A Phase I Study of BAY 43-9006 (Sorafenib) in Combination With OSI-774 (Erlotinib; Tarceva) in Advanced Solid Tumors
- Determine the maximum tolerated dose and recommended phase II dose of sorafenib and
erlotinib in patients with metastatic or unresectable solid tumors.
- Determine the optimal biologically effective dose of this regimen that will lead to
hypophosphorylation of epidermal growth factor receptor (EGFR), ERK, Akt, and vascular
endothelial growth factor receptor (VEGFR), and inhibition of angiogenesis and
apoptosis with tolerable toxicity in these patients.
- Correlate the pharmacokinetic profiles of this regimen with toxicity and biological
activity in these patients.
- Determine, preliminarily, the antitumor activity of this regimen in these patients.
- Correlate phosphorylation status of EGFR, ERK, Akt, and VEGFR with antitumor activity
of this regimen in these patients.
OUTLINE: This is a multicenter, open label, non-randomized, dose-escalation study.
Patients receive oral sorafenib alone once or twice daily on days -6 to 0*. Patients then
receive oral sorafenib once or twice daily and oral erlotinib once daily on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
NOTE: *Not considered part of course 1; considered a "run-in" period only.
Cohorts of 3-6 patients receive escalating doses of sorafenib and erlotinib 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. An additional 10 patients
are treated at the MTD.
After completion of study treatment, patients are followed at 4 weeks and then at least
PROJECTED ACCRUAL: A total of 16-28 patients will be accrued for this study within 5-14
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose and recommended phase II dose
Lillian L. Siu, MD, FRCPC
Princess Margaret Hospital, Canada
United States: Federal Government