Evaluating Dactinomycin and Vincristine in Young Patients With Cancer

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00674193

Collaborator

National Cancer Institute (NCI) (NIH)

158

Enrollment

Locations

4.2

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Other: pharmacological study Other: laboratory biomarker analysis

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

To examine the correlation of dactinomycin and VCR systemic exposure metrics with toxicity outcomes.
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 Design

Study Type:

Observational

Actual Enrollment :

158 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Feb 1, 2008

Actual Primary Completion Date :

Jun 30, 2016

Arms and Interventions

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

Arm

Intervention/Treatment

Observational (pharmacological study)

Other: pharmacological study

Correlative studies

Other Names:

pharmacological studies

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 16 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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