Evaluating Dactinomycin and Vincristine in Young Patients With Cancer

Study Overview
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Brief Summary
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This laboratory study is evaluating how well dactinomycin and vincristine work in treating young patients with cancer. 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.

Detailed Description
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PRIMARY OBJECTIVES: I. To characterize the pharmacokinetics (PKs) of dactinomycin in infants, children, and adolescents with cancer. II. To identify demographic or physiological factors that are determinants of dactinomycin disposition. III. To characterize the PKs of vincristine (VCR) in infants, children, and adolescents with cancer. IV. To identify demographic or physiological factors that are determinants of VCR disposition. SECONDARY OBJECTIVES: I. To examine the correlation of dactinomycin and VCR systemic exposure metrics with toxicity outcomes. II. 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.

Official Title
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A Pharmacokinetic-Pharmacodynamic-Pharmacogenetic Study of Actinomycin-D and Vincristine in Children With Cancer

Conditions
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Childhood Acute Lymphoblastic Leukemia, Childhood Rhabdomyosarcoma, Childhood Soft Tissue Sarcoma, Ewing Sarcoma, Ewing Sarcoma of Bone, Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET), Unspecified Childhood Solid Tumor, Protocol Specific, Wilms Tumor and Other Childhood Kidney Tumors

Intervention / Treatment
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* Other: pharmacological study
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of cancer, including, but not limited to, any of the following: Acute lymphoblastic leukemia Ewing sarcoma Rhabdomyosarcoma Soft tissue sarcoma Wilms tumor Due to receive or receiving dactinomycin and/or vincristine as a component of cancer treatment on another clinical trial Able to comply with study requirements Other concurrent chemotherapeutic agents allowed

Ages Eligible for Study
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Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational (pharmacological study)<br>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. | Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Population PK parameters for dactinomycin and VCR |  | Not Provided | 
| Demographic and/or physiological factors that are determinants of dactinomycin and VCR disposition |  | Not Provided | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK), pharmacodynamic (PD), and pharmacogenetic characteristics of dactinomycin and vincristine (VCR) |  | Not Provided | 
| Pharmacogenetic profiles of patients receiving dactinomycin and VCR |  | Not Provided | 
| Correlation between genetic variation in drug metabolizing enzymes and drug transporters and observed drug PKs and PDs in children |  | Not Provided | 
| Creation of population PK and PD models to assess the effect of drug exposure on toxicity and outcomes |  | Not Provided | 
| Correlation of dactinomycin and VCR systemic exposure metrics with toxicity outcomes |  | Not Provided |