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

Fudan University

Status and phase: Completed; Phase 3; Phase 2

Conditions: Metastatic Breast Cancer; Bone Metastases

Treatments: Drug: Zoledronic acid

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00524849

CZOL446ECN05

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 60 patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

conventional Zometa

Active Comparator group

Description:

Zometa 4mg IV q4w, in combination with other antitumor agents one month after the initial dosing.

Treatment:

Drug: Zoledronic acid

Drug: Zoledronic acid

weekly Zometa

Experimental group

Description:

Weekly Zometa in combination with other antitumor agents one month after the initial dosing.