MRI Scans of Blood Vessel Changes Caused by Bevacizumab Alone or Given Together With Interferon Alpha-2a in Treating Patients With Stage III or Stage IV Kidney Cancer
- Conditions
- Kidney Cancer
- Interventions
- Biological: bevacizumabBiological: recombinant interferon alpha-2a
- Registration Number
- NCT00873236
- Lead Sponsor
- Mount Vernon Cancer Centre at Mount Vernon Hospital
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Arm I bevacizumab Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks. Arm II bevacizumab Patients receive bevacizumab as in arm I and low-dose recombinant interferon alpha-2a subcutaneously (SC) 3 times weekly beginning on day 0. Arm II recombinant interferon alpha-2a 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 bevacizumab Patients receive bevacizumab as in arm I and standard-dose recombinant interferon alpha-2a SC 3 times weekly beginning on day 0. Arm III recombinant interferon alpha-2a Patients receive bevacizumab as in arm I and standard-dose recombinant interferon alpha-2a SC 3 times weekly beginning on day 0.
- Primary Outcome Measures
Name Time Method Dynamic 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
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (5)
Royal Marsden - Surrey
🇬🇧Sutton, England, United Kingdom
Mount Vernon Cancer Centre at Mount Vernon Hospital
🇬🇧Northwood, England, United Kingdom
Royal Marsden - London
🇬🇧London, England, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, England, United Kingdom
Churchill Hospital
🇬🇧Oxford, England, United Kingdom