Phase II Trial of Pazopanib (GW786034) in Pre-Treated and Untreated Metastatic Melanoma Patients
I. To assess the anti-tumor activity and safety profile of single agent Pazopanib (pazopanib
I. To assess the impact of Pazopanib on circulating levels of vascular endothelial growth
II. To examine the association between tumor response and B-Raf and N-Ras mutations.
III. To examine pre/post-treatment expression levels of VEGF, vascular endothelial growth
factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and Ki67.
IV. To correlate baseline and changes in p-ERK levels in the tumor with response.
V. To determine pazopanib steady-state trough plasma concentrations (Css,min) and the
relationships between Css,min and the PD effects and toxicities of pazopanib.
VI. To examine the associations of common polymorphisms in CYP1A2, CYP2C8, UGT1A1, ABCB1,
and ABCG2 with the PK and PD of pazopanib.
VII. To Assess Progression Free Survival. VIII. To Assess Overall Survival.
OUTLINE: This is a multicenter study.
Patients receive oral pazopanib hydrochloride once daily on days 1-28. Courses repeat every
28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo tumor tissue biopsy at baseline and blood sample collection at baseline and
on days 14, 28, and 42 for research studies. Tumor tissue samples are analyzed by DNA
sequencing, ELISA, western blotting, and immunoperoxidase staining. Blood samples are
analyzed for pharmacodynamics, pharmacokinetics, and pharmacogenetics by high-performance
liquid chromatography with tandem mass spectrometry.
After completion of study treatment, patients are followed periodically for up to 5 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Tumor response rate defined as the number of eligible patients whose disease status meets the RECIST criteria for CR or PR
A ninety percent confidence interval for the true response proportion will be calculated assuming that the number of confirmed tumor responses follows a binomial distribution and using the Duffy-Santner approach.
Up to 5 years
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|