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

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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

Condition or disease
Hypertension; Proteinuria

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.

Study Design

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Study Type :	Observational
Time Perspective:	Prospective
Official Title:	A Study of the Pharmacodynamic Effects of Anti-Vascular Endothelial Growth
Study Start Date :	August 2007
Actual Primary Completion Date :	May 2010
Actual Study Completion Date :	May 2010

Groups and Cohorts

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Group/Cohort

patients on anti-VEGF therapy; 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.

Outcome Measures

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Primary Outcome Measures :

1. Effect of VEGF on endothelial function and on retinal microvasculature and the pulmonary function of patients with malignancy (primary or secondary) involving the lung. [ Time Frame: until 4 weeks after end of treatment ]

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	21 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Those who are starting on anti-VEGF therapy (such as but not limited to bevacizumab, sunitinib, and sorafenib) as part of routine clinical management

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:

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Singapore
National University Hospital
Singapore, Singapore

Sponsors and Collaborators

National University Hospital, Singapore

Investigators

Principal Investigator:	Ross Andrew Soo, MBBS, MRCP	National University Hospital, Singapore

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Kasahara Y, Tuder RM, Taraseviciene-Stewart L, Le Cras TD, Abman S, Hirth PK, Waltenberger J, Voelkel NF. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest. 2000 Dec;106(11):1311-9.

Veronese ML, Mosenkis A, Flaherty KT, Gallagher M, Stevenson JP, Townsend RR, O'Dwyer PJ. Mechanisms of hypertension associated with BAY 43-9006. J Clin Oncol. 2006 Mar 20;24(9):1363-9. Epub 2006 Jan 30.

Responsible Party:	National University Hospital, Singapore
ClinicalTrials.gov Identifier:	NCT00698659 History of Changes
Other Study ID Numbers:	MC2/15/07
First Posted:	June 17, 2008
Last Update Posted:	December 11, 2013
Last Verified:	April 2012

Additional relevant MeSH terms:

Proteinuria; Urination Disorders; Urologic Diseases; Urological Manifestations	Signs and Symptoms; Endothelial Growth Factors; Growth Substances; Physiological Effects of Drugs