A Phase 2 Study of AZD6244 in Advanced or Metastatic Hepatocellular Carcinoma
- To ascertain the objective response rate (complete response and partial response) in
patients with locally advanced or metastatic hepatocellular carcinoma treated with
- To assess the safety and tolerability of AZD6244 when administered to patients with
hepatocellular carcinoma and mild (Child's A to compensated Child's B) liver
- To describe the pharmacokinetics (PK) of AZD6244 in this patient population and compare
in exploratory fashion to the established PK profile in patients with normal hepatic
- To estimate the time to event functions of progression, progression-free survival
(PFS), (and PFS associated with treatment), and overall survival.
- To explore, preliminarily, the possible correlations between baseline mitogen-activated
protein kinase (MEK) activation (i.e., presence of phospho-MEK) and radiographic
response or time to progression.
- To investigate the effects of AZD6244 on MEK kinase activity in peripheral blood
mononuclear cells from patients treated with this drug.
OUTLINE: This is a multicenter study.
Patients receive a single dose of AZD6244 on day 1 and undergo blood collection for
pharmacokinetic (PK) sampling pre-dose (within 30 min of dosing), 15 and 30 minutes and 1,
2, 4, 8, 12, 24 and 48 hours post-dose. Beginning 48 hours after the initial dose and
continuing until day 21, patients receive oral AZD6244 twice daily. Patients also undergo
blood collection for PK sampling on day 15 of course 1. In all subsequent courses, patients
receive AZD6244 on days 1-21. Treatment repeats every 21 days in the absence of disease
progression or unacceptable toxicity.
AZD6244 blood concentrations are quantified by high performance liquid chromatography.
Patients also undergo tumor biopsy by CT or ultrasound guidance at baseline and on day 8.
Peripheral blood mononuclear cells and tumor tissue are evaluated for mitogen-activated
protein kinase baseline activity and post-treatment activity.
After completion of study treatment, patients are followed periodically for up to 2 years.
Masking: Open Label, Primary Purpose: Treatment
Objective response rate
Bert H. O'Neil, MD
UNC Lineberger Comprehensive Cancer Center
United States: Food and Drug Administration
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill||Chapel Hill, North Carolina 27599-7570|
|Winship Cancer Institute of Emory University||Atlanta, Georgia 30322|
|Virginia Commonwealth University Massey Cancer Center||Richmond, Virginia 23298-0037|
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida||Tampa, Florida 33612|