RATIONALE: Comparing results of MRI scans done after bevacizumab may help doctors predict a patient's response to treatment and help plan the best treatment. It is not yet known whether giving bevacizumab alone is more effective than giving bevacizumab together with interferon alpha-2a in detecting kidney cancer. PURPOSE: This randomized phase II trial is studying MRI scans of blood vessel changes caused by bevacizumab to see how well it works compared with bevacizumab given together with interferon alpha-2a in treating patients with stage III or stage IV kidney cancer.
OBJECTIVES: Primary * To establish whether bevacizumab-induced changes in dynamic contrast-enhanced (DCE)-MRI vascular parameters are significantly enhanced by recombinant interferon alpha-2a. * To establish whether there is an interferon alpha-2a dose response in potentiating bevacizumab-induced changes in DCE-MRI vascular parameters. Secondary * To correlate changes in DCE-MRI vascular parameters for each treatment group with progression-free survival. * To correlate changes in DCE-MRI vascular parameters for each treatment group with tumor response and changes in tumor size. * To correlate changes in DCE-MRI vascular parameters for each treatment group with other surrogate biomarkers. * To assess the degree of change in baseline K\^trans within each arm of treatment. * To investigate changes in diffusion and blood oxygen-level dependent MRI and their correlation with other pharmacodynamic endpoints. * To assess the efficacy and safety profile of bevacizumab monotherapy or in combination with low or standard doses of recombinant interferon alpha-2a. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 3 treatment arms. * Arm I: Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks. * Arm II: Patients receive bevacizumab as in arm I and low-dose recombinant interferon alpha-2a subcutaneously (SC) 3 times weekly beginning on day 0. * Arm III: Patients receive bevacizumab as in arm I and standard-dose recombinant interferon alpha-2a SC 3 times weekly beginning on day 0. After 8 weeks of treatment, recombinant interferon alpha-2a dosage may be modified or discontinued at the discretion of the investigator. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo dynamic contrast-enhanced (gadopentetate dimeglumine) MRI scans at baseline and weeks 2 and 6. Peripheral blood and serum samples are collected at baseline and weeks 2, 6, and 8 for analysis of surrogate biomarkers by flow cytometry and mRNA analysis by PCR. Archival histopathological specimens are analyzed by IHC, fluorescence resonance-energy transfer, and fluorescence lifetime-imaging. Urine samples are also collected at baseline for proteomic profiling by MALDI-TOF. After completion of study treatment, patients are followed at 30 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
30
Given IV
Given SC
Addenbrooke's Hospital
Cambridge, England, United Kingdom
RECRUITINGRoyal Marsden - London
London, England, United Kingdom
RECRUITINGMount Vernon Cancer Centre at Mount Vernon Hospital
Northwood, England, United Kingdom
RECRUITINGChurchill Hospital
Oxford, England, United Kingdom
RECRUITINGRoyal Marsden - Surrey
Sutton, England, United Kingdom
RECRUITINGDynamic contrast-enhanced MRI defined changes in K-trans after 6 weeks of bevacizumab monotherapy or bevacizumab and low- or standard-dose recombinant interferon alpha-2a
Change in vascular permeability (K-trans) and tumor hypoxia at 2 and 6 weeks post-commencement of treatment
Best overall response
Progression-free survival
Time to progression
Treatment duration of bevacizumab and recombinant interferon alpha-2a
Treatment withdrawal
Dose modification
Incidence of adverse events
Number of circulating endothelial cells, circulating endothelial progenitors, and proangiogenic monocytic cells
Angiogenic factors (e.g., VEGF) and hypoxia-regulated markers
Correlation of DCE-MRI defined changes in K-trans with clinical response
Correlation of DCE-MRI defined changes in K-trans with surrogate biomarkers
Analysis of diffusion MRI and blood oxygen-level dependent MRI changes and comparison with other pharmacodynamic markers
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