Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid - Full Text View

Sponsor:	Austrian Breast & Colorectal Cancer Study Group
Collaborators:	AstraZeneca Novartis Pharmaceuticals
Information provided by (Responsible Party):	Austrian Breast & Colorectal Cancer Study Group
ClinicalTrials.gov Identifier:	NCT00295646

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Drug: tamoxifen Drug: anastrozole Drug: zoledronic acid	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid, in Premenopausal, Hormone Receptor-positive Breast Cancer Patients (Stage I, II)

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Tamoxifen Tamoxifen citrate Zoledronic acid Anastrozole

U.S. FDA Resources

Further study details as provided by Austrian Breast & Colorectal Cancer Study Group:

Primary Outcome Measures:

Comparison of tamoxifen with anastrozole in premenopausal patients with non-metastatic breast cancer and comparison of a subgroup additionally treated with zoledronate to a control subgroup without receiving zoledronate according to DFS. [ Time Frame: 28.05.2008 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

For the assessment of the recurrence free survival (RFS) patients receiving tamoxifen will be compared to patients receiving anastrozole and patients receiving zoledronate will be compared to controls, respectively. [ Time Frame: 28.05.2008 ] [ Designated as safety issue: No ]
For the assessment of the overall survival (OS) patients receiving tamoxifen will be compared to patients receiving anastrozole and patients receiving zoledronate will be compared to controls, respectively. [ Time Frame: 28.05.2008 ] [ Designated as safety issue: No ]
The objective is 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 anti-estrogen or aromatase inhibitor (AI). [ Time Frame: 28.05.2008 ] [ Designated as safety issue: No ]
Adverse and severe adverse events will be listed for all therapy subgroups "anastrozole / zoledronate" (AZ), "anastrozole / zoledronate control" (AC), "tamoxifen / zoledronate" (TZ), "tamoxifen / zoledronate control" (TC). [ Time Frame: 28.05.2008 ] [ Designated as safety issue: Yes ]

Enrollment:	1803
Study Start Date:	June 1999
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: AZ (Arimidex+Zoledronat) Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate)	Drug: anastrozole 1 mg/d Other Name: Arimidex Drug: zoledronic acid 4 mg q6m Other Name: Zoledronate, Zometa
Active Comparator: TZ (Tamoxifen+Zoledronate) Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate)	Drug: tamoxifen 20 mg/d Other Name: Nolvadex Drug: zoledronic acid 4 mg q6m Other Name: Zoledronate, Zometa
Active Comparator: AC (Arimidex Control) Study Drug Arimidex (Anastrozole)	Drug: anastrozole 1 mg/d Other Name: Arimidex
Active Comparator: TC (Tamoxifen Control) Study Drug Nolvadex (Tamoxifen)	Drug: tamoxifen 20 mg/d Other Name: Nolvadex

Detailed Description:

The trial is conducted as an open multi-center phase III study, in a two-factorial study design and according to 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 BMD measurements will be performed in a subgroup of patients (404 patients, enrolled in 3 centres).

Eligibility

Ages Eligible for Study:	19 Years to 59 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00295646

Show 73 Study Locations

Sponsors and Collaborators

Austrian Breast & Colorectal Cancer Study Group

AstraZeneca

Novartis Pharmaceuticals

Investigators

Principal Investigator:

Raimund Jakesz, MD

Austrian Breast & Colorectal Cancer Study Group

More Information

Additional Information:

Click here for more information about this study: ABCSG-Studien follow-up This link exits the ClinicalTrials.gov site

No publications provided by Austrian Breast & Colorectal Cancer Study Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2011 Jun 5.

Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Pöstlberger 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, Rücklinger 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.

Gnant M, Mlineritsch B, Luschin-Ebengreuth G, Kainberger F, Kässmann H, Piswanger-Sölkner 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, Mittlböck 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. Epub 2008 Aug 19.

Responsible Party:	Austrian Breast & Colorectal Cancer Study Group
ClinicalTrials.gov Identifier:	NCT00295646 History of Changes
Other Study ID Numbers:	ABCSG-12, CZOL 446 1B 01, Zol-A-01
Study First Received:	February 23, 2006
Last Updated:	January 30, 2012
Health Authority:	Austria: Federal Office for Safety in Health Care

Keywords provided by 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

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Anastrozole
Zoledronic acid
Diphosphonates
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses

Pharmacologic Actions
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents
Estrogen Antagonists
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012