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

Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00524849
• Other study ID #: CZOL446ECN05
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 4, 2007
• Last updated: September 13, 2010
• Start date: November 2006
• Est. completion date: January 2010

Study information

• Verified date: September 2010
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: January 2010
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bone Marrow Diseases
• Bone Metastases
• Bone Neoplasms
• Breast Neoplasms
• Metastatic Breast Cancer
• Neoplasm Metastasis

Intervention

Biological:
• Zoledronic acid
Zometa 1 mg weekly (intravenous)

Drug:
• Zoledronic acid
Zometa 4 mg every four weeks (intravenous)

Locations

Country	Name	City	State
China	Fudan University Cancer Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Fudan University	Novartis

Country where clinical trial is conducted

China, 

References & Publications (1)

Santini D, Vincenzi B, Dicuonzo G, Avvisati G, Massacesi C, Battistoni F, Gavasci M, Rocci L, Tirindelli MC, Altomare V, Tocchini M, Bonsignori M, Tonini G. Zoledronic acid induces significant and long-lasting modifications of circulating angiogenic factors in cancer patients. Clin Cancer Res. 2003 Aug 1;9(8):2893-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Circulating VEGF levels in breast cancer patients with bone metastases		one month	Yes
Secondary	Time to first skeletal-related event		3 years	No
Secondary	Time to bone progression disease		3 years	No
Secondary	Progression-free survival		3 years	No
Secondary	Overall survival		3 years	No