Monoclonal Antibody Compared With Zoledronate in Treating Women With Breast Cancer and Bone Metastases

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.

Patients are followed at 24 weeks.

PROJECTED ACCRUAL: A total of 72 patients (18 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer
• Radiographical evidence of at least 1 bone metastasis

• No prior radiotherapy or surgery to bone metastasis
• No radiotherapy or surgery anticipated for bone metastasis within the next 24 weeks
• Bone pain severity score of at least 1 on 5 of 7 days as determined by question 3 of the Brief Pain Inventory (BPI)
• No bone metastases to a weight-bearing bone at imminent risk for pathologic fracture or surgical intervention
• No vertebral metastases that place the patient at imminent risk of spinal cord compression
• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Pre- or post-menopausal

Performance status

• ECOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

• WBC at least 2,000/mm^3
• Lymphocyte count at least 500/mm^3
• Granulocyte count at least 1,000/mm^3
• Platelet count at least 50,000/mm^3

Hepatic

• ALT or AST no greater than 2.5 times upper limit of normal (ULN)
• Bilirubin no greater than 1.5 times ULN

Renal

• Calcium no greater than 10.1 mg/dL
• No oliguria, defined as less than 30 mL urine per 2-hour collection
• No acute renal failure
• Creatinine no greater than 2.5 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No sepsis
• No known or anticipated contraindication to study drugs

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 3 weeks since initiation of a new chemotherapy regimen

Endocrine therapy

• More than 3 weeks since initiation of a new hormonal therapy regimen

Radiotherapy

• See Disease Characteristics
• More than 3 weeks since prior radiotherapy

Surgery

• See Disease Characteristics

Other

• More than 60 days since prior bisphosphonates
• More than 30 days since prior investigational drugs
• No change in analgesic drug regimen during the screening period