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

Sponsor
National University Hospital, Singapore (Other)
Overall Status
Terminated
CT.gov ID
NCT00698659
Collaborator
(none)
1
Location
33
Duration (Months)

Study Details

Study Description

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 Intervention/Treatment Phase

    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

    Study Type:
    Observational
    Time Perspective:
    Prospective
    Official Title:
    A Study of the Pharmacodynamic Effects of Anti-Vascular Endothelial Growth
    Study Start Date :
    Aug 1, 2007
    Actual Primary Completion Date :
    May 1, 2010
    Actual Study Completion Date :
    May 1, 2010

    Arms and Interventions

    Arm Intervention/Treatment
    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

    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. [until 4 weeks after end of treatment]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National University Hospital Singapore Singapore

    Sponsors and Collaborators

    • National University Hospital, Singapore

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    National University Hospital, Singapore
    ClinicalTrials.gov Identifier:
    NCT00698659
    Other Study ID Numbers:
    • MC2/15/07
    First Posted:
    Jun 17, 2008
    Last Update Posted:
    Dec 11, 2013
    Last Verified:
    Apr 1, 2012
    Additional relevant MeSH terms:
    Proteinuria

    Study Results

    No Results Posted as of Dec 11, 2013