A Trial of Irinotecan and Cisplatin in Children With Refractory Solid Tumors
I. Determine the maximum tolerated dose (MTD) of irinotecan when administered with
cisplatin, with or without amifostine, to children with refractory solid tumors.
II. Determine the dose limiting toxicities of the combination of irinotecan and cisplatin,
with and without amifostine, in this patient population.
III. Determine the pharmacokinetics of cisplatin with and without amifostine in these
IV. Quantify the leukocyte DNA-platinum adduct formation, with and without amifostine, and
correlate it with response and toxicity in these patients.
V. Determine the safety and efficacy of the doses and schedules of administration to be used
in phase II clinical trials.
OUTLINE: This is a dose escalation study of irinotecan.
Treatment A: Patients receive cisplatin IV over 1 hour followed immediately by irinotecan IV
over 90 minutes on days 1, 8, 15, and 22. Courses repeat every 6 weeks. Treatment continues
for a minimum of 2 courses in the absence of unacceptable toxicity or disease progression.
Treatment B: Patients receive therapy as in treatment A. In addition, amifostine IV is
administered over 15 minutes immediately before cisplatin.
Cohorts of 3-6 patients receive escalating doses of irinotecan 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 toxicities. Once the MTD of treatment A is
determined, additional patients are accrued to determine the MTD of treatment B.
If myelosuppression is the dose limiting toxicity of treatment A, then stratum 1 closes and
stratum 2 opens and these patients with less prior therapy receive treatment A. Treatment B
is then only open to stratum 3 patients.
Patients are followed every 6 months for 4 years, then annually thereafter.
PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 2.5 years.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD defined as that dose level immediately below the dose level at which 2 patients out of 3 to 6 patients experienced dose-limiting toxicity using Common Toxicity Criteria version 2.0
Abdul Kader Souid
Swiss Pediatric Oncology Group - Geneva
United States: Food and Drug Administration