Pharmacokinetic and Phase I Study of Sorafenib (BAY 43-9006, NSC 724772, IND 69896) for Solid Tumors and Hematologic Malignancies in Patients With Hepatic or Renal Dysfunction
I. To characterize the pharmacokinetics of BAY 43-9006 in patients with hepatic or renal
dysfunction (part 1 of the study).
II. To determine a tolerable starting dose of BAY 43-9006 in patients with varying degrees
of hepatic or renal dysfunction (part 2 of the study).
OUTLINE: This is a dose-escalation, multicenter study. Patients are assigned to 1 of 9
treatment cohorts according to hepatic or renal function.
Patients receive oral sorafenib once on day 1 and then once daily, twice daily, or every
other day beginning on day 8 and continuing for 3 months. Patients are re-evaluated at 3
months. Patients with responding disease may continue study treatment in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-6 patients (per treatment cohort) receive escalating doses of sorafenib until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding
that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6
patients are treated at the MTD.
PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.
Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Relationship between the pharmacokinetics and measures of renal dysfunction categorized by creatinine clearance as estimated by the Cockcroft and Gault formula (Part 1)
Explored using standard parametric and non-parametric methods for one- and two-way analysis of variance (ANOVA) layouts (the dysfunction factor (hepatic/renal) and the severity factor (mild, moderate, severe, very severe).
Prior to and at 1, 2, 3, 4, 6, and 24 hours post-dose on day 1
Cancer and Leukemia Group B
United States: Food and Drug Administration
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