Trial Information

Phase I Study of Intravenous Irinotecan Using Selective Gastrointestinal Decontamination for Prevention of Diarrhea in Relapsed or Refractory Pediatric Solid Tumors

This is a phase I study with the exploratory investigation of at least four dosage levels
(20, 30, 45, 60) to define the tolerable dose for phase II studies. Primary consideration
will be given to determinations of the qualitative and quantitative toxicity of the
administration of irinotecan with cefpodoxime, and pharmacokinetics of irinotecan when given
with cefpodoxime.

Standard phase I escalation study in cohorts of 3-6 patients. Starting level is 20 mg/m2/d,
and subsequent levels will be 30 mg/m2/d, 45 mg/m2/d and 60 mg/m2/d. An amendment to the
study has included an intermediate level at 40 mg/m2/d.

Irinotecan will be administered as a 60-minute intravenous infusion daily for 5 consecutive
days, followed by a 2 day rest, and followed by an additional 5 consecutive days course [(qd
x 5) x 2]. Twenty-one days from the first dose will be considered one cycle of therapy.
Cefpodoxime will be given orally at 10 mg/kg/day divided BID, starting 2 days prior to the
beginning of the first course of irinotecan, and will be continued for the duration of study
participation.

Additional objectives include:

- To describe the pharmacokinetics of intravenous irinotecan when given with oral
cefpodoxime.

- To describe the dose-limiting toxicity/ies of irinotecan given on the [(qd x 5) x 2]
with oral cefpodoxime.

- To evaluate the effect of the administration of oral cefpodoxime on the amount of
intestinal beta-glucuronidase.

- To correlate the incidence and severity of diarrhea with the amount of intestinal
beta-glucuronidase.

- To describe the toxicities of irinotecan given at doses above 20 mg/m2/d

- To note tumor responses within the confines of a phase I trial