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Evaluating Dactinomycin and Vincristine in Young Patients With Cancer

Completed
Conditions
Ewing Sarcoma of Bone
Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET)
Unspecified Childhood Solid Tumor, Protocol Specific
Childhood Acute Lymphoblastic Leukemia
Childhood Soft Tissue Sarcoma
Childhood Rhabdomyosarcoma
Ewing Sarcoma
Wilms Tumor and Other Childhood Kidney Tumors
Interventions
Other: pharmacological study
Other: laboratory biomarker analysis
Registration Number
NCT00674193
Lead Sponsor
Children's Oncology Group
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
158
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

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Observational (pharmacological study)laboratory biomarker analysisPatients 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.
Observational (pharmacological study)pharmacological studyPatients 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.
Primary Outcome Measures
NameTimeMethod
Population PK parameters for dactinomycin and VCRNot Provided
Demographic and/or physiological factors that are determinants of dactinomycin and VCR dispositionNot Provided
Secondary Outcome Measures
NameTimeMethod
Pharmacogenetic profiles of patients receiving dactinomycin and VCRNot Provided
Correlation between genetic variation in drug metabolizing enzymes and drug transporters and observed drug PKs and PDs in childrenNot Provided
Correlation of dactinomycin and VCR systemic exposure metrics with toxicity outcomesNot Provided
Pharmacokinetic (PK), pharmacodynamic (PD), and pharmacogenetic characteristics of dactinomycin and vincristine (VCR)Not Provided
Creation of population PK and PD models to assess the effect of drug exposure on toxicity and outcomesNot Provided

Trial Locations

Locations (38)

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Rainbow Babies and Childrens Hospital

🇺🇸

Cleveland, Ohio, United States

Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

Driscoll Children's Hospital

🇺🇸

Corpus Christi, Texas, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

Rady Children's Hospital - San Diego

🇺🇸

San Diego, California, United States

Miller Children's Hospital

🇺🇸

Long Beach, California, United States

Nemours Children's Clinic - Jacksonville

🇺🇸

Jacksonville, Florida, United States

Children's National Medical Center

🇺🇸

Washington, D.C., District of Columbia, United States

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Indiana University Medical Center

🇺🇸

Indianapolis, Indiana, United States

Childrens Hospital of Orange County

🇺🇸

Orange, California, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Connecticut Children's Medical Center

🇺🇸

Hartford, Connecticut, United States

Hospital Sainte-Justine

🇨🇦

Montreal, Quebec, Canada

University of Illinois

🇺🇸

Chicago, Illinois, United States

St. Jude Children's Research Hospital

🇺🇸

Memphis, Tennessee, United States

Advocate Hope Children's Hospital

🇺🇸

Oak Lawn, Illinois, United States

East Tennessee Childrens Hospital

🇺🇸

Knoxville, Tennessee, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

Princess Margaret Hospital for Children

🇦🇺

Perth, Western Australia, Australia

Mission Hospitals Inc

🇺🇸

Asheville, North Carolina, United States

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Childrens Memorial Hospital

🇺🇸

Chicago, Illinois, United States

Children's Hospital of Pittsburgh of UPMC

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

University of California San Francisco Medical Center-Parnassus

🇺🇸

San Francisco, California, United States

Methodist Children's Hospital of South Texas

🇺🇸

San Antonio, Texas, United States

Midwest Children's Cancer Center

🇺🇸

Milwaukee, Wisconsin, United States

Nemours Childrens Clinic - Orlando

🇺🇸

Orlando, Florida, United States

Saint Joseph Children's Hospital of Tampa

🇺🇸

Tampa, Florida, United States

Kosair Children's Hospital

🇺🇸

Louisville, Kentucky, United States

C S Mott Children's Hospital

🇺🇸

Ann Arbor, Michigan, United States

Wake Forest University Health Sciences

🇺🇸

Winston-Salem, North Carolina, United States

Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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