Conditions: Breast Cancer
Keywords: 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
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1803
Healthy volunteers: no

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).

Arms:
arm 1: Study Drugs Arimidex (Anastrozole), Zometa (Zoledronate; zoledronic acid) arm 2: Study Drugs Nolvadex (Tamoxifen), Zometa (Zoledronate; zoledronic acid) arm 3: Study Drug Arimidex (Anastrozole) arm 4: Study Drug Nolvadex (Tamoxifen)

Interventions: intervention 1: tamoxifen intervention 2: anastrozole intervention 3: zoledronic acid intervention 4: goserelin
Intervention descriptions: intervention 1: 20 mg/d intervention 2: 1 mg/d intervention 3: 4 mg q6m intervention 4: 3.6 mg goserelin subcutaneously every 28 days

Protocol document: