Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT00295646
- Lead Sponsor
- Austrian Breast & Colorectal Cancer Study Group
- Brief Summary
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.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 1803
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TC (Tamoxifen Control) goserelin Study Drug Nolvadex (Tamoxifen) AZ (Arimidex+Zoledronate) goserelin Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid) AC (Arimidex Control) goserelin Study Drug Arimidex (Anastrozole) TZ (Tamoxifen+Zoledronate) goserelin Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid) AZ (Arimidex+Zoledronate) anastrozole Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid) AZ (Arimidex+Zoledronate) zoledronic acid Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid) TZ (Tamoxifen+Zoledronate) tamoxifen Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid) TZ (Tamoxifen+Zoledronate) zoledronic acid Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid) AC (Arimidex Control) anastrozole Study Drug Arimidex (Anastrozole) TC (Tamoxifen Control) tamoxifen Study Drug Nolvadex (Tamoxifen)
- Primary Outcome Measures
Name Time Method Comparison of Zoledronate vs no Zoledronate in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Disease-free Survival (DFS) 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
Comparison of Anastrozole vs Tamoxifen in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Disease-free Survival (DFS) 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
- Secondary Outcome Measures
Name Time Method Comparison of Zoledronate vs no Zoledronate in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Recurrence-free Survival (RFS) 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
Comparison of Anastrozole vs Tamoxifen in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Recurrence-free Survival (RFS) 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
Comparison of Anastrozole vs Tamoxifen in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Overall Survival (OS) 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
Comparison of Zoledronate vs no Zoledronate in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Overall Survival (OS) 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
Trial Locations
- Locations (72)
State Hospital Klagenfurt, Surgery
🇦🇹Klagenfurt, Carinthia, Austria
State Hospital Klagenfurt
🇦🇹Klagenfurt, Carinthia, Austria
Medical University Kiel
🇩🇪Kiel, Schleswig-Holstein, Germany
Hospital BHB St. Veit
🇦🇹St. Veit a. d. Glan, Carinthia, Austria
Hospital Krems
🇦🇹Krems, Lower Austria, Austria
District Hospital Kufstein
🇦🇹Kufstein, Tyrol, Austria
General Hospital Linz
🇦🇹Linz, Upper Austria, Austria
Hospital BHS Ried
🇦🇹Ried, Upper Austria, Austria
Hospital Oberwart
🇦🇹Oberwart, Burgenland, Austria
Frauenklinik vom Roten Kreuz
🇩🇪Muenchen, Bavaria, Germany
Hospital Mistelbach
🇦🇹Mistelbach, Lower Austria, Austria
Gynaegological Medical University Innsbruck
🇦🇹Innsbruck, Tyrol, Austria
Brustgesundheitszentrum-Süd Institut / Dr. Thiel
🇦🇹Weiz, Styria, Austria
Hospital of Guessing
🇦🇹Guessing, Burgenland, Austria
State Hospital Leoben
🇦🇹Leoben, Styria, Austria
Hospital St. Poelten
🇦🇹St. Poelten, Lower Austria, Austria
Klinikum Wels-Grieskirchen
🇦🇹Wels, Upper Austria, Austria
Hospital Klosterneuburg, Internal Medicine
🇦🇹Klosterneuburg, Lower Austria, Austria
Hospital Neunkirchen
🇦🇹Neunkirchen, Lower Austria, Austria
District Hospital Hall in Tirol
🇦🇹Hall in Tirol, Tyrol, Austria
State Hospital Schärding
🇦🇹Schärding, Upper Austria, Austria
State Hospital Rottenmann
🇦🇹Rottenmann, Styria, Austria
Elisabeth-Hospital
🇩🇪Kassel, Hesse, Germany
Hospital Oberpullendorf
🇦🇹Oberpullendorf, Burgenland, Austria
Ordination Dr. Wette
🇦🇹St. Veit a. d. Glan, Carinthia, Austria
State Hospital Villach
🇦🇹Villach, Carinthia, Austria
Privat Hospital Villach
🇦🇹Villach, Carinthia, Austria
State Hospital Wolfsberg
🇦🇹Wolfsberg, Carinthia, Austria
Hospital Hainburg
🇦🇹Hainburg An Der Donau, Lower Austria, Austria
Hospital Melk
🇦🇹Melk, Lower Austria, Austria
Hospital Mödling
🇦🇹Mödling, Lower Austria, Austria
Hospital Scheibbs
🇦🇹Scheibbs, Lower Austria, Austria
Hospital Tulln
🇦🇹Tulln, Lower Austria, Austria
Hospital Waidhofen/Thaya
🇦🇹Waidhofen An Der Thaya, Lower Austria, Austria
Hospital of Wiener Neustadt
🇦🇹Wiener Neustadt, Lower Austria, Austria
Kardinal Schwarzenberg'sches Hospital
🇦🇹Schwarzach, Salzburg, Austria
State Hospital Feldbach
🇦🇹Feldbach, Styria, Austria
Gynaegological Medical University of Graz
🇦🇹Graz, Styria, Austria
Medical University of Graz, Oncology
🇦🇹Graz, Styria, Austria
District Hospital Lienz
🇦🇹Lienz, Tyrol, Austria
Hospital St. Vinzenz
🇦🇹Zams, Tyrol, Austria
State Hospital Freistadt
🇦🇹Freistadt, Upper Austria, Austria
State Hospital Bad Ischl
🇦🇹Bad Ischl, Upper Austria, Austria
State Hospital Gmunden
🇦🇹Gmunden, Upper Austria, Austria
State Hospital Kirchdorf
🇦🇹Kirchdorf, Upper Austria, Austria
Hospital BHS Linz
🇦🇹Linz, Upper Austria, Austria
Hospital Elisabethinen Linz
🇦🇹Linz, Upper Austria, Austria
Hospital BHB Linz
🇦🇹Linz, Upper Austria, Austria
State Hospital Rohrbach
🇦🇹Rohrbach, Upper Austria, Austria
State Hospital Steyr
🇦🇹Steyr, Upper Austria, Austria
State Hospital Voecklabruck, Internal Medicine
🇦🇹Voecklabruck, Upper Austria, Austria
State Hospital Voecklabruck, Surgery Dept.
🇦🇹Voecklabruck, Upper Austria, Austria
State Hospital Bregenz
🇦🇹Bregenz, Vorarlberg, Austria
State Hospital of Dornbirn
🇦🇹Dornbirn, Vorarlberg, Austria
State Hospital Feldkirch
🇦🇹Feldkirch, Vorarlberg, Austria
Paracelsus Medical University Salzburg - Oncology
🇦🇹Salzburg, Austria
Hospital BHB Vienna, Surgery
🇦🇹Vienna, Austria
Hospital Sanatorium Hera
🇦🇹Vienna, Austria
Medical University of Vienna, General Hospital, Gynaecology and Obstetrics
🇦🇹Vienna, Austria
Medical University of Vienna, General Hospital
🇦🇹Vienna, Austria
Medical University Vienna, General Hospital
🇦🇹Vienna, Austria
State Hospital Vienna-Hietzing
🇦🇹Vienna, Austria
Hanusch Hospital
🇦🇹Vienna, Austria
Wilheminenspital, Internal Medicin I
🇦🇹Vienna, Austria
Practice Dr. Marschner
🇩🇪Freiburg, Baden-Wuerttemberg, Germany
Medical Care Center
🇩🇪Ulm, Baden-Wuerttemberg, Germany
Klinikum St. Marien
🇩🇪Amberg, Bavaria, Germany
Med. University of Munich
🇩🇪Munich, Bavaria, Germany
Internal-haematological Practice Oldenburg
🇩🇪Oldenburg, Lower Saxony, Germany
General Hospital Gifhorn
🇩🇪Gifhorn, Saxony, Germany
Vivantes-Klinikum Friedrichshain
🇩🇪Berlin, Germany
Ordination Dr. Pöstlberger
🇦🇹Linz, Upper Austria, Austria