Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid

NCT00295646 | Completed Phase 3 Results DMC

• 3 other identifiers: ABCSG-12CZOL 446 1B 01Zol-A-01
• Study Type: interventional
• Target: 1,803
• Locations: 2 countries
• Sites: 72

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.

Conditions

Breast Cancer

Keywords

Austrian Breast & Colorectal Cancer Study Group (ABCSG); 12; Phase 3; breast cancer; anastrozole; tamoxifen; zoledronic acid; premenopausal; hormone receptor-positive; Stage I; Stage II; bone mineral density; BMD; bisphosphonate; zoledronate

Outcome Measures

Primary Outcomes (2)

• Comparison of Anastrozole vs Tamoxifen in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Disease-free Survival (DFS)

  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)

  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 Outcomes (4)

• 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.

• 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.

• 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.

• 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.

Study Arms (4)

AZ (Arimidex+Zoledronate)

ACTIVE COMPARATOR

Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid)

Drug: anastrozole; Drug: zoledronic acid; Other: goserelin

TZ (Tamoxifen+Zoledronate)

ACTIVE COMPARATOR

Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid)

Drug: tamoxifen; Drug: zoledronic acid; Other: goserelin

AC (Arimidex Control)

ACTIVE COMPARATOR

Study Drug Arimidex (Anastrozole)

Drug: anastrozole; Other: goserelin

TC (Tamoxifen Control)

ACTIVE COMPARATOR

Study Drug Nolvadex (Tamoxifen)

Drug: tamoxifen; Other: goserelin

Interventions

tamoxifen DRUG

20 mg/d

Also known as: Nolvadex

TC (Tamoxifen Control); TZ (Tamoxifen+Zoledronate)

anastrozole DRUG

1 mg/d

Also known as: Arimidex

AC (Arimidex Control); AZ (Arimidex+Zoledronate)

zoledronic acid DRUG

4 mg q6m

Also known as: Zoledronate, Zometa

AZ (Arimidex+Zoledronate); TZ (Tamoxifen+Zoledronate)

goserelin OTHER

3.6 mg goserelin subcutaneously every 28 days

AC (Arimidex Control); AZ (Arimidex+Zoledronate); TC (Tamoxifen Control); TZ (Tamoxifen+Zoledronate)

Eligibility Criteria

• Age: 19 Years - 59 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Austrian Breast & Colorectal Cancer Study Group: lead
• AstraZeneca: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (72)

Hospital of Guessing

Güssing, Burgenland, 7540, Austria

Location

Hospital Oberpullendorf

Oberpullendorf, Burgenland, 7350, Austria

Location

Hospital Oberwart

Oberwart, Burgenland, 7400, Austria

Location

State Hospital Klagenfurt, Surgery

Klagenfurt, Carinthia, 9026, Austria

Location

State Hospital Klagenfurt

Klagenfurt, Carinthia, 9026, Austria

Location

Hospital BHB St. Veit

Saint Veit A. D. Glan, Carinthia, 9300, Austria

Location

Ordination Dr. Wette

Saint Veit A. D. Glan, Carinthia, 9300, Austria

Location

State Hospital Villach

Villach, Carinthia, 9500, Austria

Location

Privat Hospital Villach

Villach, Carinthia, 9504, Austria

Location

State Hospital Wolfsberg

Wolfsberg, Carinthia, 9400, Austria

Location

Hospital Hainburg

Hainburg an der Donau, Lower Austria, 2410, Austria

Location

Hospital Klosterneuburg, Internal Medicine

Klosterneuburg, Lower Austria, 3400, Austria

Location

Hospital Krems

Krems, Lower Austria, 3500, Austria

Location

Hospital Melk

Melk, Lower Austria, 3390, Austria

Location

Hospital Mistelbach

Mistelbach, Lower Austria, 2130, Austria

Location

Hospital Mödling

Mödling, Lower Austria, 2340, Austria

Location

Hospital Neunkirchen

Neunkirchen, Lower Austria, 2620, Austria

Location

Hospital St. Poelten

Sankt Pölten, Lower Austria, 3100, Austria

Location

Hospital Scheibbs

Scheibbs, Lower Austria, 3270, Austria

Location

Hospital Tulln

Tulln, Lower Austria, 3430, Austria

Location

Hospital Waidhofen/Thaya

Waidhofen an der Thaya, Lower Austria, 3830, Austria

Location

Hospital of Wiener Neustadt

Wiener Neustadt, Lower Austria, 2700, Austria

Location

Kardinal Schwarzenberg'sches Hospital

Schwarzach, Salzburg, 5620, Austria

Location

State Hospital Feldbach

Feldbach, Styria, 8330, Austria

Location

Gynaegological Medical University of Graz

Graz, Styria, 8036, Austria

Location

Medical University of Graz, Oncology

Graz, Styria, 8036, Austria

Location

State Hospital Leoben

Leoben, Styria, 8700, Austria

Location

State Hospital Rottenmann

Rottenmann, Styria, 8786, Austria

Location

Brustgesundheitszentrum-Süd Institut / Dr. Thiel

Weiz, Styria, 8160, Austria

Location

District Hospital Hall in Tirol

Hall in Tirol, Tyrol, 6060, Austria

Location

Gynaegological Medical University Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

District Hospital Kufstein

Kufstein, Tyrol, 6330, Austria

Location

District Hospital Lienz

Lienz, Tyrol, 9900, Austria

Location

Hospital St. Vinzenz

Zams, Tyrol, 6511, Austria

Location

State Hospital Bad Ischl

Bad Ischl, Upper Austria, 4820, Austria

Location

State Hospital Freistadt

Freistadt, Upper Austria, 4240, Austria

Location

State Hospital Gmunden

Gmunden, Upper Austria, 4810, Austria

Location

State Hospital Kirchdorf

Kirchdorf, Upper Austria, 4560, Austria

Location

Hospital BHS Linz

Linz, Upper Austria, 4010, Austria

Location

Hospital Elisabethinen Linz

Linz, Upper Austria, 4010, Austria

Location

General Hospital Linz

Linz, Upper Austria, 4020, Austria

Location

Hospital BHB Linz

Linz, Upper Austria, 4020, Austria

Location

Ordination Dr. Pöstlberger

Linz, Upper Austria, 4020, Austria

Location

Hospital BHS Ried

Ried, Upper Austria, 4910, Austria

Location

State Hospital Rohrbach

Rohrbach, Upper Austria, 4150, Austria

Location

State Hospital Schärding

Schärding, Upper Austria, 4780, Austria

Location

State Hospital Steyr

Steyr, Upper Austria, 4400, Austria

Location

State Hospital Voecklabruck, Internal Medicine

Vöcklabruck, Upper Austria, 4840, Austria

Location

State Hospital Voecklabruck, Surgery Dept.

Vöcklabruck, Upper Austria, 4840, Austria

Location

Klinikum Wels-Grieskirchen

Wels, Upper Austria, 4600, Austria

Location

State Hospital Bregenz

Bregenz, Vorarlberg, 6900, Austria

Location

State Hospital of Dornbirn

Dornbirn, Vorarlberg, 6850, Austria

Location

State Hospital Feldkirch

Feldkirch, Vorarlberg, 6807, Austria

Location

Paracelsus Medical University Salzburg - Oncology

Salzburg, 5020, Austria

Location

Hospital BHB Vienna, Surgery

Vienna, 1020, Austria

Location

Hospital Sanatorium Hera

Vienna, 1090, Austria

Location

Medical University of Vienna, General Hospital, Gynaecology and Obstetrics

Vienna, 1090, Austria

Location

Medical University of Vienna, General Hospital

Vienna, 1090, Austria

Location

Medical University Vienna, General Hospital

Vienna, 1090, Austria

Location

State Hospital Vienna-Hietzing

Vienna, 1130, Austria

Location

Hanusch Hospital

Vienna, 1140, Austria

Location

Wilheminenspital, Internal Medicin I

Vienna, 1160, Austria

Location

Practice Dr. Marschner

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Medical Care Center

Ulm, Baden-Wurttemberg, 89073, Germany

Location

Klinikum St. Marien

Amberg, Bavaria, 92224, Germany

Location

Med. University of Munich

Munich, Bavaria, 80337, Germany

Location

Frauenklinik vom Roten Kreuz

Munich, Bavaria, 80637, Germany

Location

Elisabeth-Hospital

Kassel, Hesse, 34117, Germany

Location

Internal-haematological Practice Oldenburg

Oldenburg, Lower Saxony, 26121, Germany

Location

General Hospital Gifhorn

Gifhorn, Saxony, 38518, Germany

Location

Medical University Kiel

Kiel, Schleswig-Holstein, 24105, Germany

Location

Vivantes-Klinikum Friedrichshain

Berlin, 10967, Germany

Location

Related Publications (16)

• Gnant M, Mlineritsch B, Luschin-Ebengreuth G, Kainberger F, Kassmann H, Piswanger-Solkner JC, Seifert M, Ploner F, Menzel C, Dubsky P, Fitzal F, Bjelic-Radisic V, Steger G, Greil R, Marth C, Kubista E, Samonigg H, Wohlmuth P, Mittlbock M, Jakesz R; Austrian Breast and Colorectal Cancer Study Group (ABCSG). Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy. Lancet Oncol. 2008 Sep;9(9):840-9. doi: 10.1016/S1470-2045(08)70204-3. Epub 2008 Aug 19.

  PMID: 18718815 BACKGROUND

• Gnant MF, Mlineritsch B, Luschin-Ebengreuth G, Grampp S, Kaessmann H, Schmid M, Menzel C, Piswanger-Soelkner JC, Galid A, Mittlboeck M, Hausmaninger H, Jakesz R; Austrian Breast and Colorectal Cancer Study Group. Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2007 Mar 1;25(7):820-8. doi: 10.1200/JCO.2005.02.7102. Epub 2006 Dec 11.

  PMID: 17159195 BACKGROUND

• Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Postlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, Samonigg H, Tausch C, Eidtmann H, Steger G, Kwasny W, Dubsky P, Fridrik M, Fitzal F, Stierer M, Rucklinger E, Greil R; ABCSG-12 Trial Investigators; Marth C. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 2009 Feb 12;360(7):679-91. doi: 10.1056/NEJMoa0806285.

  PMID: 19213681 BACKGROUND

• Gnant M, Dubsky P, Fitzal F, Blaha P, Schoppmann S, Steger G, Marth C, Samonigg H, Huttner K, Fohler H, Ruecklinger E, Jakesz R, Greil R; Austrian Breast and Colorectal Cancer Study Group. Maintaining bone density in patients undergoing treatment for breast cancer: is there an adjuvant benefit? Clin Breast Cancer. 2009 Jun;9 Suppl 1:S18-27. doi: 10.3816/CBC.2009.s.002.

  PMID: 19561003 BACKGROUND

• Gnant M. Can oral bisphosphonates really reduce the risk of breast cancer in healthy women? J Clin Oncol. 2010 Aug 1;28(22):3548-51. doi: 10.1200/JCO.2010.29.6327. Epub 2010 Jun 21. No abstract available.

  PMID: 20567005 BACKGROUND

• Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Heck D, Menzel C, Jakesz R, Seifert M, Hubalek M, Pristauz G, Bauernhofer T, Eidtmann H, Eiermann W, Steger G, Kwasny W, Dubsky P, Hochreiner G, Forsthuber EP, Fesl C, Greil R; Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol. 2011 Jul;12(7):631-41. doi: 10.1016/S1470-2045(11)70122-X. Epub 2011 Jun 5.

  PMID: 21641868 BACKGROUND

• Gnant M. Zoledronic acid in breast cancer: latest findings and interpretations. Ther Adv Med Oncol. 2011 Nov;3(6):293-301. doi: 10.1177/1758834011420599.

  PMID: 22084643 BACKGROUND

• Pfeiler G, Konigsberg R, Fesl C, Mlineritsch B, Stoeger H, Singer CF, Postlberger S, Steger GG, Seifert M, Dubsky P, Taucher S, Samonigg H, Bjelic-Radisic V, Greil R, Marth C, Gnant M. Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. J Clin Oncol. 2011 Jul 1;29(19):2653-9. doi: 10.1200/JCO.2010.33.2585. Epub 2011 May 9.

  PMID: 21555684 BACKGROUND

• Ressler S, Mlineritsch B, Greil R. Zoledronic acid for adjuvant use in patients with breast cancer. Expert Rev Anticancer Ther. 2011 Mar;11(3):333-49. doi: 10.1586/era.11.13.

  PMID: 21417849 BACKGROUND

• Hadji P, Coleman R, Gnant M, Green J. The impact of menopause on bone, zoledronic acid, and implications for breast cancer growth and metastasis. Ann Oncol. 2012 Nov;23(11):2782-2790. doi: 10.1093/annonc/mds169. Epub 2012 Jun 22.

  PMID: 22730099 BACKGROUND

• Rugani P, Luschin G, Jakse N, Kirnbauer B, Lang U, Acham S. Prevalence of bisphosphonate-associated osteonecrosis of the jaw after intravenous zoledronate infusions in patients with early breast cancer. Clin Oral Investig. 2014;18(2):401-7. doi: 10.1007/s00784-013-1012-5. Epub 2013 Jun 10.

  PMID: 23749244 BACKGROUND

• Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Knauer M, Moik M, Jakesz R, Seifert M, Taucher S, Bjelic-Radisic V, Balic M, Eidtmann H, Eiermann W, Steger G, Kwasny W, Dubsky P, Selim U, Fitzal F, Hochreiner G, Wette V, Sevelda P, Ploner F, Bartsch R, Fesl C, Greil R; Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12. Ann Oncol. 2015 Feb;26(2):313-20. doi: 10.1093/annonc/mdu544. Epub 2014 Nov 17.

  PMID: 25403582 BACKGROUND

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015 Oct 3;386(10001):1353-1361. doi: 10.1016/S0140-6736(15)60908-4. Epub 2015 Jul 23.

  PMID: 26211824 BACKGROUND

• Lipton A, Gnant M, Aapro M. Managing aromatase inhibitor-associated bone loss in breast cancer. Womens Health (Lond). 2007 Jul;3(4):441-8. doi: 10.2217/17455057.3.4.441.

  PMID: 19804020 BACKGROUND

• Adams A, Jakob T, Huth A, Monsef I, Ernst M, Kopp M, Caro-Valenzuela J, Wockel A, Skoetz N. Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2024 Jul 9;7(7):CD013451. doi: 10.1002/14651858.CD013451.pub2.

  PMID: 38979716 DERIVED

• Beltran-Bless AA, Clemons MJ, Fesl C, Greil R, Pond GR, Balic M, Vandermeer L, Bjelic-Radisic V, Singer CF, Steger GG, Helfgott R, Egle D, Solkner L, Gampenrieder SP, Kacerovsky-Strobl S, Suppan C, Ritter M, Rinnerthaler G, Pfeiler G, Fohler H, Hlauschek D, Hilton J, Gnant M. Does the number of 6-monthly adjuvant zoledronate infusions received affect treatment efficacy for early breast cancer? A sub-study of ABCSG-12. Eur J Cancer. 2023 Feb;180:108-116. doi: 10.1016/j.ejca.2022.12.003. Epub 2022 Dec 10.

  PMID: 36592505 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Tamoxifen; Anastrozole; Zoledronic Acid; Goserelin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Imidazoles; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Trial Office Director
• Organization: ABCSG (Austrian Breast & Colorectal Cancer Study Group)

info@abcsg.at

+43 1 4089230

Study Officials

• Raimund Jakesz, MD

  Austrian Breast & Colorectal Cancer Study Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2006
• First Posted: February 24, 2006
• Study Start: June 1, 1999
• Primary Completion: March 27, 2008
• Study Completion: June 26, 2018
• Last Updated: March 15, 2024
• Results First Posted: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (62); DE (10)