Phase II Trial of Sorafenib (BAY 43-9006) (IND 69896; NSC 724772) in Patients With Advanced Urothelial Cancer
I. To evaluate the 4-month progression-free survival rate, response rate and toxicity of BAY
43-9006 in patients with progressing regional or metastatic transitional cell carcinoma (or
mixed histologies containing a component of TCC) of the urothelium who have progressed on
one and only one prior systemic chemotherapy regimen for metastatic disease.
I. To determine the time to disease progression and overall survival with BAY 43-9006.
II. To evaluate the frequency of polymorphisms in drug metabolizing enzymes and to correlate
these polymorphisms with variations in BAY 43-9006 pharmacokinetics.
III. To evaluate the frequency of raf kinase mutations in tumor specimens and correlate
these with response rate.
IV. To evaluate serum VEGF levels as potential markers of angiogenesis inhibition by BAY
V. To evaluate markers of apoptosis and kinase inhibition in peripheral blood mononuclear
cells as potential biomarkers of BAY 43-9006 activity.
VI. To determine if there are proteins differentially translated from the genome in patients
who respond to treatment with BAY 43-9006 versus patients who do not respond to BAY 43-9006.
OUTLINE: This is a multicenter study.
Patients receive oral sorafenib twice daily on days 1-56. Courses repeat every 56 days in
the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months until 2 years from
study entry and then every 6 months until 3 years from study entry.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Kaplan-Meier Estimate of Progression-free Survival at 4 Months
Survival estimate from the Kaplan-Meier curve of the proportion of patients alive and progression-free at 4 months. Progression-free survival is defined as the time from registration to progression or death, whichever occurs first. Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions.
Assessed every cycle while on treatment; after being off-treatment, assessed every 3 months for 2 years, then every 6 months for 1 year.
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
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