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

Study Overview
=================
Brief Summary
-----------------
To determine the effect of anti-vascular endothelial growth factor (VEGF) on endothelial function and on retinal microvasculature 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 To characterize the effect of anti-VEGF therapy on the pulmonary function of patients with malignancy (primary or secondary) involving the lung

Detailed 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.

Official Title
-----------------
A Study of the Pharmacodynamic Effects of Anti-Vascular Endothelial Growth

Conditions
-----------------
Hypertension, Proteinuria

Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients on anti-VEGF therapy<br>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. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of VEGF on endothelial function and on retinal microvasculature and the pulmonary function of patients with malignancy (primary or secondary) involving the lung. |  | until 4 weeks after end of treatment |