Adjuvant Tamoxifen Compared With Anastrozole in Treating Postmenopausal Women With Ductal Carcinoma In Situ (IBIS-II DCIS)

October 5, 2021 updated by: Queen Mary University of London

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

2980

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Newcastle, Australia
        • Australia
  • Austria
      • Vienna, Austria
        • Austrian Breast & Colorectal Cancer Study Group
  • Belgium
      • Leuven, Belgium
        • Belgium
  • Chile
      • Santiago, Chile
        • Chile
  • France
      • Avignon, France, 84082
        • Institut Sainte Catherine
      • Bordeaux, France, 33076
        • Institut Bergonié
      • Bordeaux, France, 33300
        • Polyclinique Bordeaux Nord Aquitaine
      • Bordeaux, France, F-33000
        • Clinique Tivoli
      • Brest, France, 29609
        • CHU Hopital A. Morvan
      • Caen, France, 14076
        • Centre Regional Francois Baclesse
      • Clermont-Ferrand, France, 63011
        • Centre Jean Perrin
      • Dijon, France, 21079
        • Centre de Lutte Contre le Cancer Georges-Francois Leclerc
      • Lagny Sur Marne, France, 77405
        • Centre Hospitalier de Lagny
      • Le Havre, France, 76600
        • CMC Les Ormeaux
      • Lille, France, 59020
        • Centre Oscar Lambret
      • Limoges, France, 87042
        • Centre Hospital Regional Universitaire de Limoges
      • Mulhouse, France, 68051
        • Centre Hospitalier de Mulhouse
      • Nantes, France, 44805
        • Centre Regional Rene Gauducheau
      • Perpignan, France
        • Clinique Saint - Pierre
      • Reims, France, 51056
        • Institut Jean Godinot
      • Rennes, France, 35042
        • Centre Eugène Marquis
      • Rouen, France, 76038
        • Centre Henri Becquerel
      • Toulouse, France, 31052
        • Institut Claudius Regaud
      • Villejuif, France, F-94805
        • Institut Gustave Roussy
  • Germany
      • Neu-Isenburg, Germany
        • Germany
  • Hungary
      • Szeged, Hungary
        • Hungary
  • Ireland
      • Cork, Ireland
        • Cork University Hospital
      • Cork, Ireland
        • Cork Infirmary
      • Dublin, Ireland
        • Beaumont Hospital
      • Dublin, Ireland
        • St. Vincent's University Hospital
      • Galway, Ireland
        • University College Hospital
      • Limerick, Ireland
        • Mid-Western Regional Hospital
      • Sligo, Ireland
        • Sligo General Hospital
      • Tallaght, Ireland
        • The Adelaide and Meath Hospital
  • Italy
      • Milan, Italy
        • European Institute of Oncology
  • Malta
      • Floriana, Malta
        • Sir Paul Boffa Hospital,
  • Sweden
      • Lund, Sweden
        • Sweden
  • Switzerland
      • (St. Gallen), Switzerland
        • Switzerland(St. Gallen)
      • Bern, Switzerland, CH-3010
        • Inselspital Bern
      • Bern, Switzerland, CH-3012
        • Oncocare Sonnenhof-Klinik Engeriedspital
      • Geneva, Switzerland, CH-1211
        • Hopital Cantonal Universitaire de Geneve
      • Lausanne, Switzerland, CH-1011
        • Centre Hospitalier Universitaire Vaudois
      • Luzern, Switzerland, CH-6000
        • Kantonspital
      • Mendrisio, Switzerland, CH-6850
        • Ospedale Beata Vergine
      • St. Gallen, Switzerland, CH-9006
        • Tumor Zentrum ZeTup St. Gallen und Chur
      • Thun, Switzerland, 3600
        • Regionalspital
  • Turkey
      • Istanbul, Turkey
        • Turkey(Istanbul University)
  • United Kingdom
      • Aberdeen, United Kingdom, AB25 2ZA
        • Aberdeen Royal Infirmary
      • Ashton under Lyne, United Kingdom, OL6 9RW
        • Tameside General Hospital
      • Bolton, United Kingdom, BL4 0JR
        • Royal Bolton Hospital
      • Bournemouth, United Kingdom, BH7 7DW
        • Royal Bournemouth Hospital
      • Bradford, United Kingdom, BD5 0NA
        • St Lukes Hospital
      • Brighton, United Kingdom, BN2 5BE
        • Royal Sussex County Hospital
      • Bristol, United Kingdom, BS2 8ED
        • Bristol Infirmary
      • Burton, United Kingdom, DE13 0RB
        • Queens Hospital Burton
      • Cheltenham, United Kingdom, GL53 7AN
        • Cheltenham General Hospital
      • Chester, United Kingdom, CH2 1UL
        • Countess of Chester Hospital
      • Derby, United Kingdom, DE1 2QY
        • Derbyshire Royal Infirmary
      • Epping, United Kingdom, CM16 6TN
        • St Margaret's Hospital
      • Exeter, United Kingdom, EX2 5DW
        • Royal Devon and Exeter Hospital
      • Frimley, United Kingdom, GU16 7UJ
        • Frimley Park Hospital NHS Trust
      • Grantham, United Kingdom, NG31 8NG
        • Grantham & District Hospital
      • Hastings, United Kingdom, TN37 7RD
        • Conquest Hospital, The Ridge
      • Huddersfield, United Kingdom, HD3 3EA
        • Huddersfield Royal Infirmary
      • Hull, United Kingdom, HU16 5JQ
        • Castle Hill Hospital
      • Keighley, United Kingdom, BD20 6TD
        • Airedale General Hospital
      • Leeds, United Kingdom, LS9 7TF
        • Leeds St James.
      • Lincoln, United Kingdom, LN2 5QY
        • Lincoln County Hospital
      • Plymouth, United Kingdom, PL6 8BX
        • Derriford Hospital
      • Portsmouth, United Kingdom, PO12 2AA
        • Royal Hospital Haslar
      • Scarborough, United Kingdom, YO12 6QL
        • Scarborough NHS Trust
      • Sheffield, United Kingdom, S10 2SJ
        • Weston Park Hospital
      • Stafford, United Kingdom, ST16 3SA
        • Staffordshire General Hospital
      • Swansea, United Kingdom, SA2 8QA
        • Singleton Hospital
      • Truro, United Kingdom, TR1 3LJ
        • Treliske Royal Cornwall Hospital
      • Wakefield, United Kingdom, WF1 3JS
        • Clayton Hospital, Northgate
      • Welwyn, United Kingdom, AL7 4HQ
        • Welwyn Garden City Hospital
      • Wishaw, United Kingdom, ML2 0DP
        • Wishaw General Hospital
      • Worthing, United Kingdom, BN11 2DH
        • Worthing Hospital
      • Yeovil, United Kingdom, BA21 4AT
        • Yeovil District Hospital
      • York, United Kingdom, YO31 8HE
        • York Hospital
    • England
      • Bristol, England, United Kingdom, BS16 1LE
        • Frenchay Hospital
      • Colchester, England, United Kingdom, CO4 5JL
        • Colchester General Hospital
      • Leeds, England, United Kingdom, LS9 7TF
        • Leeds Cancer Centre at St. James's University Hospital
      • Liverpool, England, United Kingdom, L7 8XP
        • Royal Liverpool University Hospital
      • London, England, United Kingdom, SE1 9RT
        • St. Thomas' Hospital
      • London, England, United Kingdom, N19 5NF
        • Whittington Hospital
      • Manchester, England, United Kingdom, M20 4BX
        • Christie Hospital
      • Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
        • Newcastle Upon Tyne Hospitals NHS Trust
      • Nottingham, England, United Kingdom, NG5 1PB
        • Nottingham City Hospital
      • Southampton, England, United Kingdom, SO14 0YG
        • Royal South Hants Hospital
    • Northern Ireland
      • Belfast, Northern Ireland, United Kingdom, BT9 7AB
        • Centre for Cancer Research and Cell Biology at Queen's University Belfast
    • Please Select
      • London, Please Select, United Kingdom, EC1A 7BE
        • St. Bartholomew's Hospital
      • London, Please Select, United Kingdom, SW3 6JJ
        • Royal Marsden Hospital
    • Scotland
      • Dundee, Scotland, United Kingdom, DD1 9SY
        • Ninewells Hospital
      • Edinburgh, Scotland, United Kingdom, EH3 9YW
        • Royal Infirmary of Edinburgh at Little France
    • Wales
      • Cardiff, Wales, United Kingdom, CF14 4XN
        • University Hospital of Wales

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Tamoxifen
Drug: tamoxifen citrate
Tamoxifen 20mg + Anastrozole placebo
Other Names:
  • Nolvadex
Active Comparator: Anastrozole
Drug: Anastrozole
Anastrozole 1mg + Tamoxifen placebo
Other Names:
  • Arimidex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
To examine the effect of tamoxifen vs anastrozole on breast cancer mortality
Time Frame: 7 years
7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Queen Mary University of London

Collaborators

Cancer Research UK

Investigators

  • Study Chair: Jack Cuzick, PhD, Queen Mary University of London
  • Study Chair: Anthony Howell, University of Manchester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2003

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

May 31, 2021

Study Registration Dates

First Submitted

November 4, 2003

First Submitted That Met QC Criteria

November 5, 2003

First Posted (Estimate)

November 6, 2003

Study Record Updates

Last Update Posted (Actual)

October 6, 2021

Last Update Submitted That Met QC Criteria

October 5, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISRCTN37546358
  • EU-20226
  • BIG-5-02
  • IBCSG-31-03-DCIS
  • ISRCTN31488319

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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