A Phase I-II, 24-Week, Multi-Center, Double-Blind, Randomized, Dose-Ranging Study To Evaluate The Safety And Efficacy Of A Humanized Monoclonal Antibody To PTHrP Versus Zoledronic Acid In Patients With Breast Cancer Metastatic To Bone

OBJECTIVES:

• Compare the safety and tolerability of monoclonal antibody CAL vs zoledronate in women with breast cancer and bone metastases.
• Compare, preliminarily, the potential effects of these drugs on skeletal events/manifestations related to bone metastases, including hypercalcemia, bone pain, bone metastatic lesions, complications (e.g., pathologic fracture and spinal cord compression), and interventions (e.g., surgery and radiotherapy) in these patients.
• Compare changes in ECOG performance status in patients treated with these drugs.
• Determine the pharmacokinetics of monoclonal antibody CAL in these patients.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to average prestudy pain score on question 3 of a daily electronic telephone pain diary (less than 3 vs 3 or more) and prior bisphosphonate therapy (yes vs no). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive monoclonal antibody CAL IV over 30-60 minutes on day 1.
• Arm II: Patients receive a lower dose of monoclonal antibody CAL as in arm I.
• Arm III: Patients receive a lower dose (lower than arm II) of monoclonal antibody CAL as in arm I.
• Arm IV: Patients receive zoledronate IV over 30-60 minutes on day 1. Treatment in all arms repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients keep a pain diary throughout study participation.