Phase I Trial of OSI-774 and CPT-11 in Patients With Advanced Solid Tumors
I. Determine the maximum tolerated dose (MTD) of erlotinib (erlotinib hydrochloride) and
irinotecan (irinotecan hydrochloride), in relation to presence or absence of UGT1A1*28
polymorphism, in patients with advanced solid tumors that overexpress epidermal growth
II. Determine the dose-limiting toxicity of these regimens in these patients. III. Determine
whether erlotinib alters the disposition of irinotecan using a previously described limited
IV. Determine factors that influence the disposition of these drugs, including genetic
variation in UGT1A1 and BCRP, in patients treated with these regimens.
V. Determine factors that influence the disposition of these drugs, in terms of tumor
BCRP-expression, in tumor samples from patients treated with these drugs at the MTD.
VI. Evaluate the effect of this regimen on epidermal growth factor receptor phosphorylation
in these patients.
VII. Assess, preliminarily, any antitumor activity in patients treated with these regimens.
VIII. Correlate, preliminarily, EGFR phosphorylation and/or BCRP -expression with response
in tumor samples from these patients.
OUTLINE: This is a dose-escalation study. Patients are stratified according to UGTA1A
genotype (all patients regardless of genotype [closed to accrual as of 9/15/04] vs UGT1A1
6/6 genotype vs UGTA1A 6/7 or 7/7 genotype).
Patients receive oral erlotinib hydrochloride daily on days -6 to -1. Patients then receive
irinotecan hydrochloride intravenously (IV) over 90 minutes on day 1 and oral erlotinib once
daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or
Cohorts of 3-6 patients per stratum receive escalating doses of erlotinib hydrochloride and
irinotecan hydrochloride until the MTD is determined. The MTD is defined as the dose
preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting
toxicity. Additional patients are treated at the MTD.
Patients are followed for 3 months.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of erlotinib hydrochloride and irinotecan hydrochloride in patients with advanced solid tumors that overexpress epidermal growth factor receptor
Defined as the highest safely tolerated dose where at most one patient experiences DLT with the next higher dose having at least 2 patients who experience DLT. Three patients will be entered at a given dose level and observed for at least 4 weeks to assess toxicity. MTD will be determined independently for each cohort.
At least 4 weeks
United States: Food and Drug Administration
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