Bevacizumab and Sorafenib in Treating Patients With Recurrent Glioblastoma Multiforme
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving bevacizumab together with sorafenib may kill more tumor cells.
PURPOSE: This phase II trial is studying the side effects and how well giving bevacizumab together with sorafenib works in treating patients with recurrent glioblastoma multiforme.
Brain and Central Nervous System Tumors
Drug: sorafenib tosylate
Other: flow cytometry
Other: immunoenzyme technique
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Bevacizumab in Combination With Sorafenib in Recurrent Glioblastoma Multiforme|
- 6-month progression-free survival [ Designated as safety issue: No ]
- Safety, toxicity, and adverse events [ Designated as safety issue: Yes ]
- Time to progression [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Quality of life as assessed by the FACT-Br at baseline, prior to every other treatment course, and at the end of treatment [ Designated as safety issue: No ]
- Utility of dynamic contrast-enhanced MRI as a predictor of response [ Designated as safety issue: No ]
- Relationship between tumor biomarkers and circulating biomarkers of vascular response and clinical outcome [ Designated as safety issue: No ]
|Study Start Date:||September 2008|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
- Identify the clinical efficacy of bevacizumab and sorafenib, as measured by 6-month progression-free survival, in patients with recurrent glioblastoma multiforme.
- Assess the safety and toxicity of this regimen in this patient population.
- Assess time to progression and overall survival of this patient population.
- Assess the utility of dynamic contrast-enhanced MRI as a predictor of response to this treatment regimen.
- Determine the relationship between tumor biomarkers and circulating biomarkers of vascular response and clinical outcome in patients treated with this regimen.
- Assess the impact of treatment on the patient's quality of life using the FACTBr.
- Bank leftover tissue and blood products (i.e., plasma, DNA, and buffy coat) for future research studies.
OUTLINE: This is a multicenter study.
Patients receive oral sorafenib once daily on days 1-14 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood and plasma sample collection at baseline and then periodically during study treatment for translational research studies. Translational research studies include analysis of circulating endothelial cells and circulating endothelial progenitor cells by flow cytometry and measurement of angiogenic proteins in plasma by ELISA. DNA and buffy coat are extracted and collected from the blood samples for pharmacogenetic studies.
Quality of life is assessed at baseline, prior to every other treatment course, and at the end of treatment.
After completion of study treatment, patients are followed at 28-42 days, every 3 months for 5 years, and then annually for 10 years.