Evaluating Dactinomycin and Vincristine in Young Patients With Cancer

Condition(s) targeted: Kidney Cancer; Leukemia; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Intervention: dactinomycin (Drug); vincristine sulfate (Drug); liquid chromatography (Procedure); mass spectrometry (Procedure); pharmacological study (Procedure); polymerase chain reaction (Procedure); polymorphism analysis (Procedure)

Phase: N/A

Status: Recruiting

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Jeffrey M. Skolnik, MD, Study Chair, Affiliation: Children's Hospital of Philadelphia

RATIONALE: 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.

PURPOSE: This laboratory study is evaluating how well dactinomycin and vincristine work in treating young patients with cancer.

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

Study design: Treatment, Open Label

Primary outcome:

Population PK parameters for dactinomycin and VCR

Demographic and/or physiological factors that are determinants of dactinomycin and VCR disposition

Secondary outcome:

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

Detailed description: OBJECTIVES:

Primary

- 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

- 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.

Minimum age: N/A. Maximum age: 16 Years. Gender(s): Both.

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

PATIENT CHARACTERISTICS:

- Able to comply with study requirements

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Other concurrent chemotherapeutic agents allowed

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham, Birmingham, Alabama 35294, United States; Recruiting
Clinical Trials Office - Lurleen Wallace Comprehensive Cancer, Phone: 205-934-0309

Children's Hospital of Orange County, Orange, California 92868, United States; Recruiting
Violet Shen, Phone: 714-532-8636

Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California 90095-1781, United States; Recruiting
Clinical Trials Office - Jonsson Comprehensive Cancer Center a, Phone: 888-798-0719

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94115, United States; Recruiting
Clinical Trials Office - UCSF Helen Diller Family Comprehensi, Phone: 877-827-3222

Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803, United States; Recruiting
Clinical Trials Office - Alfred I. duPont Hospital for Childre, Phone: 302-651-5755

Children's National Medical Center, Washington, District of Columbia 20010-2970, United States; Recruiting
Clinical Trials Office - Children's National Medical Center, Phone: 202-884-2549

Nemours Children's Clinic, Jacksonville, Florida 32207, United States; Recruiting
Eric Sandler, Phone: 904-390-3793

Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, United States; Recruiting
Howard M. Katzenstein, Phone: 404-785-0853

Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States; Recruiting
David O. Walterhouse, Phone: 773-755-6514

Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202-5289, United States; Recruiting
Clinical Trials Office - Indiana University Cancer Center, Phone: 317-274-2552

St. Vincent Indianapolis Hospital, Indianapolis, Indiana 46260, United States; Recruiting
Clinical Trials Office - St. Vincent Indianapolis Hospital, Phone: 317-338-2194

Kosair Children's Hospital, Louisville, Kentucky 40232, United States; Recruiting
Clinical Trials Office - Kosair Children's Hospital, Phone: 502-629-5500, Email: CancerResource@nortonhealthcare.org

Lucille P. Markey Cancer Center at University of Kentucky, Lexington, Kentucky 40536-0093, United States; Recruiting
Clinical Trials Office - Markey Cancer Center at University of, Phone: 859-257-3379

C.S. Mott Children's Hospital at University of Michigan Medical Center, Ann Arbor, Michigan 48109-0286, United States; Recruiting
Clinical Trials Office - C.S. Mott Children's Hospital, Phone: 800-865-1125

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States; Recruiting
Clinical Trials Office - All Mayo Clinic Locations, Phone: 507-538-7623

University of Mississippi Cancer Clinic, Jackson, Mississippi 39216-4505, United States; Recruiting
Gail C. Megason, Phone: 601-984-5220

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis, St. Louis, Missouri 63110, United States; Recruiting
Robert J. Hayashi, Phone: 314-454-4118

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, New York, New York 10032, United States; Recruiting
Clinical Trials Office - Herbert Irving Comprehensive Cancer C, Phone: 212-305-8615

Mission Hospitals - Memorial Campus, Asheville, North Carolina 28801, United States; Recruiting
Clinical Trials Office - Mission Hospitals - Memorial Campus, Phone: 828-213-4150

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States; Recruiting
Clinical Trials Office - Cincinnati Children's Hospital Medica, Phone: 513-636-0161

Oklahoma University Cancer Institute, Oklahoma City, Oklahoma 73104, United States; Recruiting
Rene Y. McNall-Knapp, Phone: 405-271-5311

Oregon Health and Science University Cancer Institute, Portland, Oregon 97239-3098, United States; Recruiting
Clinical Trials Office - Oregon Health and Science University, Phone: 503-494-1080, Email: trials@ohsu.edu

Hollings Cancer Center at Medical University of South Carolina, Charleston, South Carolina 29425, United States; Recruiting
Clinical Trials Office - Hollings Cancer Center at Medical Uni, Phone: 843-792-9321

St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States; Recruiting
Clinical Trials Office - St. Jude Children's Research Hospital, Phone: 901-495-4644

Baylor University Medical Center - Houston, Houston, Texas 77030-2399, United States; Recruiting
Alberto Pappo, Phone: 832-822-4248

CCOP - Scott and White Hospital, Temple, Texas 76508, United States; Recruiting
Arlynn F. Mulne, Phone: 254-724-2006

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas, Texas 75390, United States; Recruiting
Clinical Trials Office - Simmons Comprehensive Cancer Center a, Phone: 866-460-4673; 214-648-7097

Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia; Recruiting
Catherine Cole, Phone: 011-6189340-8238

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: February 2008
Last updated: October 14, 2008