Evaluating Dactinomycin and Vincristine in Young Patients With Cancer
RATIONALE: Studying samples of blood and urine in the laboratory from patients with cancer may help doctors learn how dactinomycin and vincristine affect the body and how patients will respond to treatment.
PURPOSE: This laboratory study is evaluating how well dactinomycin and vincristine work in treating young patients with cancer.
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: vincristine sulfate
Genetic: polymerase chain reaction
Genetic: polymorphism analysis
Other: liquid chromatography
Other: mass spectrometry
Other: pharmacological study
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pharmacokinetic-Pharmacodynamic-Pharmacogenetic Study of Actinomycin-D and Vincristine in Children With Cancer|
- Population PK parameters for dactinomycin and VCR
- Demographic and/or physiological factors that are determinants of dactinomycin and VCR disposition
- Pharmacokinetic (PK), pharmacodynamic (PD), and pharmacogenetic characteristics of dactinomycin and vincristine (VCR)
- Pharmacogenetic profiles of patients receiving dactinomycin and VCR
- Correlation between genetic variation in drug metabolizing enzymes and drug transporters and observed drug PKs and PDs in children
- Creation of population PK and PD models to assess the effect of drug exposure on toxicity and outcomes
- Correlation of dactinomycin and VCR systemic exposure metrics with toxicity outcomes
|Study Start Date:||February 2008|
- To characterize the pharmacokinetics (PKs) of dactinomycin in infants, children, and adolescents with cancer.
- To identify demographic or physiological factors that are determinants of dactinomycin disposition.
- To characterize the PKs of vincristine (VCR) in infants, children, and adolescents with cancer.
- To identify demographic or physiological factors that are determinants of VCR disposition.
- To examine the correlation of dactinomycin and VCR systemic exposure metrics with toxicity outcomes.
- To explore the PK, pharmacodynamic, and pharmacogenetic relationships of dactinomycin and VCR in children with cancer.
OUTLINE: This is a multicenter study.
Patients undergo blood and urine collection prior to, periodically during, and after treatment with dactinomycin and vincristine for pharmacokinetic, pharmacodynamic, and pharmacogenetic analysis. Samples are analyzed using a liquid chromatography-tandem mass spectrometry assay. Genomic DNA extracted from peripheral blood mononuclear cells is isolated and analyzed by polymerase chain reaction and genotyping assays for genetic variation in genes relevant to the pharmacology of dactinomycin and vincristine.
After the final pharmacokinetic sample is collected, patients are followed for up to 6 months.