A Phase I Study of Temozolomide, Oral Irinotecan, and Vincristine for Children With Refractory Solid Tumors
- 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
- Determine the pharmacokinetics of irinotecan in these patients.
- 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
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
PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 18 months.
Primary Purpose: Treatment
Lars M. Wagner, MD
Children's Hospital Medical Center, Cincinnati
United States: Federal Government
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|
|Children's Hospital of Orange County||Orange, California 92668|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Children's Memorial Hospital - Chicago||Chicago, Illinois 60614|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|SUNY Upstate Medical University Hospital||Syracuse, New York 13210|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas||Dallas, Texas 75390|
|Indiana University Melvin and Bren Simon Cancer Center||Indianapolis, Indiana 46202-5289|
|Masonic Cancer Center at University of Minnesota||Minneapolis, Minnesota 55455|
|Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center||New York, New York 10032|
|Stanford Cancer Center||Stanford, California 94305-5824|
|Lehigh Valley Hospital - Muhlenberg||Bethlehem, Pennsylvania 18017|
|Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham||Birmingham, Alabama 35294|
|Oregon Health and Science University Cancer Institute||Portland, Oregon 97239-3098|