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NCT00295646 · CITED IN SOURCE DOCUMENTS

Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2024-03-15

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Comparison of Zoledronate vs no Zoledronate in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Disease-free Survival (DFS)

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outcome · POSTED

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

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outcome · POSTED

Comparison of Zoledronate vs no Zoledronate in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Recurrence-free Survival (RFS)

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outcome · POSTED

Comparison of Anastrozole vs Tamoxifen in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Overall Survival (OS)

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outcome · POSTED

Comparison of Zoledronate vs no Zoledronate in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Overall Survival (OS)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * Premenopausal, hormone receptor-positive patient * Histologically verified (minimally) invasive breast cancer, local radical treatment * 0-9 involved axillary lymph nodes (≥ 10 histologically examined nodes) * Tumor stage: pT1b-3, yT0 or yT1a Exclusion Criteria: * T1a, T4d, yT4; M1 * Previous breast tumor irradiation * Previous or concurrent chemotherapy (except for preoperative chemotherapy) * Serum creatinine \> 1.5 x UNL or creatinine clearance \< 60 ml/min
healthy Volunteers
false
maximum Age
59 Years
minimum Age
19 Years
sex
FEMALE
std Ages
  1. ADULT
Treatment arms and interventions
arm Groups
  1. description
    Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid)
    intervention Names
    1. Drug: anastrozole
    2. Drug: zoledronic acid
    3. Other: goserelin
    label
    AZ (Arimidex+Zoledronate)
    type
    ACTIVE_COMPARATOR
  2. description
    Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid)
    intervention Names
    1. Drug: tamoxifen
    2. Drug: zoledronic acid
    3. Other: goserelin
    label
    TZ (Tamoxifen+Zoledronate)
    type
    ACTIVE_COMPARATOR
  3. description
    Study Drug Arimidex (Anastrozole)
    intervention Names
    1. Drug: anastrozole
    2. Other: goserelin
    label
    AC (Arimidex Control)
    type
    ACTIVE_COMPARATOR
  4. description
    Study Drug Nolvadex (Tamoxifen)
    intervention Names
    1. Drug: tamoxifen
    2. Other: goserelin
    label
    TC (Tamoxifen Control)
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. TC (Tamoxifen Control)
    2. TZ (Tamoxifen+Zoledronate)
    description
    20 mg/d
    name
    tamoxifen
    other Names
    1. Nolvadex
    type
    DRUG
  2. arm Group Labels
    1. AC (Arimidex Control)
    2. AZ (Arimidex+Zoledronate)
    description
    1 mg/d
    name
    anastrozole
    other Names
    1. Arimidex
    type
    DRUG
  3. arm Group Labels
    1. AZ (Arimidex+Zoledronate)
    2. TZ (Tamoxifen+Zoledronate)
    description
    4 mg q6m
    name
    zoledronic acid
    other Names
    1. Zoledronate, Zometa
    type
    DRUG
  4. arm Group Labels
    1. AC (Arimidex Control)
    2. AZ (Arimidex+Zoledronate)
    3. TC (Tamoxifen Control)
    4. TZ (Tamoxifen+Zoledronate)
    description
    3.6 mg goserelin subcutaneously every 28 days
    name
    goserelin
    type
    OTHER
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
1803
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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
    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.
  2. description
    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
    measure
    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.
secondary Outcomes
  1. description
    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
    measure
    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.
  2. description
    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
    measure
    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.
  3. description
    OS is defined as time from randomization to death from any cause
    measure
    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.
  4. description
    OS is defined as time from randomization to death from any cause
    measure
    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.
Full study description
brief Summary
The primary objective is, first, the comparison of tamoxifen and anastrozole and, second, the comparison of zoledronate added to standard adjuvant therapy with controls according to disease-free survival (DFS) in premenopausal patients with non-metastatic breast cancer treated with tamoxifen or anastrozole. To assess whether zoledronate added to standard adjuvant therapy can decrease or even prevent bone loss in patients treated with hormonal blockade combined with an antiestrogen or aromatase inhibitor.
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).
Source references
references
  1. citation
    Gnant M, Mlineritsch B, Luschin-Ebengreuth G, Kainberger F, Kassmann H, Piswanger-Solkner JC, Seifert M, Ploner F, Menzel C, Dubsky P, Fitzal F, Bjelic-Radisic V, Steger G, Greil R, Marth C, Kubista E, Samonigg H, Wohlmuth P, Mittlbock M, Jakesz R; Austrian Breast and Colorectal Cancer Study Group (ABCSG). Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy. Lancet Oncol. 2008 Sep;9(9):840-9. doi: 10.1016/S1470-2045(08)70204-3. Epub 2008 Aug 19.
    pmid
    18718815
    type
    BACKGROUND
  2. citation
    Gnant MF, Mlineritsch B, Luschin-Ebengreuth G, Grampp S, Kaessmann H, Schmid M, Menzel C, Piswanger-Soelkner JC, Galid A, Mittlboeck M, Hausmaninger H, Jakesz R; Austrian Breast and Colorectal Cancer Study Group. Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2007 Mar 1;25(7):820-8. doi: 10.1200/JCO.2005.02.7102. Epub 2006 Dec 11.
    pmid
    17159195
    type
    BACKGROUND
  3. citation
    Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Postlberger S, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, Samonigg H, Tausch C, Eidtmann H, Steger G, Kwasny W, Dubsky P, Fridrik M, Fitzal F, Stierer M, Rucklinger E, Greil R; ABCSG-12 Trial Investigators; Marth C. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 2009 Feb 12;360(7):679-91. doi: 10.1056/NEJMoa0806285.
    pmid
    19213681
    type
    BACKGROUND
  4. citation
    Gnant M, Dubsky P, Fitzal F, Blaha P, Schoppmann S, Steger G, Marth C, Samonigg H, Huttner K, Fohler H, Ruecklinger E, Jakesz R, Greil R; Austrian Breast and Colorectal Cancer Study Group. Maintaining bone density in patients undergoing treatment for breast cancer: is there an adjuvant benefit? Clin Breast Cancer. 2009 Jun;9 Suppl 1:S18-27. doi: 10.3816/CBC.2009.s.002.
    pmid
    19561003
    type
    BACKGROUND
  5. citation
    Gnant M. Can oral bisphosphonates really reduce the risk of breast cancer in healthy women? J Clin Oncol. 2010 Aug 1;28(22):3548-51. doi: 10.1200/JCO.2010.29.6327. Epub 2010 Jun 21. No abstract available.
    pmid
    20567005
    type
    BACKGROUND
  6. citation
    Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Heck D, Menzel C, Jakesz R, Seifert M, Hubalek M, Pristauz G, Bauernhofer T, Eidtmann H, Eiermann W, Steger G, Kwasny W, Dubsky P, Hochreiner G, Forsthuber EP, Fesl C, Greil R; Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol. 2011 Jul;12(7):631-41. doi: 10.1016/S1470-2045(11)70122-X. Epub 2011 Jun 5.
    pmid
    21641868
    type
    BACKGROUND
  7. citation
    Gnant M. Zoledronic acid in breast cancer: latest findings and interpretations. Ther Adv Med Oncol. 2011 Nov;3(6):293-301. doi: 10.1177/1758834011420599.
    pmid
    22084643
    type
    BACKGROUND
  8. citation
    Pfeiler G, Konigsberg R, Fesl C, Mlineritsch B, Stoeger H, Singer CF, Postlberger S, Steger GG, Seifert M, Dubsky P, Taucher S, Samonigg H, Bjelic-Radisic V, Greil R, Marth C, Gnant M. Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. J Clin Oncol. 2011 Jul 1;29(19):2653-9. doi: 10.1200/JCO.2010.33.2585. Epub 2011 May 9.
    pmid
    21555684
    type
    BACKGROUND
  9. citation
    Ressler S, Mlineritsch B, Greil R. Zoledronic acid for adjuvant use in patients with breast cancer. Expert Rev Anticancer Ther. 2011 Mar;11(3):333-49. doi: 10.1586/era.11.13.
    pmid
    21417849
    type
    BACKGROUND
  10. citation
    Hadji P, Coleman R, Gnant M, Green J. The impact of menopause on bone, zoledronic acid, and implications for breast cancer growth and metastasis. Ann Oncol. 2012 Nov;23(11):2782-2790. doi: 10.1093/annonc/mds169. Epub 2012 Jun 22.
    pmid
    22730099
    type
    BACKGROUND
  11. citation
    Rugani P, Luschin G, Jakse N, Kirnbauer B, Lang U, Acham S. Prevalence of bisphosphonate-associated osteonecrosis of the jaw after intravenous zoledronate infusions in patients with early breast cancer. Clin Oral Investig. 2014;18(2):401-7. doi: 10.1007/s00784-013-1012-5. Epub 2013 Jun 10.
    pmid
    23749244
    type
    BACKGROUND
  12. citation
    Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Knauer M, Moik M, Jakesz R, Seifert M, Taucher S, Bjelic-Radisic V, Balic M, Eidtmann H, Eiermann W, Steger G, Kwasny W, Dubsky P, Selim U, Fitzal F, Hochreiner G, Wette V, Sevelda P, Ploner F, Bartsch R, Fesl C, Greil R; Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12. Ann Oncol. 2015 Feb;26(2):313-20. doi: 10.1093/annonc/mdu544. Epub 2014 Nov 17.
    pmid
    25403582
    type
    BACKGROUND
Source notices and limitations
    Discovery and provenance
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        mparison of an AI with tamoxifen in premenopausal women):</p> <div class="pdq-content-list"><ol id="_3400"><li>In one study (<a href="/clinicaltrials/NCT00295646">NCT00295646</a>), 1,803 women who received goserelin were randomly assigned to a 2 &#215; 2 factorial design trial that compared anastrozole and tamoxifen,
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        n AI with tamoxifen in premenopausal women):</p> <div class="pdq-content-list"><ol id="_3400"><li>In one study (<a href="/clinicaltrials/NCT00295646">NCT00295646</a>), 1,803 women who received goserelin were randomly assigned to a 2 &#215; 2 factorial design trial that compared anastrozole and tamoxifen, with or witho
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      1. context
        Updated: April 25, 2025
        datetime
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    Preserved source evidence · Not medical advice