Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid

Austrian Breast & Colorectal Cancer Study Group

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: tamoxifen; Drug: anastrozole; Drug: zoledronic acid; Other: goserelin

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT00295646

CZOL 446 1B 01 (Other Identifier)

Zol-A-01 (Other Identifier)

ABCSG-12

Details and patient eligibility

About

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.

Full 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).

Enrollment: 1,803 patients

Sex: Female

Ages: 19 to 59 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,803 participants in 4 patient groups

AZ (Arimidex+Zoledronate)

Active Comparator group

Description:

Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid)

Treatment:

Other: goserelin

Drug: zoledronic acid

Drug: anastrozole

TZ (Tamoxifen+Zoledronate)

Active Comparator group

Description:

Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid)

Treatment:

Other: goserelin

Drug: zoledronic acid

Drug: tamoxifen

AC (Arimidex Control)

Active Comparator group

Description:

Study Drug Arimidex (Anastrozole)

Treatment:

Other: goserelin

Drug: anastrozole

TC (Tamoxifen Control)

Active Comparator group

Description:

Study Drug Nolvadex (Tamoxifen)

Treatment:

Other: goserelin

Drug: tamoxifen