Temozolomide, Vincristine, and Irinotecan in Treating Young Patients With Refractory Solid Tumors
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00138216|
Recruitment Status : Completed
First Posted : August 30, 2005
Last Update Posted : February 20, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Brain and Central Nervous System Tumors Unspecified Childhood Solid Tumor, Protocol Specific||Drug: irinotecan hydrochloride Drug: temozolomide Drug: vincristine sulfate||Phase 1|
- 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.
- 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 (Clinical Trial)|
|Actual Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Temozolomide, Oral Irinotecan, and Vincristine for Children With Refractory Solid Tumors|
|Study Start Date :||October 2005|
|Actual Primary Completion Date :||June 2009|
|Actual Study Completion Date :||January 2011|
Experimental: Oral Irinotecan, temozolomide and vincristine sulfate
see detailed description
Drug: irinotecan hydrochloride
Drug: vincristine sulfate
- Determine maximum tolerated dose (MTD) of oral irinotecan [ Time Frame: 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
- To preliminarily define the antitumor activity [ Time Frame: Length of study ]To preliminarily define the antitumor activity of this drug combination within the confines of a Phase 1 study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00138216
|Study Chair:||Lars M. Wagner, MD||Children's Hospital Medical Center, Cincinnati|
|Study Chair:||John P. Perentesis, MD||Children's Hospital Medical Center, Cincinnati|