Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid

Condition(s) targeted: Breast Cancer

Intervention: tamoxifen (Drug); anastrozole (Drug); zoledronic acid (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Austrian Breast & Colorectal Cancer Study Group

Official(s) and/or principal investigator(s):
Raimund Jakesz, MD, Principal Investigator, Affiliation: ABCSG

The primary objective of the comparison between tamoxifen and anastrozole is, first, to compare disease-free survival and overall survival in 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.

Official title: Tamoxifen Vs. Anastrozole, Alone or in Combination With Zoledronic Acid, in Premenopausal, Hormone Receptor-Positive Breast Cancer Patients (Stage I, II)

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

Primary outcome:

To compare overall and recurrence-free survival between tamoxifen and anastrozole

To compare bone loss reduction/prevention between zoledronic acid and no zoledronic acid

Secondary outcome:

To compare overall and recurrence-free survival between zoledronic acid and no zoledronic acid given with tamoxifen or anastrozole

To compare bone metastasis development with zoledronic acid vs no zoledronic acid

Detailed description: The primary objective of the comparison between tamoxifen and anastrozole is, first, to compare disease-free survival and overall survival in 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.

The secondary objective is to assess whether zoledronate added to standard adjuvant treatment can increase disease-free survival and OS in patients with non-metastatic breast cancer as compared to those not receiving zoledronate. To explore the effect of zoledronate on the development of bone metastases in patients with primary breast cancer as compared to those patients not treated with zoledronate.

A total of 1. 800 patients will be enrolled in 4 arms. The dose of zoledronat will be administered every 6 months as an 4mg bolus injection (15 minutes of short infusion) over a treatment period of 3 years. In a subgroup of patients (400 patients, 90 per arm, enrolled in 3 centres) bone mineral density (BMD) is going to be measured. This measurement is the primary endpoint for the bisphosphonate zoledronate with respect to prevention of bone loss due to complete estrogen supression in this patient population. BMD will be measured by Dual X-ray Absorptiometry (DXA).

Minimum age: 19 Years. Maximum age: 59 Years. Gender(s): Female.

Criteria:

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

Paracelsus Medical University Salzburg - Oncology, Salzburg 5020, Austria

Medical University of Vienna, General Hospital, Vienna 1090, Austria

Hanusch Hospital, Vienna 1140, Austria

Medical University of Vienna, General Hospital, Vienna 1090, Austria

Medical University Vienna, General Hospital, Vienna 1090, Austria

State Hospital Vienna-Lainz, Vienna 1130, Austria

Medical University of Vienna, General Hospital, Gynaecology and Obstetrics, Vienna 1090, Austria

Medical University of Vienna, Gynaecology and Obstetrics II, Vienna 1090, Austria

Privat Hospital Sanatorium Hera, Vienna 1090, Austria

Wilheminenspital, Internal Medicin I, Vienna 1160, Austria

Wilhelminenspital, Gynaecology, Vienna 1160, Austria

Vivantes-Klinikum Friedrichshain, Berlin 10967, Germany

Practice Dr. Marschner, Freiburg, Baden-Wuerttemberg 79106, Germany

Medical Care Center, Ulm, Baden-Wuerttemberg 89073, Germany

Frauenklinik vom Roten Kreuz, Muenchen, Bavaria 80637, Germany

Med. University of Munich, Munich, Bavaria 80337, Germany

Klinikum St. Marien, Amberg, Bavaria 92224, Germany

Hospital Oberwart, Oberwart, Burgenland 7400, Austria

Hospital of Guessing, Guessing, Burgenland 7540, Austria

Hospital Oberpullendorf, Oberpullendorf, Burgenland 7350, Austria

State Hospital Klagenfurt, Surgery, Klagenfurt, Carinthia 9026, Austria

State Hospital Wolfsberg, Wolfsberg, Carinthia 9400, Austria

State Hospital Klagenfurt, Klagenfurt, Carinthia 9026, Austria

Hospital BHB St. Veit, St. Veit a. d. Glan, Carinthia 9300, Austria

Ordination Dr. Wette, St. Veit a. d. Glan, Carinthia 9300, Austria

State Hospital Villach, Villach, Carinthia 9500, Austria

Privat Hospital Villach, Villach, Carinthia 9504, Austria

Elisabeth-Hospital, Kassel, Hesse 34117, Germany

Hospital Krems, Krems, Lower Austria 3500, Austria

Hospital of Wiener Neustadt, Wiener Neustadt, Lower Austria 2700, Austria

Hospital Gmuend, Gmuend, Lower Austria 3952, Austria

Hospital Hainburg, Hainburg, Lower Austria 2410, Austria

Hospital Klosterneuburg, Internal Medicine, Klosterneuburg, Lower Austria 3400, Austria

Hospital Melk, Melk, Lower Austria 3390, Austria

Hospital Mistelbach, Mistelbach, Lower Austria 2130, Austria

Hospital Moedling, Moedling, Lower Austria 2340, Austria

Hospital Scheibbs, Scheibbs, Lower Austria 3270, Austria

Hospital St. Poelten, St. Poelten, Lower Austria 3100, Austria

Hospital Tulln, Tulln, Lower Austria 3430, Austria

Hospital Waidhofen/Thaya, Waidhofen a. d. Thaya, Lower Austria 3830, Austria

Hospital Neunkirchen, Neunkirchen, Lower Austria 2620, Austria

Internal-haematological Practice Oldenburg, Oldenburg, Lower Saxony 26121, Germany

Kardinal Schwarzenberg`sches Hospital, Schwarzach, Salzburg 5620, Austria

General Hospital Gifhorn, Gifhorn, Saxony 38518, Germany

Medical University Kiel, Kiel, Schleswig-Holstein 24105, Germany

Gynaegological Medical University of Graz, Graz, Styria 8036, Austria

Medical University of Graz, Oncology, Graz, Styria 8036, Austria

State Hospital Leoben, Leoben, Styria 8700, Austria

State Hospital Feldbach, Feldbach, Styria 8330, Austria

Breast Ordination Dr. Thiel, Graz, Styria 8042, Austria

State Hospital Leoben, Leoben, Styria 8700, Austria

State Hospital Rottenmann, Rottenmann, Styria 8786, Austria

District Hospital Kufstein, Kufstein, Tyrol 6330, Austria

Gynaegological Medical University Innsbruck, Innsbruck, Tyrol 6020, Austria

Hospital St. Vinzenz, Zams, Tyrol 6511, Austria

District Hospital Hall in Tirol, Hall in Tirol, Tyrol 6060, Austria

District Hospital Lienz, Lienz, Tyrol 9900, Austria

General Hospital Linz, Linz, Upper Austria 4020, Austria

Hospital BHS Linz, Linz, Upper Austria 4010, Austria

Hospital Kreuzschwestern Wels, Wels, Upper Austria 4600, Austria

State Hospital Steyr, Steyr, Upper Austria 4400, Austria

State Hospital Bad Ischl, Bad Ischl, Upper Austria 4820, Austria

State Hospital Freistadt, Freistadt, Upper Austria 4240, Austria

State Hospital Gmunden, Gmunden, Upper Austria 4810, Austria

State Hospital Kirchdorf, Kirchdorf, Upper Austria 4560, Austria

Hospital BHB Linz, Linz, Upper Austria 4020, Austria

Hospital Elisabethinen Linz, Linz, Upper Austria 4010, Austria

Ordination Dr. Tausch, Linz, Upper Austria 4020, Austria

Hospital BHS Ried, Ried, Upper Austria 4910, Austria

State Hospital Rohrbach, Rohrbach, Upper Austria 4150, Austria

State Hospital Schaerding, Schaerding, Upper Austria 4780, Austria

State Hospital Voecklabruck, Internal Medicine, Voecklabruck, Upper Austria 4840, Austria

State Hospital Feldkirch, Feldkirch, Vorarlberg 6807, Austria

State Hospital Bregenz, Bregenz, Vorarlberg 6900, Austria

State Hospital of Dornbirn, Dornbirn, Vorarlberg 6850, Austria

Starting date: June 1999
Last updated: August 29, 2006