Zometa and Circulating Vascular Endothelial Growth Factor (VEGF) in Breast Cancer Patients With Bone Metastasis

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the effects of Zometa (zoledronic acid, 1 mg per week versus 4 mg every four weeks) on the circulating vascular endothelial growth factor (VEGF) levels in breast cancer patients with bone metastases. Sixty patients will be randomized into two groups.

Detailed Description
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The administration of Zometa in short intervals has been implied to be more potent in maximizing its antitumor and antiangiogenesis effects, while dosing every four weeks is an appropriate strategy for the prevention and management of bone metastases. This study was designed to explore the relationship between dosing of Zometa and level of circulating VEGF.

Official Title
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Randomized Phase 2 Study on the Relationship Between Circulating VEGF and Weekly or Every-four-week Zometa in Breast Cancer Patients With Bone Metastases

Conditions
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Metastatic Breast Cancer, Bone Metastases

Intervention / Treatment
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* Biological: Zoledronic acid
* Drug: Zoledronic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Female, 18 years or older Histologically confirmed invasive breast cancer Bone metastases ECOG Performance Status of 0 to 2 Life expectancy of more than 3 months Subject must have adequate organ function: Cr ≤ 3 mg/dL (265 µmol/L)， CrCl (Cockcroft & Gault) ≥ 30 mL/min， Ca2+ > 8.0 mg/dL (2.0 mmol/L) and ≤ 12 mg/dL (3.0 mmol/L) Negative serum pregnancy test for women with childbearing potential Good conditions for infusion and willing to undergo phlebotomy during the whole study Have ceased anti-tumor treatment including chemotherapy, endocrinotherapy and bio-targeted therapy for over 28 days Exclusion Criteria: Pregnant or lactating females History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety Active or uncontrolled infection Current active dental problems including infection of the teeth or jawbone (maxilla or mandible); dental or fixture trauma; or a current or prior diagnosis of osteonecrosis of the jaw (ONJ); or exposed bone in the mouth; or slow healing after dental procedures Recent (within 6 weeks of Randomization) or planned dental or jaw surgery (e.g. extraction, implants) Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure Concomitant with liver, brain or symptomatic lung metastases (symptoms such as hemoptysis, severe cough and shortness of breath) Accepted radiotherapy for solitary bone disease within 30 days before study Previous treatment with other bisphosphonates or radionuclides within one month before study Known hypersensitivity to bisphosphonates History of treatment with calcitonin, gallium nitrate or mithracin within 14 days before study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: conventional Zometa<br>Zometa 4mg IV q4w, in combination with other antitumor agents one month after the initial dosing. | Drug: Zoledronic acid<br>* Zometa 4 mg every four weeks (intravenous)<br>|
| Experimental: weekly Zometa<br>Weekly Zometa in combination with other antitumor agents one month after the initial dosing. | Biological: Zoledronic acid<br>* Zometa 1 mg weekly (intravenous)<br>* Other names: Zometa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating VEGF levels in breast cancer patients with bone metastases |  | one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first skeletal-related event |  | 3 years | 
| Time to bone progression disease |  | 3 years | 
| Progression-free survival |  | 3 years | 
| Overall survival |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Bone metastasis, Circulating VEGF, Zoledronic acid, Angiogenesis