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| ID | Type | Description | Link |
|---|---|---|---|
| CZOL 446 1B 01 | Other Identifier | Novartis | |
| Zol-A-01 | Other Identifier | Novartis |
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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
| Novartis Pharmaceuticals | INDUSTRY |
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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AZ (Arimidex+Zoledronate) | Active Comparator | Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid) |
|
| TZ (Tamoxifen+Zoledronate) | Active Comparator | Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid) |
|
| AC (Arimidex Control) | Active Comparator | Study Drug Arimidex (Anastrozole) |
|
| TC (Tamoxifen Control) | Active Comparator | Study Drug Nolvadex (Tamoxifen) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tamoxifen | Drug | 20 mg/d |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Raimund Jakesz, MD | Austrian Breast & Colorectal Cancer Study Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital of Guessing | Guessing | Burgenland | 7540 | Austria | ||
| Hospital Oberpullendorf |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18718815 | Background | 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. | |
| 17159195 |
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The first patient was randomized June 17, 1999, the last patient was randomized May 17, 2006. Randomization took place in 66 Austrian and 10 German clinical sites. In total, 1.803 patients were enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | AZ (Arimidex+Zoledronate) | Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid) anastrozole: 1 mg/d zoledronic acid: 4 mg q6m goserelin: 3.6 mg goserelin subcutaneously every 28 days |
| FG001 | TZ (Tamoxifen+Zoledronate) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| anastrozole | Drug | 1 mg/d |
|
|
| zoledronic acid | Drug | 4 mg q6m |
|
|
| goserelin | Other | 3.6 mg goserelin subcutaneously every 28 days |
|
| 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 | 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 | 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 | 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. |
| Oberpullendorf |
| Burgenland |
| 7350 |
| Austria |
| Hospital Oberwart | Oberwart | Burgenland | 7400 | Austria |
| State Hospital Klagenfurt, Surgery | Klagenfurt | Carinthia | 9026 | Austria |
| State Hospital Klagenfurt | Klagenfurt | Carinthia | 9026 | Austria |
| Hospital BHB St. Veit | Saint Veit A. D. Glan | Carinthia | 9300 | Austria |
| Ordination Dr. Wette | Saint Veit A. D. Glan | Carinthia | 9300 | Austria |
| State Hospital Villach | Villach | Carinthia | 9500 | Austria |
| Privat Hospital Villach | Villach | Carinthia | 9504 | Austria |
| State Hospital Wolfsberg | Wolfsberg | Carinthia | 9400 | Austria |
| Hospital Hainburg | Hainburg an der Donau | Lower Austria | 2410 | Austria |
| Hospital Klosterneuburg, Internal Medicine | Klosterneuburg | Lower Austria | 3400 | Austria |
| Hospital Krems | Krems | Lower Austria | 3500 | Austria |
| Hospital Melk | Melk | Lower Austria | 3390 | Austria |
| Hospital Mistelbach | Mistelbach | Lower Austria | 2130 | Austria |
| Hospital Mödling | Mödling | Lower Austria | 2340 | Austria |
| Hospital Neunkirchen | Neunkirchen | Lower Austria | 2620 | Austria |
| Hospital St. Poelten | Sankt Pölten | Lower Austria | 3100 | Austria |
| Hospital Scheibbs | Scheibbs | Lower Austria | 3270 | Austria |
| Hospital Tulln | Tulln | Lower Austria | 3430 | Austria |
| Hospital Waidhofen/Thaya | Waidhofen an der Thaya | Lower Austria | 3830 | Austria |
| Hospital of Wiener Neustadt | Wiener Neustadt | Lower Austria | 2700 | Austria |
| Kardinal Schwarzenberg'sches Hospital | Schwarzach | State of Salzburg | 5620 | Austria |
| State Hospital Feldbach | Feldbach | Styria | 8330 | Austria |
| 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 Rottenmann | Rottenmann | Styria | 8786 | Austria |
| Brustgesundheitszentrum-Süd Institut / Dr. Thiel | Weiz | Styria | 8160 | Austria |
| District Hospital Hall in Tirol | Hall in Tirol | Tyrol | 6060 | Austria |
| Gynaegological Medical University Innsbruck | Innsbruck | Tyrol | 6020 | Austria |
| District Hospital Kufstein | Kufstein | Tyrol | 6330 | Austria |
| District Hospital Lienz | Lienz | Tyrol | 9900 | Austria |
| Hospital St. Vinzenz | Zams | Tyrol | 6511 | 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 BHS Linz | Linz | Upper Austria | 4010 | Austria |
| Hospital Elisabethinen Linz | Linz | Upper Austria | 4010 | Austria |
| General Hospital Linz | Linz | Upper Austria | 4020 | Austria |
| Hospital BHB Linz | Linz | Upper Austria | 4020 | Austria |
| Ordination Dr. Pöstlberger | Linz | Upper Austria | 4020 | Austria |
| Hospital BHS Ried | Ried | Upper Austria | 4910 | Austria |
| State Hospital Rohrbach | Rohrbach | Upper Austria | 4150 | Austria |
| State Hospital Schärding | Schaerding | Upper Austria | 4780 | Austria |
| State Hospital Steyr | Steyr | Upper Austria | 4400 | Austria |
| State Hospital Voecklabruck, Internal Medicine | Vöcklabruck | Upper Austria | 4840 | Austria |
| State Hospital Voecklabruck, Surgery Dept. | Vöcklabruck | Upper Austria | 4840 | Austria |
| Klinikum Wels-Grieskirchen | Wels | Upper Austria | 4600 | Austria |
| State Hospital Bregenz | Bregenz | Vorarlberg | 6900 | Austria |
| State Hospital of Dornbirn | Dornbirn | Vorarlberg | 6850 | Austria |
| State Hospital Feldkirch | Feldkirch | Vorarlberg | 6807 | Austria |
| Paracelsus Medical University Salzburg - Oncology | Salzburg | 5020 | Austria |
| Hospital BHB Vienna, Surgery | Vienna | 1020 | Austria |
| Hospital Sanatorium Hera | Vienna | 1090 | Austria |
| Medical University of Vienna, General Hospital, Gynaecology and Obstetrics | Vienna | 1090 | Austria |
| Medical University of Vienna, General Hospital | Vienna | 1090 | Austria |
| Medical University Vienna, General Hospital | Vienna | 1090 | Austria |
| State Hospital Vienna-Hietzing | Vienna | 1130 | Austria |
| Hanusch Hospital | Vienna | 1140 | Austria |
| Wilheminenspital, Internal Medicin I | Vienna | 1160 | Austria |
| Practice Dr. Marschner | Freiburg im Breisgau | Baden-Wurttemberg | 79106 | Germany |
| Medical Care Center | Ulm | Baden-Wurttemberg | 89073 | Germany |
| Klinikum St. Marien | Amberg | Bavaria | 92224 | Germany |
| Med. University of Munich | Munich | Bavaria | 80337 | Germany |
| Frauenklinik vom Roten Kreuz | Munich | Bavaria | 80637 | Germany |
| Elisabeth-Hospital | Kassel | Hesse | 34117 | Germany |
| Internal-haematological Practice Oldenburg | Oldenburg | Lower Saxony | 26121 | Germany |
| General Hospital Gifhorn | Gifhorn | Saxony | 38518 | Germany |
| Medical University Kiel | Kiel | Schleswig-Holstein | 24105 | Germany |
| Vivantes-Klinikum Friedrichshain | Berlin | 10967 | Germany |
| 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. |
| 19213681 | 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. |
| 19561003 | 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. |
| 20567005 | 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. |
| 21641868 | 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. |
| 22084643 | 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. |
| 21555684 | 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. |
| 21417849 | 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. |
| 22730099 | 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. |
| 23749244 | 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. |
| 25403582 | 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. |
| 26211824 | 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. |
| 19804020 | 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. |
| 38979716 | Derived | 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. |
| 36592505 | 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. |
Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid) tamoxifen: 20 mg/d zoledronic acid: 4 mg q6m goserelin: 3.6 mg goserelin subcutaneously every 28 days |
| FG002 | AC (Arimidex Control) | Study Drug Arimidex (Anastrozole) anastrozole: 1 mg/d goserelin: 3.6 mg goserelin subcutaneously every 28 days |
| FG003 | TC (Tamoxifen Control) | Study Drug Nolvadex (Tamoxifen) tamoxifen: 20 mg/d goserelin: 3.6 mg goserelin subcutaneously every 28 days |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | AZ (Arimidex+Zoledronate) | Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid) anastrozole: 1 mg/d zoledronic acid: 4 mg q6m goserelin: 3.6 mg goserelin subcutaneously every 28 days |
| BG001 | TZ (Tamoxifen+Zoledronate) | Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid) tamoxifen: 20 mg/d zoledronic acid: 4 mg q6m goserelin: 3.6 mg goserelin subcutaneously every 28 days |
| BG002 | AC (Arimidex Control) | Study Drug Arimidex (Anastrozole) anastrozole: 1 mg/d goserelin: 3.6 mg goserelin subcutaneously every 28 days |
| BG003 | TC (Tamoxifen Control) | Study Drug Nolvadex (Tamoxifen) tamoxifen: 20 mg/d goserelin: 3.6 mg goserelin subcutaneously every 28 days |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| pT-stage | The pathologic T-stage (pT) describes the categories of tumor size: pT1: <2 cm, pT2: 2 to 5 cm, pT3: > 5 cm. | Count of Participants | Participants |
| |||||||||||||||
| pN-stage | The pathologic N-stage (pN) describes the categories of affected lymph nodes: negative: no lymph node affected, positive: at least one lymph node affected. | Count of Participants | Participants |
| |||||||||||||||
| Histologic grade | The histologic grade describes to which extent the cancer cells and their arrangement look look like normal cells. Grade 1 (G1): well-differentiated, cells look more like normal breast tissue; Grade (G2): moderately differentiated; Grade (G3): poorly differentiated; GX: grade cannot be assessed. | Count of Participants | Participants |
| |||||||||||||||
| Estrogen receptor status | Count of Participants | Participants |
| ||||||||||||||||
| Progesterone receptor status | Count of Participants | Participants |
| ||||||||||||||||
| Preoperative chemotherapy | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Intent-to-treat population: All participants assigned to one of the four treatment arms were included in the analysis | Posted | Median | Inter-Quartile Range | years | 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. |
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| Primary | 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 | Intent-to-treat population: All participants assigned to one of the four treatment arms were included in the analysis | Posted | Median | Inter-Quartile Range | years | 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. |
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| Secondary | 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 | Intent-to-treat population: All participants assigned to one of the four treatment arms were included in the analysis | Posted | Median | Inter-Quartile Range | years | 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. |
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| Secondary | 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 | Intent-to-treat population: All participants assigned to one of the four treatment arms were included in the analysis | Posted | Median | Inter-Quartile Range | years | 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. |
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| Secondary | 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 | Intent-to-treat population: All participants assigned to one of the four treatment arms were included in the analysis | Posted | Median | Inter-Quartile Range | years | 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 | 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 | Intent-to-treat population: All participants assigned to one of the four treatment arms were included in the analysis. | Posted | Median | Inter-Quartile Range | years | 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. |
|
Maximum observation period per patient for all-cause mortality was 102 months starting with randomization. Reporting period for adverse events started with randomization and lasted until the first follow-up visit after the last treatment.
All-cause mortality data presented for intention-to-treat analysis set and for the entire study. Serious adverse events (SAEs) reported during treatment phase plus 30 days, and after this period only if the investigator could not preclude a causal link to treatment with Anastrozole. Other adverse events were collected from randomization until the first follow-up visit after the last treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AZ (Arimidex+Zoledronate) | Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid) anastrozole: 1 mg/d zoledronic acid: 4 mg q6m goserelin: 3.6 mg goserelin subcutaneously every 28 days | 9 | 450 | 67 | 450 | 355 | 450 |
| EG001 | TZ (Tamoxifen+Zoledronate) | Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid) tamoxifen: 20 mg/d zoledronic acid: 4 mg q6m goserelin: 3.6 mg goserelin subcutaneously every 28 days | 7 | 450 | 103 | 450 | 320 | 450 |
| EG002 | AC (Arimidex Control) | Study Drug Arimidex (Anastrozole) anastrozole: 1 mg/d goserelin: 3.6 mg goserelin subcutaneously every 28 days | 18 | 453 | 55 | 453 | 340 | 453 |
| EG003 | TC (Tamoxifen Control) | Study Drug Nolvadex (Tamoxifen) tamoxifen: 20 mg/d goserelin: 3.6 mg goserelin subcutaneously every 28 days | 8 | 450 | 93 | 450 | 290 | 450 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Breast inflammation | Reproductive system and breast disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Cutaneous reaction | Skin and subcutaneous tissue disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Disease of liver / gallbladder | Hepatobiliary disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Fever | General disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Fracture | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Hemorrhoids | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Hypertonia | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Incontinence | Renal and urinary disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Insult / TIA | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Irregular vaginal discharge | Reproductive system and breast disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Lung inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Lymphedema (arm, hand) | Vascular disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.1 | Systematic Assessment |
| |
| Obstipation | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Other tumors | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.1 | Systematic Assessment |
| |
| Ovarian changes | Reproductive system and breast disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Periodontal disease | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Peripheral nerve disease | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Psychological disorder NOS | Psychiatric disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Sensory disturbance | Nervous system disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Skin disease | Skin and subcutaneous tissue disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Spinal troubles/pain | Musculoskeletal and connective tissue disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Stomach pain | Gastrointestinal disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Thyroid disease | Endocrine disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Tinnitus/hearing loss | Ear and labyrinth disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Torn ligament/Meniscus lesion | Injury, poisoning and procedural complications | MedDRA 10.1 | Systematic Assessment |
| |
| Uro-genital tract infection | Infections and infestations | MedDRA 10.1 | Systematic Assessment |
| |
| Uterine polyp | Reproductive system and breast disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Vaginal bleeding | Reproductive system and breast disorders | MedDRA 10.1 | Systematic Assessment |
| |
| Vaginal inflammation | Reproductive system and breast disorders | MedDRA 10.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Breast inflammation | Reproductive system and breast disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Cutaneous reaction | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Fever | General disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Fracture | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
| |
| Hair loss | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Hemorrhoids | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Hot flushes | Vascular disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Hypercalcemia | Metabolism and nutrition disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Hypertonia | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Impaired vision | Eye disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Incontinence | Renal and urinary disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Infection of ear, nose, or throat | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
| |
| Irregular vaginal discharge | Reproductive system and breast disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Leg edema | General disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Lung inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Lymphedema (arm, hand) | Vascular disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Morning stiffness | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Muscle cramp | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Nausea and vomiting | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Obstipation | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Other/minor (not categorized) | General disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Ovarian changes | Reproductive system and breast disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Periodontal disease* | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Peripheral nerve disease | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Psychological disorder NOS | Psychiatric disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Sensory disturbance | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Skin disease | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Spinal troubles/pain | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Stomach pain | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Thyroid disease | Endocrine disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Tinnitus/hearing loss | Ear and labyrinth disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Torn ligament/Meniscus lesion | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
| |
| Uro-genital tract infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
| |
| Uterine polyp | Reproductive system and breast disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Vaginal bleeding | Reproductive system and breast disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Vaginal discharge | Reproductive system and breast disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Vaginal dryness | Reproductive system and breast disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Vaginal inflammation | Reproductive system and breast disorders | MedDRA (10.1) | Systematic Assessment |
| |
| Weight gain | Investigations | MedDRA (10.1) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Office Director | ABCSG (Austrian Breast & Colorectal Cancer Study Group) | +43 1 4089230 | info@abcsg.at |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D013629 | Tamoxifen |
| D000077384 | Anastrozole |
| D000077211 | Zoledronic Acid |
| D017273 | Goserelin |
| ID | Term |
|---|---|
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D009570 | Nitriles |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D007093 | Imidazoles |
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
Not provided
Not provided
| Male |
|
| pT2/pT3 |
|
| Unknown |
|
| Positive |
|
| Unknown |
|
| G3 |
|
| GX |
|
| Unknown |
|
| Positive |
|
| Unknown |
|
| Positive |
|
| Unknown |
|
| Yes |
|
| Unknown |
|
| Superiority |
A two-sided significance level of 2.5% was used in this 2x2 factorial design of two primary endpoints according to the Bonferroni-Holm adjustment to control multiplicity. |
| OG003 | TC (Tamoxifen Control) | Study Drug Nolvadex (Tamoxifen) tamoxifen: 20 mg/d goserelin: 3.6 mg goserelin subcutaneously every 28 days |
|
|
|
| OG003 | TC (Tamoxifen Control) | Study Drug Nolvadex (Tamoxifen) tamoxifen: 20 mg/d goserelin: 3.6 mg goserelin subcutaneously every 28 days |
|
|
|
| OG003 | TC (Tamoxifen Control) | Study Drug Nolvadex (Tamoxifen) tamoxifen: 20 mg/d goserelin: 3.6 mg goserelin subcutaneously every 28 days |
|
|
|
| OG003 |
| TC (Tamoxifen Control) |
Study Drug Nolvadex (Tamoxifen) tamoxifen: 20 mg/d goserelin: 3.6 mg goserelin subcutaneously every 28 days |
|
|
|
| OG003 | TC (Tamoxifen Control) | Study Drug Nolvadex (Tamoxifen) tamoxifen: 20 mg/d goserelin: 3.6 mg goserelin subcutaneously every 28 days |
|
|
|