Official Title: “Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid, in Premenopausal, Hormone Receptor-Positive Breast Cancer Patients (Stage I, II)”

The primary objective is, first, the comparison of tamoxifen and anastrozole and, second, the comparison of zoledronate added to standard adjuvant therapy with controls according to disease-free survival (DFS) in premenopausal patients with non-metastatic breast cancer treated with tamoxifen or anastrozole. To assess whether zoledronate added to standard adjuvant therapy can decrease or even prevent bone loss in patients treated with hormonal blockade combined with an antiestrogen or aromatase inhibitor.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: May 2013

The trial is conducted as an open multi-center phase III study, in a two-factorial study design and according to GCP guidelines. Patients will be randomly assigned to a total of 4 study groups in a 1:1:1:1 assignment ratio. Several stratification criteria will be used in order to ensure balanced distribution of known risk factors.

A total of 1.803 patients will be enrolled in 4 arms. Patients will either be treated with anastrozole (1mg daily for 3 years) or tamoxifen (20mg daily for 3 years), and will additionally receive either zoledronate (8mg q4 weeks for 3 years) or no zoledronate (arm A:

Nolvadex alone; arm B: Nolvadex plus zoledronate; arm C: Arimidex alone; arm D: Arimidex plus zoledronate).

Zoledronate will be administered by i.v. injection at a dose of 4 mg/month for the treatment period of 3 years. Five BMD measurements will be performed in a subgroup of patients (404 patients, enrolled in 3 centres).

Intervention(s) in this Clinical Trial

• Drug: tamoxifen
  • 20 mg/d
• Drug: anastrozole
  • 1 mg/d
• Drug: zoledronic acid
  • 4 mg q6m

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: AZ
  • Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate)
• Active Comparator: TZ
  • Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate)
• Active Comparator: AC
  • Study Drug Arimidex (Anastrozole)
• Active Comparator: TC
  • Study Drug Nolvadex (Tamoxifen)

Primary Measures

• Comparison of tamoxifen with anastrozole in premenopausal patients with non-metastatic breast cancer and comparison of a subgroup additionally treated with zoledronate to a control subgroup without receiving zoledronate according to DFS.
  • Time Frame: 28.05.2008
    Safety Issue?: No

Secondary Measures

• For the assessment of the recurrence free survival (RFS) patients receiving tamoxifen will be compared to patients receiving anastrozole and patients receiving zoledronate will be compared to controls, respectively.
  • Time Frame: 28.05.2008
    Safety Issue?: No
• For the assessment of the overall survival (OS) patients receiving tamoxifen will be compared to patients receiving anastrozole and patients receiving zoledronate will be compared to controls, respectively.
  • Time Frame: 28.05.2008
    Safety Issue?: No
• The objective is to assess whether zoledronate added to standard adjuvant therapy can decrease or even prevent bone loss in patients treated with hormonal blockade combined with an anti-estrogen or aromatase inhibitor (AI).
  • Time Frame: 28.05.2008
    Safety Issue?: No
• Adverse and severe adverse events will be listed for all therapy subgroups "anastrozole / zoledronate" (AZ), "anastrozole / zoledronate control" (AC), "tamoxifen / zoledronate" (TZ), "tamoxifen / zoledronate control" (TC).
  • Time Frame: 28.05.2008
    Safety Issue?: Yes

Inclusion Criteria:

• Premenopausal, hormone receptor-positive patient
• Histologically verified (minimally) invasive breast cancer, local radical treatment
• 0-9 involved axillary lymph nodes (≥ 10 histologically examined nodes)
• Tumor stage: pT1b-3, yT0 or yT1a

Exclusion Criteria:

• T1a, T4d, yT4; M1
• Previous breast tumor irradiation
• Previous or concurrent chemotherapy (except for preoperative chemotherapy)
• Serum creatinine > 1.5 x UNL or creatinine clearance < 60 ml/min

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 19 Years

Maximum Age for this Clinical Trial: 59 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Austrian Breast & Colorectal Cancer Study Group

Overall Clinical Trial Officials and Contacts

Raimund Jakesz, MD Principal Investigator ABCSG  

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00295646

Study ID Number: ABCSG-12

ClinicalTrials.gov Identifier: NCT00295646

Health Authority: Austria: Federal Ministry for Health and Women