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
|ClinicalTrials.gov Identifier: NCT00873236|
Recruitment Status : Unknown
Verified March 2009 by National Cancer Institute (NCI).
Recruitment status was: Recruiting
First Posted : April 1, 2009
Last Update Posted : August 12, 2013
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.
|Condition or disease||Intervention/treatment||Phase|
|Kidney Cancer||Biological: bevacizumab Biological: recombinant interferon alpha-2a||Phase 2|
- 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.
- 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 (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Masking:||None (Open Label)|
|Official Title:||Dynamic Contrast Enhanced MRI (DCE-MRI) Assessment of the Vascular Changes Induced With Bevacizumab Alone and in Combination With Interferon-α in Patients With Advanced Renal Cell Carcinoma|
|Study Start Date :||April 2008|
Experimental: Arm I
Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks.
Experimental: 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.
Given IVBiological: recombinant interferon alpha-2a
Experimental: Arm III
Patients receive bevacizumab as in arm I and standard-dose recombinant interferon alpha-2a SC 3 times weekly beginning on day 0.
Given IVBiological: recombinant interferon alpha-2a
- 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
- 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00873236
|Cambridge, England, United Kingdom, CB2 2QQ|
|Contact: Contact Person 44-1223-245-151|
|Royal Marsden - London||Recruiting|
|London, England, United Kingdom, SW3 6JJ|
|Contact: Contact Person 44-20-7352-8171|
|Mount Vernon Cancer Centre at Mount Vernon Hospital||Recruiting|
|Northwood, England, United Kingdom, HA6 2RN|
|Contact: Paul Nathan, MD 44-192-384-4966|
|Oxford, England, United Kingdom, OX3 7LJ|
|Contact: Contact Person 44-186-574-1841|
|Royal Marsden - Surrey||Recruiting|
|Sutton, England, United Kingdom, SM2 5PT|
|Contact: Contact Person 44-20-8642-6011|
|Principal Investigator:||Paul Nathan, MD||Mount Vernon Cancer Centre at Mount Vernon Hospital|