A Phase I And Pharmacogenetic Study Of CPT-11, Oxaliplatin, And Capecitabine In Patients With Solid Tumors
I. To define the maximally tolerated dose of the combination of CPT-11 (irinotecan
hydrochloride), oxaliplatin, and capecitabine in three different populations, based on UDP
glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) genotype (6/6, 6/7, and 7/7).
II. To identify any activity of this treatment combination in patients with metastatic
III. To examine the differences in the toxicity profile, especially pertaining to
hematologic and gastrointestinal (GI), and the maximally tolerated dose of the combination
of CPT-11, oxaliplatin and capecitabine with respect to the UGT1A1 haplotypes.
IV. Examine the effect of the UGT1A1 genotype on the pharmacokinetics of CPT-11 and its
OUTLINE: This is a dose-escalation study. Patients are stratified according to UGT1A1
genotype (6/6 vs 6/7 [closed to accrual as of 8/24/06] vs 7/7).
Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes and oxaliplatin
IV over 2 hours on day 1 and capecitabine orally (PO) twice daily (QD) on days 2-15. Courses
repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride, oxaliplatin,
and capecitabine 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. Once the MTD is determined, an additional 6-10 patients (for a total of 12
patients) receive treatment at that dose.
After completion of study treatment, patients are followed up at 3 months.
PROJECTED ACCRUAL: A total of 54-84 patients (12-22 for stratum I, 18-28 for stratum II
[closed to accrual as of 8/24/06], and 24-34 for stratum III) will be accrued for this study
within approximately 4.4 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD defined as one dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) assessed using NCI CTCAE v3.0
United States: Food and Drug Administration
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