Adjuvant Tamoxifen Compared With Anastrozole in Treating Postmenopausal Women With Ductal Carcinoma In Situ

NCT00072462 | Completed Phase 3 Results DMC

• 5 other identifiers: ISRCTN37546358EU-20226BIG-5-02IBCSG-31-03-DCISISRCTN31488319
• Study Type: interventional
• Target: 2,980
• Locations: 13 countries
• Sites: 96

Brief 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. 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.

Conditions

Breast Cancer

Keywords

ductal breast carcinoma in situ; breast cancer in situ

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours

  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

  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

  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

  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

  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).

Study Arms (2)

Anastrozole

ACTIVE COMPARATOR

Drug: Anastrozole

Tamoxifen

ACTIVE COMPARATOR

Drug: tamoxifen citrate

Interventions

tamoxifen citrate DRUG

Tamoxifen 20mg + Anastrozole placebo

Also known as: Nolvadex

Tamoxifen

Anastrozole DRUG

Anastrozole 1mg + Tamoxifen placebo

Also known as: Arimidex

Anastrozole

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Queen Mary University of London: lead
• Cancer Research UK: collaborator

Study Sites (97)

Australia

Newcastle, Australia

Location

Austrian Breast & Colorectal Cancer Study Group

Vienna, Austria

Location

Belgium

Leuven, Belgium

Location

Chile

Santiago, Chile

Location

Institut Sainte Catherine

Avignon, 84082, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, 33300, France

Location

Clinique Tivoli

Bordeaux, F-33000, France

Location

CHU Hopital A. Morvan

Brest, 29609, France

Location

Centre Regional Francois Baclesse

Caen, 14076, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, 21079, France

Location

Centre Hospitalier de Lagny

Lagny-sur-Marne, 77405, France

Location

CMC Les Ormeaux

Le Havre, 76600, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Hospital Regional Universitaire de Limoges

Limoges, 87042, France

Location

Centre Hospitalier de Mulhouse

Mulhouse, 68051, France

Location

Centre Regional Rene Gauducheau

Nantes, 44805, France

Location

Clinique Saint - Pierre

Perpignan, France

Location

Institut Jean Godinot

Reims, 51056, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

Institut Gustave Roussy

Villejuif, F-94805, France

Location

Germany

Neu-Isenburg, Germany

Location

Hungary

Szeged, Hungary

Location

Cork Infirmary

Cork, Ireland

Location

Cork University Hospital

Cork, Ireland

Location

Beaumont Hospital

Dublin, Ireland

Location

St. Vincent's University Hospital

Dublin, Ireland

Location

University College Hospital

Galway, Ireland

Location

Mid-Western Regional Hospital

Limerick, Ireland

Location

Sligo General Hospital

Sligo, Ireland

Location

The Adelaide and Meath Hospital

Tallaght, Ireland

Location

European Institute of Oncology

Milan, Italy

Location

Sir Paul Boffa Hospital,

Floriana, Malta

Location

Sweden

Lund, Sweden

Location

Inselspital Bern

Bern, CH-3010, Switzerland

Location

Oncocare Sonnenhof-Klinik Engeriedspital

Bern, CH-3012, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonspital

Lucerne, CH-6000, Switzerland

Location

Ospedale Beata Vergine

Mendrisio, CH-6850, Switzerland

Location

Tumor Zentrum ZeTup St. Gallen und Chur

Sankt Gallen, CH-9006, Switzerland

Location

Switzerland(St. Gallen)

Sankt Gallen, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

Turkey(Istanbul University)

Istanbul, Turkey (Türkiye)

Location

Frenchay Hospital

Bristol, England, BS16 1LE, United Kingdom

Location

Colchester General Hospital

Colchester, England, CO4 5JL, United Kingdom

Location

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, England, L7 8XP, United Kingdom

Location

Whittington Hospital

London, England, N19 5NF, United Kingdom

Location

St. Thomas' Hospital

London, England, SE1 9RT, United Kingdom

Location

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

Newcastle Upon Tyne Hospitals NHS Trust

Newcastle upon Tyne, England, NE1 4LP, United Kingdom

Location

Nottingham City Hospital

Nottingham, England, NG5 1PB, United Kingdom

Location

Royal South Hants Hospital

Southampton, England, SO14 0YG, United Kingdom

Location

Centre for Cancer Research and Cell Biology at Queen's University Belfast

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

St. Bartholomew's Hospital

London, Please Select, EC1A 7BE, United Kingdom

Location

Royal Marsden Hospital

London, Please Select, SW3 6JJ, United Kingdom

Location

Ninewells Hospital

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Royal Infirmary of Edinburgh at Little France

Edinburgh, Scotland, EH3 9YW, United Kingdom

Location

University Hospital of Wales

Cardiff, Wales, CF14 4XN, United Kingdom

Location

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZA, United Kingdom

Location

Tameside General Hospital

Ashton-under-Lyne, OL6 9RW, United Kingdom

Location

Royal Bolton Hospital

Bolton, BL4 0JR, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

St Lukes Hospital

Bradford, BD5 0NA, United Kingdom

Location

Royal Sussex County Hospital

Brighton, BN2 5BE, United Kingdom

Location

Bristol Infirmary

Bristol, BS2 8ED, United Kingdom

Location

Queens Hospital Burton

Burton, DE13 0RB, United Kingdom

Location

Cheltenham General Hospital

Cheltenham, GL53 7AN, United Kingdom

Location

Countess of Chester Hospital

Chester, CH2 1UL, United Kingdom

Location

Derbyshire Royal Infirmary

Derby, DE1 2QY, United Kingdom

Location

St Margaret's Hospital

Epping, CM16 6TN, United Kingdom

Location

Royal Devon and Exeter Hospital

Exeter, EX2 5DW, United Kingdom

Location

Frimley Park Hospital NHS Trust

Frimley, GU16 7UJ, United Kingdom

Location

Grantham & District Hospital

Grantham, NG31 8NG, United Kingdom

Location

Conquest Hospital, The Ridge

Hastings, TN37 7RD, United Kingdom

Location

Huddersfield Royal Infirmary

Huddersfield, HD3 3EA, United Kingdom

Location

Castle Hill Hospital

Hull, HU16 5JQ, United Kingdom

Location

Airedale General Hospital

Keighley, BD20 6TD, United Kingdom

Location

Leeds St James.

Leeds, LS9 7TF, United Kingdom

Location

Lincoln County Hospital

Lincoln, LN2 5QY, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8BX, United Kingdom

Location

Royal Hospital Haslar

Portsmouth, PO12 2AA, United Kingdom

Location

Scarborough NHS Trust

Scarborough, YO12 6QL, United Kingdom

Location

Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

Location

Staffordshire General Hospital

Stafford, ST16 3SA, United Kingdom

Location

Singleton Hospital

Swansea, SA2 8QA, United Kingdom

Location

Treliske Royal Cornwall Hospital

Truro, TR1 3LJ, United Kingdom

Location

Clayton Hospital, Northgate

Wakefield, WF1 3JS, United Kingdom

Location

Welwyn Garden City Hospital

Welwyn, AL7 4HQ, United Kingdom

Location

Wishaw General Hospital

Wishaw, ML2 0DP, United Kingdom

Location

Worthing Hospital

Worthing, BN11 2DH, United Kingdom

Location

Yeovil District Hospital

Yeovil, BA21 4AT, United Kingdom

Location

York Hospital

York, YO31 8HE, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 18816321 BACKGROUND

• Forbes 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.

  PMID: 26686313 BACKGROUND

• 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.

  PMID: 29126161 BACKGROUND

Related Links

• Clinical trial summary from Cancer Research UK Website
• IBIS-II website

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Breast Carcinoma In Situ

Interventions

Tamoxifen; Anastrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

This CTIMP trial, which recruited between 03 Mar 2003 and 08 Feb 2012, formally ended on 31 May 2021.

Results Point of Contact

• Title: Professor Jack Cuzick
• Organization: Queen Mary University of London

j.cuzick@qmul.ac.uk

+442078823504

Study Officials

• Jack Cuzick, PhD

  Queen Mary University of London

  STUDY CHAIR

• Anthony Howell

  University of Manchester

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2003
• First Posted: November 6, 2003
• Study Start: September 1, 2003
• Primary Completion: December 1, 2015
• Study Completion: May 31, 2021
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-04

Locations

FR (20); BE (1); IE (8); MA (1); SE (1); CH (9); GB (50); HU (1); DE (1); IT (1); TU (1); AU (1); CL (1)