Comparison of Two Schedules of Zoledronic Acid in Treating Patients With Breast Cancer That Has Spread to the Bone

• Fractures
  
• Radiotherapy to bone either for relief of pain or to treat or prevent pathological fractures or spinal cord compression
  
• Hypercalcemia of malignancy
  
• Orthopedic surgery to prevent or treat pathological fractures or spinal cord compression
  
• Spinal cord compression
  

• Quality of life as measured by QLQ-C30 and the QLQ-BR23 breast-specific module
  
• Clinical burden of skeletal complications
  
• Pain, performance status, and analgesic use
  
• Incidence of new bone metastases
  
• Overall survival
  
• Bisphosphonate use and expenditure on administration
  
• Health care utilization
  
• Clinical utility of the "point of care" test for N-telopeptides (NTx) excretion
  

OBJECTIVES:

Primary

• Compare the frequency and timing of serious related events (e.g., fractures, radiotherapy to bone, hypercalcemia of malignancy, orthopedic surgery, and spinal cord compression) in patients with advanced breast cancer metastatic to the bone treated with bone marker-directed schedule vs standard schedule zoledronic acid.

Secondary

• Compare the quality of life of patients treated with these regimens.
• Compare the clinical burden of skeletal complications in these patients.
• Compare pain, performance status, and analgesic use (PPA score) in these patients.
• Compare the incidence of new bone metastases in these patients.
• Compare overall survival of these patients.
• Compare bisphosphonate use and expenditure on administration in these patients.

OUTLINE: This is an open-label, randomized, controlled, parallel-group, multicenter study. Patients are stratified according to treatment center, gender, type of concurrent systemic therapy at study entry (endocrine therapy [with or without trastuzumab (Herceptin^®)] vs chemotherapy [with or without trastuzumab] vs trastuzumab alone vs chemotherapy and endocrine therapy [with or without trastuzumab] vs no systemic anticancer treatment), prior skeletal-related event (yes vs no), duration of bisphosphonate use for metastatic disease prior to study entry (4-6 months vs 6-12 months), type of metastases present at study entry (bone only vs bone and soft tissue vs bone and visceral metastases vs bone, soft tissue, and visceral metastases). Patients are randomized to 1 of 2 treatment arms.

• Arm I (standard schedule): Patients receive zoledronic acid IV over 15 minutes once every 3-4 weeks for 24 months.
• Arm II (bone marker-directed schedule): Patients receive zoledronic acid IV over 15 minutes once every 3-4, 8-9, or 15-16 weeks (based on serum N-telopeptide:creatinine ratio) for 24 months.

Quality of life is assessed at baseline and at 3, 6, 9, 12, 18, and 24 months.

After completion of study therapy, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 1,500 patients will be accrued for this study.