NCT00138216

Temozolomide, Vincristine, and Irinotecan in Treating Young Patients With Refractory Solid Tumors

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 42 (actual)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, vincristine, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when given together with temozolomide and vincristine in treating young patients with refractory solid tumors.

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.

Conditions

• Brain and Central Nervous System Tumors
• Unspecified Childhood Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	irinotecan hydrochloride
DRUG	temozolomide
DRUG	vincristine sulfate

Timeline

• Start date: 2005-10-01
• Primary completion: 2009-06-01
• Completion: 2011-01-01
• First posted: 2005-08-30
• Last updated: 2023-10-02

Locations

18 sites across 2 countries: United States, Canada