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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham, Alabama, United States
Children's Hospital of Orange County
Orange, California, United States
Stanford Cancer Center
Stanford, California, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, United States
SUNY Upstate Medical University Hospital
Syracuse, New York, United States
...and 8 more locations
Determine maximum tolerated dose (MTD) of oral irinotecan
To estimate the maximum tolerated dose (MTD) of oral irinotecan administered on two different schedules together with fixed-dose temozolomide and vincristine in children with refractory solid tumors or brain tumors
Time frame: length of study
To preliminarily define the antitumor activity
To preliminarily define the antitumor activity of this drug combination within the confines of a Phase 1 study.
Time frame: Length of study
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.