A Phase I Study of Oxaliplatin, 5-Fluorouracil, and Leucovorin in Combination With Oral Capecitabine in Patients With Advanced Malignancy
I. To establish the MTD and toxicity profile of oral capecitabine in combination with q 2
weekly intravenous oxaliplatin in patients with advanced malignancies.
I. To characterize the pharmacokinetic parameters of capecitabine at the recommended phase
II dose for combinations of capecitabine, oxaliplatin, 5-fluorouracil, and leucovorin, as
well as for the combination of capecitabine and oxaliplatin.
II. To observe for and record any antitumor activity.
OUTLINE: This is a dose-escalation study of capecitabine.
Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil IV on
days 1 and 15. Patients also receive oral capecitabine every 8 hours on days 1-2 and 15-16.
Leucovorin calcium and fluorouracil administration is held at dose level 4 and above.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated
dose (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. Once the MTD is determined, at
least 6 additional patients are accrued to receive treatment at the recommended phase II
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD, defined as the highest dose level which results in DLT in fewer than 2/6 patients, graded according to the NCI CTC version 2.0
Up to 28 days
University of Wisconsin Hospital and Clinics
United States: Food and Drug Administration
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