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

December 10, 2013 updated by: National University Hospital, Singapore

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

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

Study Overview

Status

Terminated

Conditions

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 Type

Observational

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Singapore
- - Singapore, Singapore
    - National University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Time Perspectives: Prospective

Number of groups / cohorts

Cohorts and Interventions

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.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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. Time Frame: until 4 weeks after end of treatment	until 4 weeks after end of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University Hospital, Singapore

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

May 1, 2010

Study Completion (Actual)

May 1, 2010

Study Registration Dates

First Submitted

June 15, 2008

First Submitted That Met QC Criteria

June 16, 2008

First Posted (Estimate)

June 17, 2008

Study Record Updates

Last Update Posted (Estimate)

December 11, 2013

Last Update Submitted That Met QC Criteria

December 10, 2013

Last Verified

April 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

MC2/15/07

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