A Phase I Study Of Oral Irinotecan, Temozolomide, Cefixime In Children With Recurrent/Resistant High-Risk Neuroblastoma
- Determine the maximum tolerated dose of oral irinotecan when administered with
fixed-dose temozolomide and cefixime in pediatric patients with recurrent or resistant
- Determine the toxic effects of this regimen in these patients.
- Determine the response rate in patients treated with this regimen.
- Determine the pharmacokinetics of this regimen in these patients.
- Correlate UGT1A1 genotype with the occurrence of dose-limiting diarrhea in patients
treated with this regimen.
- Correlate BCRP genotype with pharmacokinetic phenotype in patients treated with this
- Correlate p53 status in tumor cells with response in patients treated with this
OUTLINE: This is a multicenter, dose-escalation study of irinotecan.
Patients receive oral cefixime once daily beginning 5 days before the start of fixed-dose
temozolomide and irinotecan and continuing for the duration of the study. Patients also
receive oral temozolomide once daily on days 1-5 and oral irinotecan once daily on days 1-5
and 8-12. Courses repeat every 21 days in the absence of disease progression or unacceptable
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 toxicity. A maximum of 12 patients are treated at the
Patients are followed for toxicity, response, and survival.
PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 1.25
Primary Purpose: Treatment
Lars M. Wagner, MD
Children's Hospital Medical Center, Cincinnati
United States: Food and Drug Administration
|University of Michigan Comprehensive Cancer Center||Ann Arbor, Michigan 48109-0752|
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Indiana University Cancer Center||Indianapolis, Indiana 46202-5265|
|Children's Hospital Los Angeles||Los Angeles, California 90027-0700|
|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|
|UCSF Comprehensive Cancer Center||San Francisco, California 94115|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Lucile Packard Children's Hospital at Stanford University Medical Center||Palo Alto, California 95798|
|AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus||Atlanta, Georgia 30322|
|Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital||Houston, Texas 77030-2399|
|Children's Hospital Boston||Boston, Massachusetts 02115|