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

National University Health System (NUHS)

Status: Terminated

Conditions: Hypertension; Proteinuria

Study type: Observational

Funder types: Other

Identifiers

NCT00698659

MC2/15/07

Details and patient eligibility

About

1. To determine the effect of anti-vascular endothelial growth factor (VEGF) on endothelial function and on retinal microvasculature
2. To determine endothelial dysfunction as a marker of early response and as an indicator for the development of hypertension and proteinuria in patients treated with anti-VEGF agents
3. To characterize the effect of anti-VEGF therapy on the pulmonary function of patients with malignancy (primary or secondary) involving the lung

Full description

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, we 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.

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Trial design

0 participants in 1 patient group

patients on anti-VEGF therapy

Description:

This study aims to assess the pharmacodynamic effects of anti-VEGF therapy. The following groups of patients will be approached: Those who are starting on anti-VEGF therapy (such as but not limited to bevacizumab, sunitinib, and sorafenib) as part of routine clinical management or on clinical studies All patients must be aged aged ≥ 21 years All patients must have a signed written informed consent prior to study enrollment. A separate consent will be obtained from patients already involved in a clinical study using anti-VEGF treatment. 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.