Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid

NCT ID: NCT00295646

Last Updated: 2024-03-15

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1803 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-06-30

Study Completion Date

2018-06-26

Brief Summary

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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

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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).

Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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AZ (Arimidex+Zoledronate)

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

Group Type ACTIVE_COMPARATOR

anastrozole

Intervention Type DRUG

1 mg/d

zoledronic acid

Intervention Type DRUG

4 mg q6m

goserelin

Intervention Type OTHER

3.6 mg goserelin subcutaneously every 28 days

TZ (Tamoxifen+Zoledronate)

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

Group Type ACTIVE_COMPARATOR

tamoxifen

Intervention Type DRUG

20 mg/d

zoledronic acid

Intervention Type DRUG

4 mg q6m

goserelin

Intervention Type OTHER

3.6 mg goserelin subcutaneously every 28 days

AC (Arimidex Control)

Study Drug Arimidex (Anastrozole)

Group Type ACTIVE_COMPARATOR

anastrozole

Intervention Type DRUG

1 mg/d

goserelin

Intervention Type OTHER

3.6 mg goserelin subcutaneously every 28 days

TC (Tamoxifen Control)

Study Drug Nolvadex (Tamoxifen)

Group Type ACTIVE_COMPARATOR

tamoxifen

Intervention Type DRUG

20 mg/d

goserelin

Intervention Type OTHER

3.6 mg goserelin subcutaneously every 28 days

Interventions

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tamoxifen

20 mg/d

Intervention Type DRUG

anastrozole

1 mg/d

Intervention Type DRUG

zoledronic acid

4 mg q6m

Intervention Type DRUG

goserelin

3.6 mg goserelin subcutaneously every 28 days

Intervention Type OTHER

Other Intervention Names

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Nolvadex Arimidex Zoledronate, Zometa

Eligibility Criteria

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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
Minimum Eligible Age

19 Years

Maximum Eligible Age

59 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Austrian Breast & Colorectal Cancer Study Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Raimund Jakesz, MD

Role: PRINCIPAL_INVESTIGATOR

Austrian Breast & Colorectal Cancer Study Group

Locations

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Hospital of Guessing

Güssing, Burgenland, Austria

Site Status

Hospital Oberpullendorf

Oberpullendorf, Burgenland, Austria

Site Status

Hospital Oberwart

Oberwart, Burgenland, Austria

Site Status

State Hospital Klagenfurt, Surgery

Klagenfurt, Carinthia, Austria

Site Status

State Hospital Klagenfurt

Klagenfurt, Carinthia, Austria

Site Status

Hospital BHB St. Veit

Saint Veit A. D. Glan, Carinthia, Austria

Site Status

Ordination Dr. Wette

Saint Veit A. D. Glan, Carinthia, Austria

Site Status

State Hospital Villach

Villach, Carinthia, Austria

Site Status

Privat Hospital Villach

Villach, Carinthia, Austria

Site Status

State Hospital Wolfsberg

Wolfsberg, Carinthia, Austria

Site Status

Hospital Hainburg

Hainburg an der Donau, Lower Austria, Austria

Site Status

Hospital Klosterneuburg, Internal Medicine

Klosterneuburg, Lower Austria, Austria

Site Status

Hospital Krems

Krems, Lower Austria, Austria

Site Status

Hospital Melk

Melk, Lower Austria, Austria

Site Status

Hospital Mistelbach

Mistelbach, Lower Austria, Austria

Site Status

Hospital Mödling

Mödling, Lower Austria, Austria

Site Status

Hospital Neunkirchen

Neunkirchen, Lower Austria, Austria

Site Status

Hospital St. Poelten

Sankt Pölten, Lower Austria, Austria

Site Status

Hospital Scheibbs

Scheibbs, Lower Austria, Austria

Site Status

Hospital Tulln

Tulln, Lower Austria, Austria

Site Status

Hospital Waidhofen/Thaya

Waidhofen an der Thaya, Lower Austria, Austria

Site Status

Hospital of Wiener Neustadt

Wiener Neustadt, Lower Austria, Austria

Site Status

Kardinal Schwarzenberg'sches Hospital

Schwarzach, Salzburg, Austria

Site Status

State Hospital Feldbach

Feldbach, Styria, Austria

Site Status

Gynaegological Medical University of Graz

Graz, Styria, Austria

Site Status

Medical University of Graz, Oncology

Graz, Styria, Austria

Site Status

State Hospital Leoben

Leoben, Styria, Austria

Site Status

State Hospital Rottenmann

Rottenmann, Styria, Austria

Site Status

Brustgesundheitszentrum-Süd Institut / Dr. Thiel

Weiz, Styria, Austria

Site Status

District Hospital Hall in Tirol

Hall in Tirol, Tyrol, Austria

Site Status

Gynaegological Medical University Innsbruck

Innsbruck, Tyrol, Austria

Site Status

District Hospital Kufstein

Kufstein, Tyrol, Austria

Site Status

District Hospital Lienz

Lienz, Tyrol, Austria

Site Status

Hospital St. Vinzenz

Zams, Tyrol, Austria

Site Status

State Hospital Bad Ischl

Bad Ischl, Upper Austria, Austria

Site Status

State Hospital Freistadt

Freistadt, Upper Austria, Austria

Site Status

State Hospital Gmunden

Gmunden, Upper Austria, Austria

Site Status

State Hospital Kirchdorf

Kirchdorf, Upper Austria, Austria

Site Status

Hospital BHS Linz

Linz, Upper Austria, Austria

Site Status

Hospital Elisabethinen Linz

Linz, Upper Austria, Austria

Site Status

General Hospital Linz

Linz, Upper Austria, Austria

Site Status

Hospital BHB Linz

Linz, Upper Austria, Austria

Site Status

Ordination Dr. Pöstlberger

Linz, Upper Austria, Austria

Site Status

Hospital BHS Ried

Ried, Upper Austria, Austria

Site Status

State Hospital Rohrbach

Rohrbach, Upper Austria, Austria

Site Status

State Hospital Schärding

Schärding, Upper Austria, Austria

Site Status

State Hospital Steyr

Steyr, Upper Austria, Austria

Site Status

State Hospital Voecklabruck, Internal Medicine

Vöcklabruck, Upper Austria, Austria

Site Status

State Hospital Voecklabruck, Surgery Dept.

Vöcklabruck, Upper Austria, Austria

Site Status

Klinikum Wels-Grieskirchen

Wels, Upper Austria, Austria

Site Status

State Hospital Bregenz

Bregenz, Vorarlberg, Austria

Site Status

State Hospital of Dornbirn

Dornbirn, Vorarlberg, Austria

Site Status

State Hospital Feldkirch

Feldkirch, Vorarlberg, Austria

Site Status

Paracelsus Medical University Salzburg - Oncology

Salzburg, , Austria

Site Status

Hospital BHB Vienna, Surgery

Vienna, , Austria

Site Status

Hospital Sanatorium Hera

Vienna, , Austria

Site Status

Medical University of Vienna, General Hospital, Gynaecology and Obstetrics

Vienna, , Austria

Site Status

Medical University of Vienna, General Hospital

Vienna, , Austria

Site Status

Medical University Vienna, General Hospital

Vienna, , Austria

Site Status

State Hospital Vienna-Hietzing

Vienna, , Austria

Site Status

Hanusch Hospital

Vienna, , Austria

Site Status

Wilheminenspital, Internal Medicin I

Vienna, , Austria

Site Status

Practice Dr. Marschner

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Site Status

Medical Care Center

Ulm, Baden-Wurttemberg, Germany

Site Status

Klinikum St. Marien

Amberg, Bavaria, Germany

Site Status

Med. University of Munich

Munich, Bavaria, Germany

Site Status

Frauenklinik vom Roten Kreuz

Munich, Bavaria, Germany

Site Status

Elisabeth-Hospital

Kassel, Hesse, Germany

Site Status

Internal-haematological Practice Oldenburg

Oldenburg, Lower Saxony, Germany

Site Status

General Hospital Gifhorn

Gifhorn, Saxony, Germany

Site Status

Medical University Kiel

Kiel, Schleswig-Holstein, Germany

Site Status

Vivantes-Klinikum Friedrichshain

Berlin, , Germany

Site Status

Countries

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Austria Germany

References

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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.

Reference Type BACKGROUND
PMID: 18718815 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17159195 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19213681 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19561003 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20567005 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21641868 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22084643 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21555684 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21417849 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22730099 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23749244 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25403582 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26211824 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19804020 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38979716 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36592505 (View on PubMed)

Other Identifiers

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CZOL 446 1B 01

Identifier Type: OTHER

Identifier Source: secondary_id

Zol-A-01

Identifier Type: OTHER

Identifier Source: secondary_id

ABCSG-12

Identifier Type: -

Identifier Source: org_study_id

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