Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid

March 13, 2024 updated by: Austrian Breast & Colorectal Cancer Study Group

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The trial is conducted as an open multi-center phase III study, in a two-factorial study design and according to Good Clinical Practice (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 Bone Mineral Density (BMD) measurements will be performed in a subgroup of patients (404 patients, enrolled in 3 centres).

Study Type

Interventional

Enrollment (Actual)

1803

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Salzburg, Austria, 5020
        • Paracelsus Medical University Salzburg - Oncology
      • Vienna, Austria, 1090
        • Medical University of Vienna, General Hospital
      • Vienna, Austria, 1020
        • Hospital BHB Vienna, Surgery
      • Vienna, Austria, 1090
        • Hospital Sanatorium Hera
      • Vienna, Austria, 1090
        • Medical University of Vienna, General Hospital, Gynaecology and Obstetrics
      • Vienna, Austria, 1090
        • Medical University Vienna, General Hospital
      • Vienna, Austria, 1130
        • State Hospital Vienna-Hietzing
      • Vienna, Austria, 1140
        • Hanusch Hospital
      • Vienna, Austria, 1160
        • Wilheminenspital, Internal Medicin I
    • Burgenland
      • Guessing, Burgenland, Austria, 7540
        • Hospital of Guessing
      • Oberpullendorf, Burgenland, Austria, 7350
        • Hospital Oberpullendorf
      • Oberwart, Burgenland, Austria, 7400
        • Hospital Oberwart
    • Carinthia
      • Klagenfurt, Carinthia, Austria, 9026
        • State Hospital Klagenfurt, Surgery
      • Klagenfurt, Carinthia, Austria, 9026
        • State Hospital Klagenfurt
      • St. Veit a. d. Glan, Carinthia, Austria, 9300
        • Hospital BHB St. Veit
      • St. Veit a. d. Glan, Carinthia, Austria, 9300
        • Ordination Dr. Wette
      • Villach, Carinthia, Austria, 9500
        • State Hospital Villach
      • Villach, Carinthia, Austria, 9504
        • Privat Hospital Villach
      • Wolfsberg, Carinthia, Austria, 9400
        • State Hospital Wolfsberg
    • Lower Austria
      • Hainburg An Der Donau, Lower Austria, Austria, 2410
        • Hospital Hainburg
      • Klosterneuburg, Lower Austria, Austria, 3400
        • Hospital Klosterneuburg, Internal Medicine
      • Krems, Lower Austria, Austria, 3500
        • Hospital Krems
      • Melk, Lower Austria, Austria, 3390
        • Hospital Melk
      • Mistelbach, Lower Austria, Austria, 2130
        • Hospital Mistelbach
      • Mödling, Lower Austria, Austria, 2340
        • Hospital Mödling
      • Neunkirchen, Lower Austria, Austria, 2620
        • Hospital Neunkirchen
      • Scheibbs, Lower Austria, Austria, 3270
        • Hospital Scheibbs
      • St. Poelten, Lower Austria, Austria, 3100
        • Hospital St. Poelten
      • Tulln, Lower Austria, Austria, 3430
        • Hospital Tulln
      • Waidhofen An Der Thaya, Lower Austria, Austria, 3830
        • Hospital Waidhofen/Thaya
      • Wiener Neustadt, Lower Austria, Austria, 2700
        • Hospital of Wiener Neustadt
    • Salzburg
      • Schwarzach, Salzburg, Austria, 5620
        • Kardinal Schwarzenberg'sches Hospital
    • Styria
      • Feldbach, Styria, Austria, 8330
        • State Hospital Feldbach
      • Graz, Styria, Austria, 8036
        • Medical University of Graz, Oncology
      • Graz, Styria, Austria, 8036
        • Gynaegological Medical University of Graz
      • Leoben, Styria, Austria, 8700
        • State Hospital Leoben
      • Rottenmann, Styria, Austria, 8786
        • State Hospital Rottenmann
      • Weiz, Styria, Austria, 8160
        • Brustgesundheitszentrum-Süd Institut / Dr. Thiel
    • Tyrol
      • Hall in Tirol, Tyrol, Austria, 6060
        • District Hospital Hall in Tirol
      • Innsbruck, Tyrol, Austria, 6020
        • Gynaegological Medical University Innsbruck
      • Kufstein, Tyrol, Austria, 6330
        • District Hospital Kufstein
      • Lienz, Tyrol, Austria, 9900
        • District Hospital Lienz
      • Zams, Tyrol, Austria, 6511
        • Hospital St. Vinzenz
    • Upper Austria
      • Bad Ischl, Upper Austria, Austria, 4820
        • State Hospital Bad Ischl
      • Freistadt, Upper Austria, Austria, 4240
        • State Hospital Freistadt
      • Gmunden, Upper Austria, Austria, 4810
        • State Hospital Gmunden
      • Kirchdorf, Upper Austria, Austria, 4560
        • State Hospital Kirchdorf
      • Linz, Upper Austria, Austria, 4020
        • General Hospital Linz
      • Linz, Upper Austria, Austria, 4020
        • Hospital BHB Linz
      • Linz, Upper Austria, Austria, 4010
        • Hospital BHS Linz
      • Linz, Upper Austria, Austria, 4010
        • Hospital Elisabethinen Linz
      • Linz, Upper Austria, Austria, 4020
        • Ordination Dr. Pöstlberger
      • Ried, Upper Austria, Austria, 4910
        • Hospital BHS Ried
      • Rohrbach, Upper Austria, Austria, 4150
        • State Hospital Rohrbach
      • Schärding, Upper Austria, Austria, 4780
        • State Hospital Schärding
      • Steyr, Upper Austria, Austria, 4400
        • State Hospital Steyr
      • Voecklabruck, Upper Austria, Austria, 4840
        • State Hospital Voecklabruck, Internal Medicine
      • Voecklabruck, Upper Austria, Austria, 4840
        • State Hospital Voecklabruck, Surgery Dept.
      • Wels, Upper Austria, Austria, 4600
        • Klinikum Wels-Grieskirchen
    • Vorarlberg
      • Bregenz, Vorarlberg, Austria, 6900
        • State Hospital Bregenz
      • Dornbirn, Vorarlberg, Austria, 6850
        • State Hospital of Dornbirn
      • Feldkirch, Vorarlberg, Austria, 6807
        • State Hospital Feldkirch
  • Germany
      • Berlin, Germany, 10967
        • Vivantes-Klinikum Friedrichshain
    • Baden-Wuerttemberg
      • Freiburg, Baden-Wuerttemberg, Germany, 79106
        • Practice Dr. Marschner
      • Ulm, Baden-Wuerttemberg, Germany, 89073
        • Medical Care Center
    • Bavaria
      • Amberg, Bavaria, Germany, 92224
        • Klinikum St. Marien
      • Muenchen, Bavaria, Germany, 80637
        • Frauenklinik vom Roten Kreuz
      • Munich, Bavaria, Germany, 80337
        • Med. University of Munich
    • Hesse
      • Kassel, Hesse, Germany, 34117
        • Elisabeth-Hospital
    • Lower Saxony
      • Oldenburg, Lower Saxony, Germany, 26121
        • Internal-haematological Practice Oldenburg
    • Saxony
      • Gifhorn, Saxony, Germany, 38518
        • General Hospital Gifhorn
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105
        • Medical University Kiel

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 59 years (Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: AZ (Arimidex+Zoledronate)
Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid)
Drug: anastrozole
1 mg/d
Other Names:
  • Arimidex
Drug: zoledronic acid
4 mg q6m
Other Names:
  • Zoledronate, Zometa
Other: goserelin
3.6 mg goserelin subcutaneously every 28 days
Active Comparator: TZ (Tamoxifen+Zoledronate)
Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid)
Drug: zoledronic acid
4 mg q6m
Other Names:
  • Zoledronate, Zometa
Drug: tamoxifen
20 mg/d
Other Names:
  • Nolvadex
Other: goserelin
3.6 mg goserelin subcutaneously every 28 days
Active Comparator: AC (Arimidex Control)
Study Drug Arimidex (Anastrozole)
Drug: anastrozole
1 mg/d
Other Names:
  • Arimidex
Other: goserelin
3.6 mg goserelin subcutaneously every 28 days
Active Comparator: TC (Tamoxifen Control)
Study Drug Nolvadex (Tamoxifen)
Drug: tamoxifen
20 mg/d
Other Names:
  • Nolvadex
Other: goserelin
3.6 mg goserelin subcutaneously every 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of Anastrozole vs Tamoxifen in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Disease-free Survival (DFS)
Time Frame: Time from randomization to the analysis data cut-off date when 124 DFS events had occurred. On the analysis data cut-off date, maximum time on study per patient was 102 months.
DFS is defined as time from randomization to first occurrence of a local, regional, or distant recurrence, second primary carcinoma (including contralateral breast cancer), or death from any cause
Time from randomization to the analysis data cut-off date when 124 DFS events had occurred. On the analysis data cut-off date, maximum time on study per patient was 102 months.
Comparison of Zoledronate vs no Zoledronate in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Disease-free Survival (DFS)
Time Frame: Time from randomization to the analysis data cut-off date when 124 DFS events had occurred. On the analysis data cut-off date, maximum time on study per patient was 102 months.
DFS is defined as time from randomization to first occurrence of a local, regional, or distant recurrence, second primary carcinoma (including contralateral breast cancer), or death from any cause
Time from randomization to the analysis data cut-off date when 124 DFS events had occurred. On the analysis data cut-off date, maximum time on study per patient was 102 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of Anastrozole vs Tamoxifen in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Recurrence-free Survival (RFS)
Time Frame: Time from randomization to the analysis data cut-off date when 124 DFS events had occurred. On the analysis data cut-off date, maximum time on study per patient was 102 months.
RFS is defined as time from randomization to first occurrence of a local, regional, or distant recurrence, second primary carcinoma (including contralateral breast cancer), or death from breast cancer
Time from randomization to the analysis data cut-off date when 124 DFS events had occurred. On the analysis data cut-off date, maximum time on study per patient was 102 months.
Comparison of Zoledronate vs no Zoledronate in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Recurrence-free Survival (RFS)
Time Frame: Time from randomization to the analysis data cut-off date when 124 DFS events had occurred. On the analysis data cut-off date, maximum time on study per patient was 102 months.
RFS is defined as time from randomization to first occurrence of a local, regional, or distant recurrence, second primary carcinoma (including contralateral breast cancer), or death from breast cancer
Time from randomization to the analysis data cut-off date when 124 DFS events had occurred. On the analysis data cut-off date, maximum time on study per patient was 102 months.
Comparison of Anastrozole vs Tamoxifen in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Overall Survival (OS)
Time Frame: Time from randomization to the analysis data cut-off date when 124 DFS events had occurred. On the analysis data cut-off date, maximum time on study per patient was 102 months.
OS is defined as time from randomization to death from any cause
Time from randomization to the analysis data cut-off date when 124 DFS events had occurred. On the analysis data cut-off date, maximum time on study per patient was 102 months.
Comparison of Zoledronate vs no Zoledronate in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Overall Survival (OS)
Time Frame: Time from randomization to the analysis data cut-off date when 124 DFS events had occurred. On the analysis data cut-off date, maximum time on study per patient was 102 months.
OS is defined as time from randomization to death from any cause
Time from randomization to the analysis data cut-off date when 124 DFS events had occurred. On the analysis data cut-off date, maximum time on study per patient was 102 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Austrian Breast & Colorectal Cancer Study Group

Collaborators

AstraZeneca
Novartis Pharmaceuticals

Investigators

  • Principal Investigator: Raimund Jakesz, MD, Austrian Breast & Colorectal Cancer Study Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 1999

Primary Completion (Actual)

March 27, 2008

Study Completion (Actual)

June 26, 2018

Study Registration Dates

First Submitted

February 23, 2006

First Submitted That Met QC Criteria

February 23, 2006

First Posted (Estimated)

February 24, 2006

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 13, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ABCSG-12
  • CZOL 446 1B 01 (Other Identifier: Novartis)
  • Zol-A-01 (Other Identifier: Novartis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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