Sorafenib and Bevacizumab in Treating Patients With Advanced Kidney Cancer
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Bevacizumab and sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with bevacizumab may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of sorafenib and bevacizumab and to see how well they work in treating patients with advanced kidney cancer.
Drug: sorafenib tosylate
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Trial of BAY 43-9006 in Combination With Bevacizumab in Patients With Advanced RenalCancer|
- Toxicity (Phase I) [ Time Frame: 30 days after last chemotherapy treatment ] [ Designated as safety issue: Yes ]
- Progression-free survival (Phase II) [ Time Frame: Off-study date ] [ Designated as safety issue: No ]
|Study Start Date:||May 2005|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Sorafenib and bevacizumab
Given through a vein in the arm 1 time every 2 weeks.Drug: sorafenib tosylate
Will be take by mouth twice a day.
- Determine the tolerability and maximum tolerated dose of sorafenib and bevacizumab in patients with advanced renal cell cancer. (Phase I)
- Determine the progression-free survival of patients treated with this regimen. (Phase II)
- Determine the median time to progression in patients treated with this regimen. (Phase II)
- Determine the number and percent of patients with stable disease at 6 months after treatment with this regimen. (Phase II)
- Determine the objective response rate and duration of objective response in patients treated with this regimen. (Phase II)
- Determine the number of complete and partial responses in patients treated with this regimen. (Phase II)
- Correlate changes in tumor perfusion and vascular permeability by serial dynamic contrast-enhanced MRI or arterial spin labeled MRI with antitumor effects of this regimen and clinical outcome in these patients. (Phase II)
- Determine the effect of this regimen on circulating endothelial cells and progenitors as an indicator of angiogenic effects in these patients. (Phase II)
- Correlate steady-state trough plasma concentrations of these drugs with toxicity and clinical activity in these patients. (Phase II)
OUTLINE: This is an open-label, multicenter, phase I dose-escalation study followed by a phase II study.
- Phase I: Patients receive oral sorafenib twice daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of sorafenib and bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD.
- Phase II: Patients receive oral sorafenib once daily on days 1-28 and bevacizumab IV over 90 minutes on days 1 and 15 at the MTD in the absence of disease progression or unacceptable toxicity*.
NOTE: *Patients may remain on protocol if only 1 of the drugs is stopped.
- After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 32-58 patients (12-18 for the phase I portion and 20-40 for the phase II portion) will be accrued for this study within approximately 5-19 months.
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104-4283|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center - Cool Springs|
|Nashville, Tennessee, United States, 37064|
|Vanderbilt-Ingram Cancer Center at Franklin|
|Nashville, Tennessee, United States, 37064|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232-6838|
|Study Chair:||Jeffrey A. Sosman, MD||Vanderbilt-Ingram Cancer Center|