Temozolomide, Vincristine, and Irinotecan in Treating Young Patients With Refractory Solid Tumors
- Conditions
- Brain and Central Nervous System TumorsUnspecified Childhood Solid Tumor, Protocol Specific
- Interventions
- Registration Number
- NCT00138216
- Lead Sponsor
- Children's Oncology Group
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Oral Irinotecan, temozolomide and vincristine sulfate vincristine sulfate see detailed description Oral Irinotecan, temozolomide and vincristine sulfate irinotecan hydrochloride see detailed description Oral Irinotecan, temozolomide and vincristine sulfate temozolomide see detailed description
- Primary Outcome Measures
Name Time Method Determine maximum tolerated dose (MTD) of oral irinotecan length of study 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
- Secondary Outcome Measures
Name Time Method To preliminarily define the antitumor activity Length of study To preliminarily define the antitumor activity of this drug combination within the confines of a Phase 1 study.
Trial Locations
- Locations (18)
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
🇺🇸New York, New York, United States
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
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
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
🇺🇸Birmingham, Alabama, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Oregon Health and Science University Cancer Institute
🇺🇸Portland, Oregon, United States
Children's Memorial Hospital - Chicago
🇺🇸Chicago, Illinois, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States