Evaluating Dactinomycin and Vincristine in Young Patients With Cancer

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.

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