Breast CancerPhase 3NCT00295646
Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid
A Phase 3 study testing tamoxifen, anastrozole and zoledronic acid in people with Breast Cancer, run by Austrian Breast & Colorectal Cancer Study Group at 72 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 59 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- tamoxifen, anastrozole and zoledronic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,803 participants
- Where
- 72 sitesin 2 countries
- Study dates
- Jun 1999to 26 Jun 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 59 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
72 sites in 2 countries.
72 sites in 2 countries
Austria62 sites
State Hospital Bad Ischl
Bad Ischl, Upper Austria, 4820
State Hospital Bregenz
Bregenz, Vorarlberg, 6900
State Hospital of Dornbirn
Dornbirn, Vorarlberg, 6850
State Hospital Feldbach
Feldbach, Styria, 8330
State Hospital Feldkirch
Feldkirch, Vorarlberg, 6807
State Hospital Freistadt
Freistadt, Upper Austria, 4240
State Hospital Gmunden
Gmunden, Upper Austria, 4810
Gynaegological Medical University of Graz
Graz, Styria, 8036
Medical University of Graz, Oncology
Graz, Styria, 8036
Hospital of Guessing
Guessing, Burgenland, 7540
Hospital Hainburg
Hainburg an der Donau, Lower Austria, 2410
District Hospital Hall in Tirol
Hall in Tirol, Tyrol, 6060
Gynaegological Medical University Innsbruck
Innsbruck, Tyrol, 6020
State Hospital Kirchdorf
Kirchdorf, Upper Austria, 4560
State Hospital Klagenfurt, Surgery
Klagenfurt, Carinthia, 9026
State Hospital Klagenfurt
Klagenfurt, Carinthia, 9026
Hospital Klosterneuburg, Internal Medicine
Klosterneuburg, Lower Austria, 3400
Hospital Krems
Krems, Lower Austria, 3500
District Hospital Kufstein
Kufstein, Tyrol, 6330
State Hospital Leoben
Leoben, Styria, 8700
District Hospital Lienz
Lienz, Tyrol, 9900
Hospital BHS Linz
Linz, Upper Austria, 4010
Hospital Elisabethinen Linz
Linz, Upper Austria, 4010
General Hospital Linz
Linz, Upper Austria, 4020
Hospital BHB Linz
Linz, Upper Austria, 4020
Ordination Dr. Pöstlberger
Linz, Upper Austria, 4020
Hospital Melk
Melk, Lower Austria, 3390
Hospital Mistelbach
Mistelbach, Lower Austria, 2130
Hospital Mödling
Mödling, Lower Austria, 2340
Hospital Neunkirchen
Neunkirchen, Lower Austria, 2620
Hospital Oberpullendorf
Oberpullendorf, Burgenland, 7350
Hospital Oberwart
Oberwart, Burgenland, 7400
Hospital BHS Ried
Ried, Upper Austria, 4910
State Hospital Rohrbach
Rohrbach, Upper Austria, 4150
State Hospital Rottenmann
Rottenmann, Styria, 8786
Hospital BHB St. Veit
Saint Veit A. D. Glan, Carinthia, 9300
Ordination Dr. Wette
Saint Veit A. D. Glan, Carinthia, 9300
Paracelsus Medical University Salzburg - Oncology
Salzburg, 5020
Hospital St. Poelten
Sankt Pölten, Lower Austria, 3100
State Hospital Schärding
Schaerding, Upper Austria, 4780
Hospital Scheibbs
Scheibbs, Lower Austria, 3270
Kardinal Schwarzenberg'sches Hospital
Schwarzach, State of Salzburg, 5620
State Hospital Steyr
Steyr, Upper Austria, 4400
Hospital Tulln
Tulln, Lower Austria, 3430
Hospital BHB Vienna, Surgery
Vienna, 1020
Hospital Sanatorium Hera
Vienna, 1090
Medical University of Vienna, General Hospital, Gynaecology and Obstetrics
Vienna, 1090
Medical University of Vienna, General Hospital
Vienna, 1090
Medical University Vienna, General Hospital
Vienna, 1090
State Hospital Vienna-Hietzing
Vienna, 1130
Hanusch Hospital
Vienna, 1140
Wilheminenspital, Internal Medicin I
Vienna, 1160
State Hospital Villach
Villach, Carinthia, 9500
Privat Hospital Villach
Villach, Carinthia, 9504
State Hospital Voecklabruck, Internal Medicine
Vöcklabruck, Upper Austria, 4840
State Hospital Voecklabruck, Surgery Dept.
Vöcklabruck, Upper Austria, 4840
Hospital Waidhofen/Thaya
Waidhofen an der Thaya, Lower Austria, 3830
Brustgesundheitszentrum-Süd Institut / Dr. Thiel
Weiz, Styria, 8160
Klinikum Wels-Grieskirchen
Wels, Upper Austria, 4600
Hospital of Wiener Neustadt
Wiener Neustadt, Lower Austria, 2700
State Hospital Wolfsberg
Wolfsberg, Carinthia, 9400
Hospital St. Vinzenz
Zams, Tyrol, 6511
Germany10 sites
Klinikum St. Marien
Amberg, Bavaria, 92224
Vivantes-Klinikum Friedrichshain
Berlin, 10967
Practice Dr. Marschner
Freiburg im Breisgau, Baden-Wurttemberg, 79106
General Hospital Gifhorn
Gifhorn, Saxony, 38518
Elisabeth-Hospital
Kassel, Hesse, 34117
Medical University Kiel
Kiel, Schleswig-Holstein, 24105
Med. University of Munich
Munich, Bavaria, 80337
Frauenklinik vom Roten Kreuz
Munich, Bavaria, 80637
Internal-haematological Practice Oldenburg
Oldenburg, Lower Saxony, 26121
Medical Care Center
Ulm, Baden-Wurttemberg, 89073
About this study
Official title: 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.
Read the 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).
- Conditions
- Breast Cancer
- Being tested
- tamoxifen, anastrozole, zoledronic acid, goserelin
- 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
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tamoxifenDrug
Also called Nolvadex
20 mg/d
anastrozoleDrug
Also called Arimidex
1 mg/d
zoledronic acidDrug
Also called Zoledronate, Zometa
4 mg q6m
goserelinOther
3.6 mg goserelin subcutaneously every 28 days
| Study group | Role | What they receive |
|---|---|---|
| AZ (Arimidex+Zoledronate) | Active comparator | Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid) Receives: Drug: anastrozole; Drug: zoledronic acid; Other: goserelin |
| TZ (Tamoxifen+Zoledronate) | Active comparator | Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid) Receives: Drug: tamoxifen; Drug: zoledronic acid; Other: goserelin |
| AC (Arimidex Control) | Active comparator | Study Drug Arimidex (Anastrozole) Receives: Drug: anastrozole; Other: goserelin |
| TC (Tamoxifen Control) | Active comparator | Study Drug Nolvadex (Tamoxifen) Receives: Drug: tamoxifen; Other: goserelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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)
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
Measured: 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)
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
Measured: 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)
OS is defined as time from randomization to death from any cause
Measured: 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)
OS is defined as time from randomization to death from any cause
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2006 (estimated)
- Study startJun 1999
- Primary completion27 Mar 2008
- Study completion26 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,803 participants (actual)
Sponsor and investigators
- Lead sponsor
- Austrian Breast & Colorectal Cancer Study Group
- Sponsor type
- Research network
- Collaborators
- AstraZeneca, Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Raimund Jakesz, MD, Principal investigator, Austrian Breast & Colorectal Cancer Study Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00295646
- Sponsor's protocol ID
- ABCSG-12
- Other IDs
- CZOL 446 1B 01, Zol-A-01
- Status last verified
- Mar 2024
- First submitted
- 23 Feb 2006
- Last updated
- 15 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 18718815Gnant 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.
PubMed 17159195Gnant 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.
PubMed 19213681Gnant 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.
PubMed 19561003Gnant 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.
PubMed 20567005Gnant 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.
PubMed 21641868Gnant M. Zoledronic acid in breast cancer: latest findings and interpretations. Ther Adv Med Oncol. 2011 Nov;3(6):293-301. doi: 10.1177/1758834011420599.
PubMed 22084643Pfeiler 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.
PubMed 21555684Ressler 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.
PubMed 21417849Hadji 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.
PubMed 22730099Rugani 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.
PubMed 23749244Gnant 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.
PubMed 25403582Early 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.
PubMed 26211824Lipton 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.
PubMed 19804020Adams 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.
PubMed 38979716
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid, in Premenopausal, Hormone Receptor-positive Breast Cancer Patients (Stage I, II)
- ClinicalTrials.gov ID
- NCT00295646
- Acronym / sponsor ID
- ABCSG-12
- Conditions
- Breast Cancer
- Keywords
- Austrian Breast & Colorectal Cancer Study Group (ABCSG), 12, Phase 3, breast cancer, anastrozole, tamoxifen, zoledronic acid, premenopausal
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,803 participants (actual)
- Lead sponsor
- Austrian Breast & Colorectal Cancer Study GroupResearch network
- Collaborators
- AstraZeneca, Novartis Pharmaceuticals
- Study start
- Jun 1999
- Primary completion
- 27 Mar 2008 (actual)
- Study completion
- 26 Jun 2018 (actual)
- First posted
- 24 Feb 2006 (estimated)
- Results
- Posted 15 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| AZ (Arimidex+Zoledronate) | Active comparator | Drug: anastrozole, Drug: zoledronic acid, Other: goserelinStudy Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid) |
| TZ (Tamoxifen+Zoledronate) | Active comparator | Drug: tamoxifen, Drug: zoledronic acid, Other: goserelinStudy Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid) |
| AC (Arimidex Control) | Active comparator | Drug: anastrozole, Other: goserelinStudy Drug Arimidex (Anastrozole) |
| TC (Tamoxifen Control) | Active comparator | Drug: tamoxifen, Other: goserelinStudy Drug Nolvadex (Tamoxifen) |
Who may qualify
- Ages
- 19 to 59 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tamoxifenAlso: Nolvadex20 mg/d | Drug | TC (Tamoxifen Control), TZ (Tamoxifen+Zoledronate) |
| anastrozoleAlso: Arimidex1 mg/d | Drug | AC (Arimidex Control), AZ (Arimidex+Zoledronate) |
| zoledronic acidAlso: Zoledronate, Zometa4 mg q6m | Drug | AZ (Arimidex+Zoledronate), TZ (Tamoxifen+Zoledronate) |
| goserelin3.6 mg goserelin subcutaneously every 28 days | Other | AC (Arimidex Control), AZ (Arimidex+Zoledronate), TC (Tamoxifen Control), TZ (Tamoxifen+Zoledronate) |
Primary outcome
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
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
4 secondary outcomes
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18718815Gnant 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.
- Background: PubMed 17159195Gnant 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.
- Background: PubMed 19213681Gnant 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.
- Background: PubMed 19561003Gnant 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.
- Background: PubMed 20567005Gnant 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.
- Background: PubMed 21641868Gnant 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.
- Background: PubMed 22084643Gnant M. Zoledronic acid in breast cancer: latest findings and interpretations. Ther Adv Med Oncol. 2011 Nov;3(6):293-301. doi: 10.1177/1758834011420599.
- Background: PubMed 21555684Pfeiler 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.
- Background: PubMed 21417849Ressler 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.
- Background: PubMed 22730099Hadji 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.
- Background: PubMed 23749244Rugani 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.
- Background: PubMed 25403582Gnant 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raimund Jakesz, MD principal investigator
Austrian Breast & Colorectal Cancer Study Group
72 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing tamoxifen, anastrozole and zoledronic acid in people with Breast Cancer, run by Austrian Breast & Colorectal Cancer Study Group at 72 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 72 sites in Austria, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00295646, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2024.