Clinical trial NCT00674193: Evaluating Dactinomycin and Vincristine in Young Patients With Cancer
Official title: A Pharmacokinetic-Pharmacodynamic-Pharmacogenetic Study of Actinomycin-D and Vincristine in Children With Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Childhood Acute Lymphoblastic Leukemia
Childhood Rhabdomyosarcoma
Childhood Soft Tissue Sarcoma
Ewing Sarcoma
Ewing Sarcoma of Bone
Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET)
Unspecified Childhood Solid Tumor, Protocol Specific
Wilms Tumor and Other Childhood Kidney Tumors
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-05-07
Enrollment: 158
Sex: ALL
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

Eligibility 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

Primary outcomes:
measure: Population PK parameters for dactinomycin and VCR
timeFrame: Not Provided
measure: Demographic and/or physiological factors that are determinants of dactinomycin and VCR disposition
timeFrame: Not Provided
Secondary outcomes:
measure: Pharmacokinetic (PK), pharmacodynamic (PD), and pharmacogenetic characteristics of dactinomycin and vincristine (VCR)
timeFrame: Not Provided
measure: Pharmacogenetic profiles of patients receiving dactinomycin and VCR
timeFrame: Not Provided
measure: Correlation between genetic variation in drug metabolizing enzymes and drug transporters and observed drug PKs and PDs in children
timeFrame: Not Provided
measure: Creation of population PK and PD models to assess the effect of drug exposure on toxicity and outcomes
timeFrame: Not Provided
measure: Correlation of dactinomycin and VCR systemic exposure metrics with toxicity outcomes
timeFrame: Not Provided
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Long Beach
country: United States
facility: Miller Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Orange
country: United States
facility: Childrens Hospital of Orange County
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center-Parnassus
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Washington, D.C.
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Nemours Children's Clinic - Jacksonville
state: Florida
city: Orlando
country: United States
facility: Nemours Childrens Clinic - Orlando
state: Florida
city: Tampa
country: United States
facility: Saint Joseph Children's Hospital of Tampa
state: Florida
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: Childrens Memorial Hospital
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Hope Children's Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Asheville
country: United States
facility: Mission Hospitals Inc
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies and Childrens Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Knoxville
country: United States
facility: East Tennessee Childrens Hospital
state: Tennessee
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Montreal
country: Canada
facility: Hospital Sainte-Justine
state: Quebec
Study officials:
affiliation: Children's Oncology Group
name: Jeffrey Skolnik
role: PRINCIPAL_INVESTIGATOR
References: