Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid

Phase 3

Completed

• Conditions: Breast Cancer
• Interventions: Drug: anastrozole; Drug: tamoxifen; Other: goserelin; Drug: zoledronic acid

• Registration Number: NCT00295646
• Lead Sponsor: Austrian Breast & Colorectal Cancer Study Group

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).

Study Timeline

• Study Start: 1999-06
• Study First Submitted: 2006-02-23
• Study First Submitted QC: 2006-02-23
• Study First Posted: 2006-02-24
• Primary Completion: 2008-03-27
• Study Completion: 2018-06-26
• Results First Submitted: 2023-07-31
• Status Verified: 2024-03
• Results First Submitted QC: 2024-03-13
• Last Update Submitted: 2024-03-13
• Results First Posted: 2024-03-15
• Last Update Posted: 2024-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 1803

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TC (Tamoxifen Control)	goserelin	Study Drug Nolvadex (Tamoxifen)
AZ (Arimidex+Zoledronate)	goserelin	Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid)
AC (Arimidex Control)	goserelin	Study Drug Arimidex (Anastrozole)
TZ (Tamoxifen+Zoledronate)	goserelin	Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid)
AZ (Arimidex+Zoledronate)	anastrozole	Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid)
AZ (Arimidex+Zoledronate)	zoledronic acid	Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid)
TZ (Tamoxifen+Zoledronate)	tamoxifen	Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid)
TZ (Tamoxifen+Zoledronate)	zoledronic acid	Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid)
AC (Arimidex Control)	anastrozole	Study Drug Arimidex (Anastrozole)
TC (Tamoxifen Control)	tamoxifen	Study Drug Nolvadex (Tamoxifen)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Comparison of Zoledronate vs no Zoledronate in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Recurrence-free Survival (RFS)	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.	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
Comparison of Anastrozole vs Tamoxifen in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Recurrence-free Survival (RFS)	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.	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
Comparison of Anastrozole vs Tamoxifen in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Overall Survival (OS)	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.	OS is defined as time from randomization to death from any cause
Comparison of Zoledronate vs no Zoledronate in Premenopausal Patients With Non-metastatic Breast Cancer With Respect to Overall Survival (OS)	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.	OS is defined as time from randomization to death from any cause

Trial Locations

Locations (72)

Hospital of Guessing; 🇦🇹 Guessing, Burgenland, Austria

Hospital Oberpullendorf; 🇦🇹 Oberpullendorf, Burgenland, Austria

Hospital Oberwart; 🇦🇹 Oberwart, Burgenland, Austria

State Hospital Klagenfurt, Surgery; 🇦🇹 Klagenfurt, Carinthia, Austria

State Hospital Klagenfurt; 🇦🇹 Klagenfurt, Carinthia, Austria

Hospital BHB St. Veit; 🇦🇹 St. Veit a. d. Glan, Carinthia, Austria

Ordination Dr. Wette; 🇦🇹 St. Veit a. d. Glan, Carinthia, Austria

State Hospital Villach; 🇦🇹 Villach, Carinthia, Austria

Privat Hospital Villach; 🇦🇹 Villach, Carinthia, Austria

State Hospital Wolfsberg; 🇦🇹 Wolfsberg, Carinthia, Austria

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