A Phase I/II Clinical and Biological Evaluation of Combined EGFR Blockade With Erlotinib and Cetuximab in Patients With Advanced Cancer (Phase I) or Advanced Colorectal Cancer (Phase II)
I. Determine the maximum tolerated dose of erlotinib hydrochloride when administered with
cetuximab in patients with advanced gastrointestinal, head and neck, or non-small cell lung
cancer. (Phase I) II. Determine the recommended phase II dose of this regimen in these
patients. (Phase I) III. Determine the response rate in patients with refractory advanced
colorectal cancer treated with this regimen. (Phase II)
I. Determine the dose-limiting toxicity of this regimen in these patients. (Phase I) II.
Determine the optimal biological dose of this regimen in these patients. (Phase I) III.
Describe any antitumor effect of this regimen in these patients. (Phase I) IV. Determine the
4-month progression-free survival rate in patients treated with this regimen. (Phase II) V.
Determine the time to tumor progression in patients treated with this regimen. (Phase II)
VI. Determine the median survival of patients treated with this regimen. (Phase II) VII.
Determine safety and tolerability of this regimen in these patients. (Phase II)
OUTLINE: This is a phase I, nonrandomized, dose-escalation study of erlotinib hydrochloride
followed by a phase II, open-label study.
PHASE I: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and oral
erlotinib hydrochloride once daily on days 8-21. Treatment repeats every 21 days in the
absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 6 patients experience dose-limiting toxicity.
PHASE II: Patients receive cetuximab and erlotinib hydrochloride as in phase I at the MTD.
After completion of study treatment, patients are followed for 4 weeks.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose and recommended phase II dose defined by dose limiting toxicities of erlotinib hydrochloride when administered with cetuximab (phase I)
United States: Food and Drug Administration
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