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
18 Years
N/A
Female
Breast Cancer, Hypercalcemia of Malignancy, Metastatic Cancer, Pain
Trial Information
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.
Patients are followed at 24 weeks.
PROJECTED ACCRUAL: A total of 72 patients (18 per treatment arm) will be accrued for this
study.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care
Principal Investigator
Paula Silverman, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Case Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CWRU-080235
NCT ID:
NCT00060138
Start Date:
November 2002
Completion Date:
Related Keywords:
- Breast Cancer
- Hypercalcemia of Malignancy
- Metastatic Cancer
- Pain
- hypercalcemia of malignancy
- stage IV breast cancer
- recurrent breast cancer
- bone metastases
- pain
- Breast Neoplasms
- Neoplasms
- Hypercalcemia
- Neoplasm Metastasis
- Neoplasms, Second Primary
Name | Location |
|---|---|
| Ireland Cancer Center | Cleveland, Ohio 44106-5065 |
