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

• ClinicalTrials.gov Identifier: NCT00072462
• Recruitment Status: Completed
• First Posted: November 6, 2003
• Last Update Posted: October 6, 2021
• Sponsor: Queen Mary University of London
• Collaborator: Cancer Research UK
• Information provided by (Responsible Party): Queen Mary University of London

Tracking Information

• First Submitted Date: November 4, 2003
• First Posted Date: November 6, 2003
• Last Update Posted Date: October 6, 2021
• Study Start Date: September 2003
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 28, 2012): Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years [ Time Frame: 2 years ]
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures (submitted: March 28, 2012): To examine the effect of tamoxifen vs anastrozole on breast cancer mortality [ Time Frame: 7 years ]
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: tamoxifen citrate
  Tamoxifen 20mg + Anastrozole placebo
  Other Name: Nolvadex
• Drug: Anastrozole
  Anastrozole 1mg + Tamoxifen placebo
  Other Name: Arimidex

Study Arms

• Active Comparator: Anastrozole
  Intervention: Drug: Anastrozole
• Active Comparator: Tamoxifen
  Intervention: Drug: tamoxifen citrate

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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 29, 2012): 2980
• Original Enrollment: Not Provided
• Actual Study Completion Date: May 31, 2021
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 40 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Chile, France, Germany, Hungary, Ireland, Italy, Malta, Sweden, Switzerland, Turkey, United Kingdom
• Removed Location Countries: Finland

Administrative Information

• NCT Number: NCT00072462
• Other Study ID Numbers: ISRCTN37546358; EU-20226; BIG-5-02; IBCSG-31-03-DCIS; ISRCTN31488319
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Queen Mary University of London
• 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

• PRS Account: Queen Mary University of London
• Verification Date: September 2021