Evaluating Dactinomycin and Vincristine in Young Patients With Cancer

Children's Oncology Group

Status: Completed

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

Treatments: Other: laboratory biomarker analysis; Other: pharmacological study

Study type: Observational

Funder types: NETWORK; NIH

Identifiers

NCT00674193

NCI-2009-00362 (Registry Identifier)

ADVL06B1

COG-ADVL06B1 (Other Identifier)

U10CA098543 (U.S. NIH Grant/Contract)

CDR0000559243 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 158 patients

Sex: All

Ages: Under 16 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

158 participants in 1 patient group

Observational (pharmacological study)

Description:

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.

Treatment:

Other: pharmacological study

Other: laboratory biomarker analysis