Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Evaluating Dactinomycin and Vincristine in Young Patients With Cancer

Basic Trial Information

Objectives

Primary

1. To characterize the pharmacokinetics (PKs) of dactinomycin in infants, children, and adolescents with cancer.
2. To identify demographic or physiological factors that are determinants of dactinomycin disposition.
3. To characterize the PKs of vincristine (VCR) in infants, children, and adolescents with cancer.
4. To identify demographic or physiological factors that are determinants of VCR disposition.

Secondary

1. To examine the correlation of dactinomycin and VCR systemic exposure metrics with toxicity outcomes.
2. To explore the PK, pharmacodynamic, and pharmacogenetic relationships of dactinomycin and VCR in children with cancer.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

• See Disease Characteristics
• Other concurrent chemotherapeutic agents allowed

Patient Characteristics:

• Able to comply with study requirements

Expected Enrollment

Outcomes

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

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.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Jeffrey Skolnik, MD, Protocol chair		Ph: 215-590-6359

Registry Information
Official Title		A Pharmacokinetic-Pharmacodynamic-Pharmacogenetic Study of Actinomycin-D and Vincristine in Children with Cancer
Trial Start Date		2008-02-11
Registered in ClinicalTrials.gov		NCT00674193
Date Submitted to PDQ		2007-07-05
Information Last Verified		2011-10-06
NCI Grant/Contract Number		CA98543

Back to Top