A Phase I/II Trial of BAY 43-9006 in Combination With Bevacizumab in Patients With Advanced RenalCancer
- 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
- Determine the median time to progression in patients treated with this regimen. (Phase
- 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
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.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) of BAY 43-9006 (Sorafenib)in Combination With Bevacizumab (Phase I)
The highest dose in milligrams (mg) of BAY 43-9006 (Sorafenib) in combination with Bevacizumab while maintaining tolerability. Cohorts of 3-6 patients received escalating doses of sorafenib and bevacizumab until the maximum tolerated dose (MTD) was achieved. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity during the initial cycle of therapy. DLTs include absolute neutrophil count (ANC) < 500/mm3 for > 7 days, ANC < 1000/mm3 with fever > 101 degrees Fahrenheit, platelet count < 50,000 mm3, and non-hematologic toxicity Common Toxicity Criteria (CTC) >= Grade 3.
at 28 days
Jeffrey A. Sosman, MD
Vanderbilt-Ingram Cancer Center
United States: Food and Drug Administration
VICC URO 0470
|Beth Israel Deaconess Medical Center||Boston, Massachusetts 02215|
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|Vanderbilt-Ingram Cancer Center - Cool Springs||Nashville, Tennessee 37064|
|Vanderbilt-Ingram Cancer Center at Franklin||Nashville, Tennessee 37064|