A Study of the Pharmacodynamic Effects of Anti-Vascular Endothelial Growth Factor Therapy in Patients With Advanced Malignancies

Completed

• Conditions: Advanced Malignancy

• Registration Number: NCT00978926
• Lead Sponsor: National University Hospital, Singapore

Brief Summary

The well-established role of vascular endothelial growth factor (VEGF) in carcinogenesis and tumor angiogenesis has led to the development of agents that target this pathway. Anti-VEGF agents the VEGF monoclonal antibody bevacizumab, and the small molecule VEGF receptor tyrosine kinase inhibitors. Angiogenic factors play a key role in the maintenance of lung integrity and normal endothelial function. Endothelial dysfunction has been implicated in hypertension, proteinuria and retinopathy. One of the major issues of anti-VEGF agents is its long-term toxicity especially taking into account the lack of adequate knowledge in this area and the possibility of prolonged periods of therapy in non-progressing patients. Hypertension and proteinuria are commonly seen in patients treated with anti-VEGF agents. In addition, the investigators have also observed in a relatively high frequency of pulmonary air-filled lesions in patients with malignancy in the lung treated with an anti-VEGF agent. Objectives of this exploratory study are to 1) determine the effect of anti-vascular endothelial growth factor (VEGF) on endothelial function 2) determine endothelial dysfunction as a marker of early response and as an indicator for the development of hypertension and proteinuria 3) characterize the effect of anti-VEGF therapy on the pulmonary function of patients with malignancy (primary or secondary) involving the lung in patients treated with anti-VEGF agents. Pharmacodynamic endpoints to be assessed are: blood pressure, brachial artery reactivity, retinal microvessels, microalbuminuria and proteinuria, pulmonary function, assess the effects of anti-VEGF therapy by assessing brachial artery reactivity, retinal vasculature and pulmonary function in a subset of patients receiving anti-VEGF therapy. The development of markers of endothelial dysfunction may result in the early identification of patients who are non-responders or develop toxicity from anti-VEGF treatment.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-06-19
• Study Start: 2009-09
• Study First Submitted QC: 2009-09-16
• Study First Posted: 2009-09-17
• Status Verified: 2010-04
• Last Update Submitted: 2010-04-08
• Last Update Posted: 2010-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Eligibility
• Patients who are receiving single agent anti-VEGF therapy
• Signed written informed consent
• Patients with measurable pulmonary malignancy (primary or metastatic) as determined by RECIST will undergo assessment of pulmonary function
• Patients with a known allergy to intravenous contrast used in fluorescein and indocyanine green angiography will be exempt from these investigations but will undergo other study assessments

Exclusion Criteria

• None

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Trial Locations

Locations (1)

National University Hospital; 🇸🇬 Singapore, Singapore