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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00978926
Recruitment Status : Completed
First Posted : September 17, 2009
Last Update Posted : April 9, 2010
Information provided by:
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.

Condition or disease
Advanced Malignancy

Study Type : Observational
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Study of the Pharmacodynamic Effects of Anti-vascular Endothelial Growth Factor Therapy in Patients With Advanced Malignancies
Study Start Date : September 2009

Information from the National Library of Medicine

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

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


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:

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00978926

National University Hospital
Singapore, Singapore, 119074
Sponsors and Collaborators
National University Hospital, Singapore

Responsible Party: Ross Andrew Soo, National University Hospital, Singapore Identifier: NCT00978926     History of Changes
Other Study ID Numbers: MC02/15/07
First Posted: September 17, 2009    Key Record Dates
Last Update Posted: April 9, 2010
Last Verified: April 2010

Keywords provided by National University Hospital, Singapore:
Anti-Vascular Endothelial growth factor

Additional relevant MeSH terms:
Endothelial Growth Factors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Growth Substances
Physiological Effects of Drugs