Phase I Pharmacokinetic Study of Dasatinib (BMS-354825) (NSC-732517; IND-73969) in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction
I. To estimate the maximum tolerated dose of dasatinib in patients with varying degrees of
II. To estimate the pharmacokinetic (PK) profile of this drug in these patients.
III. To assess the safety profile and dose-limiting toxicities (if any) of this drug in
I. To describe any antitumor efficacy associated with this drug in these patients.
II. To examine whether the PK clearance of dasatinib correlates with hepatic function as
assessed by Child-Pugh Criteria, the NCI Organ Dysfunction Working Group Criteria, or other
assessments of liver function such as total bilirubin level.
OUTLINE: This is a multicenter study. Patients are stratified according to hepatic function
as defined by the Child-Pugh classification system (control [i.e., total bilirubin normal,
AST/ALT normal, and PT normal, and Child-Pugh classification score of 5] vs mild impairment
[Child-Pugh class A] vs moderate impairment [Child-Pugh class B] vs severe impairment
[Child-Pugh class C]).
Patients receive dasatinib orally (PO) once daily on days 1-28. Courses repeat every 28 days
in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating dose of dasatinib 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.
Patients undergo blood sample collection on days 1 and 8 of course 1 for pharmacokinetic
After completion of study treatment, patients are followed periodically for 28 days.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose, defined as the highest dose level at which less than 33% of 6-9 evaluable patients experience DLT
Toxicity will graded according to the NCI CTCAE v3.0.
Southwest Oncology Group
United States: Food and Drug Administration
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