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

Breast Cancer Clinical Trial

— IBIS-II DCIS  

Official title:

International Breast Cancer Intervention Study II (IBIS-II) (DCIS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00072462
• Other study ID #: ISRCTN37546358
• Secondary ID: EU-20226BIG-5-02
• Status: Completed
• Phase: Phase 3
• Start date: September 2003
• Est. completion date: May 31, 2021

Study information

• Verified date: September 2021
• Source: Queen Mary University of London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2980
• Est. completion date: May 31, 2021
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Carcinoma in Situ

Intervention

Drug:
• tamoxifen citrate
Tamoxifen 20mg + Anastrozole placebo
• Anastrozole
Anastrozole 1mg + Tamoxifen placebo

Locations

Country	Name	City	State
Australia	Australia	Newcastle
Austria	Austrian Breast & Colorectal Cancer Study Group	Vienna
Belgium	Belgium	Leuven
Chile	Chile	Santiago
France	Institut Sainte Catherine	Avignon
France	Clinique Tivoli	Bordeaux
France	Institut Bergonie	Bordeaux
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	CHU Hopital A. Morvan	Brest
France	Centre Regional Francois Baclesse	Caen
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon
France	Centre Hospitalier de Lagny	Lagny Sur Marne
France	CMC Les Ormeaux	Le Havre
France	Centre Oscar Lambret	Lille
France	Centre Hospital Regional Universitaire de Limoges	Limoges
France	Centre Hospitalier de Mulhouse	Mulhouse
France	Centre Regional Rene Gauducheau	Nantes
France	Clinique Saint - Pierre	Perpignan
France	Institut Jean Godinot	Reims
France	Centre Eugene Marquis	Rennes
France	Centre Henri Becquerel	Rouen
France	Institut Claudius Regaud	Toulouse
France	Institut Gustave Roussy	Villejuif
Germany	Germany	Neu-Isenburg
Hungary	Hungary	Szeged
Ireland	Cork Infirmary	Cork
Ireland	Cork University Hospital	Cork
Ireland	Beaumont Hospital	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Ireland	University College Hospital	Galway
Ireland	Mid-Western Regional Hospital	Limerick
Ireland	Sligo General Hospital	Sligo
Ireland	The Adelaide and Meath Hospital	Tallaght
Italy	European Institute of Oncology	Milan
Malta	Sir Paul Boffa Hospital,	Floriana
Sweden	Sweden	Lund
Switzerland	Switzerland(St. Gallen)	(St. Gallen)
Switzerland	Inselspital Bern	Bern
Switzerland	Oncocare Sonnenhof-Klinik Engeriedspital	Bern
Switzerland	Hopital Cantonal Universitaire de Geneve	Geneva
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonspital	Luzern
Switzerland	Ospedale Beata Vergine	Mendrisio
Switzerland	Tumor Zentrum ZeTup St. Gallen und Chur	St. Gallen
Switzerland	Regionalspital	Thun
Turkey	Turkey(Istanbul University)	Istanbul
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Tameside General Hospital	Ashton under Lyne
United Kingdom	Centre for Cancer Research and Cell Biology at Queen's University Belfast	Belfast	Northern Ireland
United Kingdom	Royal Bolton Hospital	Bolton
United Kingdom	Royal Bournemouth Hospital	Bournemouth
United Kingdom	St Lukes Hospital	Bradford
United Kingdom	Royal Sussex County Hospital	Brighton
United Kingdom	Bristol Infirmary	Bristol
United Kingdom	Frenchay Hospital	Bristol	England
United Kingdom	Queens Hospital Burton	Burton
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Cheltenham General Hospital	Cheltenham
United Kingdom	Countess of Chester Hospital	Chester
United Kingdom	Colchester General Hospital	Colchester	England
United Kingdom	Derbyshire Royal Infirmary	Derby
United Kingdom	Ninewells Hospital	Dundee	Scotland
United Kingdom	Royal Infirmary of Edinburgh at Little France	Edinburgh	Scotland
United Kingdom	St Margaret's Hospital	Epping
United Kingdom	Royal Devon and Exeter Hospital	Exeter
United Kingdom	Frimley Park Hospital NHS Trust	Frimley
United Kingdom	Grantham & District Hospital	Grantham
United Kingdom	Conquest Hospital, The Ridge	Hastings
United Kingdom	Huddersfield Royal Infirmary	Huddersfield
United Kingdom	Castle Hill Hospital	Hull
United Kingdom	Airedale General Hospital	Keighley
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leeds St James.	Leeds
United Kingdom	Lincoln County Hospital	Lincoln
United Kingdom	Royal Liverpool University Hospital	Liverpool	England
United Kingdom	Royal Marsden Hospital	London	Please Select
United Kingdom	St. Bartholomew's Hospital	London	Please Select
United Kingdom	St. Thomas' Hospital	London	England
United Kingdom	Whittington Hospital	London	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Newcastle Upon Tyne Hospitals NHS Trust	Newcastle-Upon-Tyne	England
United Kingdom	Nottingham City Hospital	Nottingham	England
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Royal Hospital Haslar	Portsmouth
United Kingdom	Scarborough NHS Trust	Scarborough
United Kingdom	Weston Park Hospital	Sheffield
United Kingdom	Royal South Hants Hospital	Southampton	England
United Kingdom	Staffordshire General Hospital	Stafford
United Kingdom	Singleton Hospital	Swansea
United Kingdom	Treliske Royal Cornwall Hospital	Truro
United Kingdom	Clayton Hospital, Northgate	Wakefield
United Kingdom	Welwyn Garden City Hospital	Welwyn
United Kingdom	Wishaw General Hospital	Wishaw
United Kingdom	Worthing Hospital	Worthing
United Kingdom	Yeovil District Hospital	Yeovil
United Kingdom	York Hospital	York

Sponsors (2)

Lead Sponsor	Collaborator
Queen Mary University of London	Cancer Research UK

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Chile,  France,  Germany,  Hungary,  Ireland,  Italy,  Malta,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years		2 years
Secondary	To examine the effect of tamoxifen vs anastrozole on breast cancer mortality		7 years

External Links

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