Phase II Study of Bevacizumab Plus Erlotinib in Patients With Advanced Hepatocellular Cancer (HCC)
I. Evaluate the objective response rate in patients with advanced hepatocellular carcinoma
treated with bevacizumab and erlotinib.
I. Evaluate the time to progression in patients treated with this regimen. II. Evaluate the
overall and progression-free survival of patients treated with this regimen.
III. Evaluate the adverse events in patients treated with this regimen.
I. Determine the presence of epidermal growth factor receptor (EGFR) mutations in tumor
tissue and correlate this with response rate, progression, and survival in patients treated
with this regimen.
II. Evaluate the expression of molecules involved in EGFR signal transduction, including
EGFR, phosphorylated-EGFR, Akt, phosphorylated-Akt, mitogen-activated protein kinase (MAPK),
phosphorylated-MAPK, and HER2/neu by immunohistochemistry (from tumor tissue) and correlate
these with patient outcome measures.
III. Determine the levels of vascular endothelial growth factor (VEGF) and VEGF receptors in
tumor tissue as well as baseline plasma VEGF levels and correlate these with patient outcome
OUTLINE: This is a multicenter study.
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib
hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of
disease progression or unacceptable toxicity. Patients undergo laboratory studies to
determine epidermal growth factor receptor (EGFR) and phosphorylated-EGFR protein levels
using initial diagnostic biopsy specimens by immunohistochemistry (IHC) for correlation with
clinical outcome. Levels of proteins through which EGFR signals, including Akt,
phosphorylated-Akt, mitogen-activated protein kinase (MAPK), and phosphorylated-MAPK, are
also determined using initial diagnostic biopsy specimens by IHC and correlated with
clinical outcome. Total and free serum vascular endothelial growth factor levels are
determined at the start of study and prior to course 3 by enzyme-linked immunosorbent assays
After completion of study treatment, patients are followed periodically for up to 3 years.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of confirmed tumor responses defined to be either a CR or PR
Estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. The largest success proportion where the proposed treatment regimen would be considered ineffective in this population is 10%, and the smallest proportion that would warrant subsequent studies with the proposed regimen in this patient population is 25%.
Assessed up to 3 years
United States: Food and Drug Administration
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