A Phase I Study of Temozolomide, Oral Irinotecan, and Vincristine for Children With Refractory Solid Tumors

Brief Summary

Detailed Description

OBJECTIVES: Primary * Determine the maximum tolerated dose and recommended phase II dose of irinotecan when administered with temozolomide and vincristine in young patients with refractory solid tumors, including brain tumors. * Determine the toxic effects of this regimen in these patients. * Compare the toxic effects of this regimen in patients with low- vs high-risk UGT1A1 genotypes. * Determine the pharmacokinetics of irinotecan in these patients. Secondary * Determine, preliminarily, the antitumor activity of this regimen in these patients. * Correlate UGT1A1, UGT1A7, UGT1A9, and BCRP genotypes with the pharmacokinetics and pharmacodynamics of irinotecan and its metabolites in these patients. OUTLINE: This is a multicenter, dose-escalation study of irinotecan. Patients are stratified according to UGT1A1 genotype (high-risk \[7/7 or 6/7 genotype AND bilirubin ≥ 0.6 mg/dL\] vs low-risk \[absence of high-risk criteria\]) if a high-risk patient experiences a dose-limiting toxicity (DLT). Patients receive oral temozolomide on days 1-5 and oral irinotecan on days 1-5 and 8-12. Patients also receive vincristine IV over 1 minute on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity. 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 6 patients experience DLT. After completion of study treatment, patients are followed for 1 month and then annually thereafter. PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 18 months.

Primary Outcomes

Secondary Outcomes

• To preliminarily define the antitumor activity(Length of study)