Phase I/II Clinical, Pharmacological, and Biological Study of BAY 43-9006 in Combination With Cetuximab and Irinotecan in Patients With Advanced Colorectal Cancer
I. Determine the toxicity spectrum and dose-limiting toxic effects of sorafenib when
combined with cetuximab and irinotecan in patients with advanced or metastatic colorectal
II. Determine the recommended phase II dose of sorafenib when combined with cetuximab and
irinotecan in these patients.
III. Correlate the clinical activity of this regimen, in terms of radiologic and positron
emission tomography (PET) response, with baseline ERK expression as well as KRAS, BRAF, and
other genetic properties of tumors in these patients.
IV. Determine the pharmacokinetics of this regimen in these patients. V. Correlate the
pharmacodynamic effects of this regimen with baseline ERK expression as well as KRAS, BRAF,
and other genetic properties of tumors in these patients.
VI. Correlate the pharmacodynamic effects of this regimen on MAPK status in peripheral blood
mononuclear cells and on normal skin and oral mucosa with clinical parameters in these
OUTLINE: This is a phase I dose-escalation study of sorafenib followed by a multicenter
phase II study.
COURSE 1 (56 days): Patients receive oral sorafenib once or twice daily on days 1-56,
cetuximab IV over 1-2 hours on days 1, 8,15, 22, 29, 36, 43, and 50, and irinotecan IV over
90 minutes on days 15, 22, 29, and 36.
COURSE 2 AND ALL SUBSEQUENT COURSES (42 days): Patients receive oral sorafenib once or twice
daily on days 1-42, cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36, and
irinotecan IV over 90 minutes on days 1, 8, 15, and 22. Courses repeat every 42 days in the
absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of sorafenib 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.
PHASE II: Patients receive sorafenib at the MTD determined in phase I, cetuximab, and
irinotecan as in phase I.
After completion of study treatment, patients are followed at 30 days.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicity spectrum and dose-limiting toxicities of sorafenib in combination with cetuximab and irinotecan as assessed by NCI CTCAE v 3.0
Up to 30 days
University of Colorado at Denver Health Sciences Center
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|University of Colorado at Denver Health Sciences Center||Denver, Colorado 80045|