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

Official Title: “An International Multi-Centre Study Of Tamoxifen Vs Anastrozole In Postmenopausal Women With Ductal Carcinoma In Situ (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.

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, multicenter study. Patients are stratified according to participating center. 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.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 4,000 patients will be accrued for this study within 4 years.

Intervention(s) in this Clinical Trial

• Drug: anastrozole
• Drug: tamoxifen citrate
• Procedure: adjuvant therapy

Primary Measures

• Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years
  • Safety Issue?: No

Secondary Measures

• Breast cancer mortality with median follow-up at 10 years
  • Safety Issue?: No

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
• 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 3 months unless treatment was completed more than 5 years ago
• No prior or concurrent raloxifene use lasting more than 3 months unless treatment was completed more than 5 years ago
• No other prior or concurrent selective estrogen-receptor modulator use lasting more than 3 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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Cancer Research UK Other

Overall Clinical Trial Officials and Contacts

Jack Cuzick, PhD Study Chair Cancer Research UK  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00072462

Study ID Number: CDR0000339738

ClinicalTrials.gov Identifier: NCT00072462

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database