Evaluating Dactinomycin and Vincristine in Young Patients With Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Childhood Solid Tumor, Protocol Specific; Ewing Sarcoma of Bone; Ewing Sarcoma; Childhood Acute Lymphoblastic Leukemia; Wilms Tumor and Other Childhood Kidney Tumors; Childhood Rhabdomyosarcoma; Childhood Soft Tissue Sarcoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET)
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study

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.

• Study Type: Observational
• Enrollment (Actual): 158

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6008
      • Princess Margaret Hospital for Children
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Hospital Sainte-Justine
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's Hospital
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Orange, California, United States, 92868-3874
      • Childrens Hospital of Orange County
    • San Diego, California, United States, 92123
      • Rady Children's Hospital - San Diego
    • San Francisco, California, United States, 94143
      • University of California San Francisco Medical Center-Parnassus
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • District of Columbia
    • Washington, D.C., District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32207-8426
      • Nemours Children's Clinic - Jacksonville
    • Orlando, Florida, United States, 32806
      • Nemours Childrens Clinic - Orlando
    • Tampa, Florida, United States, 33607
      • Saint Joseph Children's Hospital of Tampa
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60614
      • Childrens Memorial Hospital
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Hope Children's Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kosair Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • C S Mott Children's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals Inc
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Childrens Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Knoxville, Tennessee, United States, 37916
      • East Tennessee Childrens Hospital
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Texas
    • Corpus Christi, Texas, United States, 78411
      • Driscoll Children's Hospital
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • Methodist Children's Hospital of South Texas
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Midwest Children's Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with a diagnosis of cancer, including, but not limited to, any of the following: Acute lymphoblastic leukemia, Ewing sarcoma, Rhabdomyosarcoma, Soft tissue sarcoma, Wilms tumor who are due to receive or receiving dactinomycin and/or vincristine as a component of cancer treatment on another clinical trial

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Observational (pharmacological 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.

Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jeffrey Skolnik, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): June 30, 2016

Study Registration Dates

• First Submitted: May 6, 2008
• First Submitted That Met QC Criteria: May 6, 2008
• First Posted (Estimate): May 7, 2008

Study Record Updates

• Last Update Posted (Actual): May 17, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Neoplasms, Glandular and Epithelial; Genetic Diseases, Inborn; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Neoplastic Syndromes, Hereditary; Neoplasms, Complex and Mixed; Leukemia, Lymphoid; Leukemia; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Myosarcoma; Sarcoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sarcoma, Ewing; Rhabdomyosarcoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Wilms Tumor; Neuroectodermal Tumors, Primitive, Peripheral
• Other Study ID Numbers: ADVL06B1; U10CA098543 (U.S. NIH Grant/Contract); NCI-2009-00362 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); COG-ADVL06B1 (Other Identifier: Children's Oncology Group); CDR0000559243 (Other Identifier: Clinical Trials.gov)