grantham & District Hospital
Grantham, NG31 8NG
Conquest Hospital, The Ridge
Hastings, TN37 7RD
Huddersfield Royal Infirmary
Huddersfield, HD3 3EA
Castle Hill Hospital
Hull, HU16 5JQ
Airedale General Hospital
Keighley, BD20 6TD
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, LS9 7TF
Leeds St James.
Leeds, LS9 7TF
Lincoln County Hospital
Lincoln, LN2 5QY
Royal Liverpool University Hospital
Liverpool, England, L7 8XP
Whittington Hospital
London, England, N19 5NF
St. Thomas' Hospital
London, England, SE1 9RT
St. Bartholomew's Hospital
London, Please Select, EC1A 7BE
Royal Marsden Hospital
London, Please Select, SW3 6JJ
Christie Hospital
Manchester, England, M20 4BX
Newcastle Upon Tyne Hospitals NHS Trust
Newcastle upon Tyne, England, NE1 4LP
Nottingham City Hospital
Nottingham, England, NG5 1PB
Derriford Hospital
Plymouth, PL6 8BX
Royal Hospital Haslar
Portsmouth, PO12 2AA
Scarborough NHS Trust
Scarborough, YO12 6QL
Weston Park Hospital
Sheffield, S10 2SJ
Royal South Hants Hospital
Southampton, England, SO14 0YG
Staffordshire General Hospital
Stafford, ST16 3SA
Singleton Hospital
Swansea, SA2 8QA
Treliske Royal Cornwall Hospital
Truro, TR1 3LJ
Clayton Hospital, Northgate
Wakefield, WF1 3JS
Welwyn Garden City Hospital
Welwyn, AL7 4HQ
Wishaw General Hospital
Wishaw, ML2 0DP
Worthing Hospital
Worthing, BN11 2DH
Yeovil District Hospital
Yeovil, BA21 4AT
York Hospital
York, YO31 8HE
France20 sites
Institut Sainte Catherine
Avignon, 84082
Institut Bergonie
Bordeaux, 33076
Polyclinique Bordeaux Nord Aquitaine
Bordeaux, 33300
Clinique Tivoli
Bordeaux, F-33000
CHU Hopital A. Morvan
Brest, 29609
Centre Regional Francois Baclesse
Caen, 14076
Centre Jean Perrin
Clermont-Ferrand, 63011
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Dijon, 21079
Centre Hospitalier de Lagny
Lagny-sur-Marne, 77405
CMC Les Ormeaux
Le Havre, 76600
Centre Oscar Lambret
Lille, 59020
Centre Hospital Regional Universitaire de Limoges
Limoges, 87042
Centre Hospitalier de Mulhouse
Mulhouse, 68051
Centre Regional Rene Gauducheau
Nantes, 44805
Clinique Saint - Pierre
Perpignan
Institut Jean Godinot
Reims, 51056
Centre Eugene Marquis
Rennes, 35042
Centre Henri Becquerel
Rouen, 76038
Institut Claudius Regaud
Toulouse, 31052
Institut Gustave Roussy
Villejuif, F-94805
Switzerland9 sites
Inselspital Bern
Bern, CH-3010
Oncocare Sonnenhof-Klinik Engeriedspital
Bern, CH-3012
Hopital Cantonal Universitaire de Geneve
Geneva, CH-1211
Centre Hospitalier Universitaire Vaudois
Lausanne, CH-1011
Kantonspital
Lucerne, CH-6000
Ospedale Beata Vergine
Mendrisio, CH-6850
Tumor Zentrum ZeTup St. Gallen und Chur
Sankt Gallen, CH-9006
Switzerland(St. Gallen)
Sankt Gallen
Regionalspital
Thun, 3600
Ireland8 sites
Cork Infirmary
Cork
Cork University Hospital
Cork
Beaumont Hospital
Dublin
St. Vincent's University Hospital
Dublin
University College Hospital
Galway
Mid-Western Regional Hospital
Limerick
Sligo General Hospital
Sligo
The Adelaide and Meath Hospital
Tallaght
About this study
Official title: International Breast Cancer Intervention Study II (IBIS-II) (DCIS)
RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using either tamoxifen or anastrozole may fight breast cancer by blocking the use of estrogen. It is not yet known whether tamoxifen is more effective than anastrozole in preventing breast cancer after surgery for ductal carcinoma in situ.
PURPOSE: This randomized phase III trial is studying how well adjuvant tamoxifen works compared to anastrozole in treating postmenopausal women who have undergone surgery to remove ductal carcinoma in situ.
Read the detailed description
OBJECTIVES:
Primary
- Compare the efficacy of adjuvant tamoxifen vs anastrozole, in terms of local control and prevention of contralateral disease, in postmenopausal women with locally excised ductal carcinoma in situ.
- Compare side effect profiles of these drugs in these patients.
Secondary
- Compare the efficacy of these drugs, according to the receptor status of the primary or recurrent cancer in these patients.
- Compare the rate of breast cancer recurrence and growth of new contralateral tumors after cessation of treatment with these drugs in these patients.
- Compare breast cancer mortality in patients treated with these drugs.
- Compare the effect of these drugs on other cancers, cardiovascular disease, fracture rates, and non-breast cancer deaths in these patients.
- Compare the tolerability and acceptability of side effects experienced by patients treated with these drugs.
OUTLINE: This is a randomized, double-blind, multicentre study. Patients are stratified according to participating centre. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral tamoxifen and oral placebo once daily.
- Arm II: Patients receive oral anastrozole and oral placebo once daily. In both arms, treatment continues for 5 years in the absence of disease recurrence or unacceptable toxicity.
Patients are followed annually for 5 years and a further 5 years (minimum) off treatment.
Peer Reviewed and Funded by Cancer Research UK. Sponsored by Queen Mary University of London
ACTUAL ACCRUAL: A total of 2,980 patients were accrued for this study over 9 years.
- Conditions
- Breast Cancer
- Being tested
- tamoxifen citrate, Anastrozole
- Keywords
- ductal breast carcinoma in situ, breast cancer in situ
- Medical subject headings
- Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating, Breast Carcinoma In Situ
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tamoxifen citrateDrug
Also called Nolvadex
Tamoxifen 20mg + Anastrozole placebo
AnastrozoleDrug
Also called Arimidex
Anastrozole 1mg + Tamoxifen placebo
| Study group | Role | What they receive |
|---|---|---|
| Anastrozole | Active comparator | Not described Receives: Drug: Anastrozole |
| Tamoxifen | Active comparator | Not described Receives: Drug: tamoxifen citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours
Measured: Date of the breast cancer occurrence is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5).
Secondary outcomes (4)
Number of Participants With ER+ Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours
Measured: Date of the breast cancer occurrence is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5).
Number of Participants With ER- Breast Cancer Recurrence
Measured: Date of the breast cancer occurrence is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5).
Number of Breast Cancer Deaths
Measured: Date of the death is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5).
Number of Non-breast Cancer Deaths
Measured: Date of the death is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2003 (estimated)
- Study startSep 2003
- Primary completionDec 2015
- Study completion31 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,980 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK
- 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
- NCT00072462
- Sponsor's protocol ID
- ISRCTN37546358
- Other IDs
- EU-20226, BIG-5-02, IBCSG-31-03-DCIS, ISRCTN31488319
- Acronym
- IBIS-II DCIS
- Status last verified
- Apr 2024
- First submitted
- 4 Nov 2003
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Juraskova 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 Expect. 2008 Sep;11(3):252-62. doi: 10.1111/j.1369-7625.2008.00498.x.
PubMed 18816321Forbes JF, Sestak I, Howell A, Bonanni B, Bundred N, Levy C, von Minckwitz G, Eiermann W, Neven P, Stierer M, Holcombe C, Coleman RE, Jones L, Ellis I, Cuzick J; IBIS-II investigators. Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial. Lancet. 2016 Feb 27;387(10021):866-73. doi: 10.1016/S0140-6736(15)01129-0. Epub 2015 Dec 11.
PubMed 26686313Sestak 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 29126161