Clinical trial NCT00072462: Adjuvant Tamoxifen Compared With Anastrozole in Treating Postmenopausal Women With Ductal Carcinoma In Situ
Official title: International Breast Cancer Intervention Study II (IBIS-II) (DCIS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: ductal breast carcinoma in situ
breast cancer in situ
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
First posted: 2003-11-06
Enrollment: 2980
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

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