Pharmacokinetics of Daunorubicin in Young Patients With Cancer

Pharmacokinetics of Daunomycin in Children

This laboratory study is looking at the pharmacokinetics of daunorubicin in young patients with cancer. Collecting and storing samples of blood from patients with cancer to study in the laboratory may help doctors learn more about how patients respond to treatment with certain chemotherapy drugs.

Study Overview

• Status: Completed
• Conditions: Unspecified Childhood Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: pharmacological study; Procedure: dual x-ray absorptimetry

Detailed Description

OBJECTIVES:

Primary

• Determine the pharmacokinetics of daunorubicin hydrochloride in pediatric patients with malignancy.

Secondary

• Evaluate the relationship between body composition (percent body fat) and the pharmacokinetics of daunorubicin hydrochloride in these patients.
• Correlate the pharmacokinetics of daunorubicin hydrochloride with gender, age, or ethnic background in these patients.
• Explore, in a preliminary fashion, possible relationships between pharmacokinetic results and toxicity.
• Explore, in a preliminary fashion, possible relationships between pharmacokinetic results and renal and hepatic function and complete blood count.
• Explore, in a preliminary fashion, possible genetic polymorphisms that may influence daunorubicin hydrochloride disposition.

OUTLINE: This is a multicenter study.

Patients undergo blood collection prior to, periodically during, and after treatment with daunorubicin hydrochloride for pharmacokinetic analysis.

Patients also undergo body composition testing within 7 days before or after the administration of daunorubicin hydrochloride using dual-energy x-ray absorptiometry.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6001
      • Princess Margaret Hospital for Children
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Hopital Sainte Justine
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre at the University of Saskatchewan
• Switzerland
  • Bern, Switzerland, 3010
    • Swiss Pediatric Oncology Group Bern
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB Comprehensive Cancer Center
  • Arizona
    • Phoenix, Arizona, United States, 85016-7710
      • Phoenix Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Childrens Hospital Los Angeles
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
    • Stanford, California, United States, 94305-5824
      • Stanford Cancer Center
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I. DuPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2970
      • Children's National Medical Center
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Lee Cancer Care of Lee Memorial Health System
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Pensacola, Florida, United States, 32504
      • Sacred Heart Cancer Center at Sacred Heart Hospital
    • Saint Petersburg, Florida, United States, 33701
      • All Children's Hospital
    • Tampa, Florida, United States, 33607
      • St. Joseph's Cancer Institute at St. Joseph's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
    • Augusta, Georgia, United States, 30912-3730
      • MBCCOP - Medical College of Georgia Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital - Chicago
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Melvin and Bren Simon Cancer Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille P. Markey Cancer Center at University of Kentucky
    • Louisville, Kentucky, United States, 40232
      • Kosair Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0286
      • C.S. Mott Children's Hospital at University of Michigan Medical Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota - Minneapolis
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center at University of Minnesota
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Cancer Clinic
  • Missouri
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center at University of Missouri - Columbia
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • Nevada
    • Las Vegas, Nevada, United States, 89109-2306
      • CCOP - Nevada Cancer Research Foundation
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center Cancer Center
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Center
  • New York
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals - Memorial Campus
  • Ohio
    • Akron, Ohio, United States, 44308-1062
      • Akron Children's Hospital
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43205-2696
      • Nationwide Children's Hospital
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Knight Cancer Institute At Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-9786
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
  • Tennessee
    • Knoxville, Tennessee, United States, 37901
      • East Tennessee Children's Hospital
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Corpus Christi, Texas, United States, 78411
      • Driscoll Children's Hospital
    • Dallas, Texas, United States, 75390
      • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center - Fort Worth
    • Houston, Texas, United States, 77030-4009
      • M. D. Anderson Cancer Center at University of Texas
    • Houston, Texas, United States, 77030-2399
      • Baylor University Medical Center - Houston
    • San Antonio, Texas, United States, 78207
      • University of Texas Health Science Center at San Antonio
  • Washington
    • Seattle, Washington, United States, 98105
      • Children's Hospital and Regional Medical Center - Seattle
    • Spokane, Washington, United States, 99220-2555
      • Providence Cancer Center at Sacred Heart Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Midwest Children's Cancer Center at Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of any malignancy
• Must be receiving a chemotherapy regimen that includes daunorubicin hydrochloride administered as an infusion of any duration for < 24 hours on either a 1- or a 2-day schedule, including bolus and all short infusion schedules

PATIENT CHARACTERISTICS:

• Not pregnant or nursing
• No significant uncontrolled systemic illness
• Large implanted prostheses allowed (should not undergo dual energy x-ray absorptiometry scan)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pharmacokinetics of Daunorubicin chemotherapy patients; Patients receiving a chemotherapy regimen including daunorubicin hydrochloride administered as an infusion of any duration < 24 hours on a 1 or a 2 day schedule. Pre-study evaluations no greater than 14 days prior to daunomycin administration. If patients have had significant intercurrent illness or treatment that might affect organ function, laboratory work should be performed at an appropriately closer interval to daunomycin administration. A complete history and physical examination including height, weight and body surface area. Patients should be weighed with only light clothing; shoes must be removed before weight is measured. Patients height should be measured using a stadiometer after removing shoes. Laboratory evaluation: a) CBC with differential and platelet count. b) ALT, AST, bilirubin, creatinine, total protein, albumin, alkaline phosphatase, GGT.

Other: pharmacological study; pharmacological studies; Procedure: dual x-ray absorptimetry; Other Names: DEXA scan; dual energy x-ray absorptimetry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Population Estimates for Daunorubicin Hydrochloride Clearance	Pharmacokinetic parameters of Daunorubicin hydrochloride will be analyzed, samples were drawn according to the following schedule: prior to the drug infusion, at the midpoint of the infusion if infusion is ≥ 30 min in duration, end of infusion and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 (when feasible) hours after the end of the infusion. Samples will also be collected at 24, 48, and 72 (when feasible) hours after the end of the infusion. The concentration time data will be analyzed by model dependent and model-independent means. Pharmacokinetic data will be analyzed using ADAPT II software (Biomedical Simulations Resource, University of Southern California). Mean Daunorubicin hydrochloride Clearance will be assessed.	Prior to drug infusion, midpoint, and end of infusion. Also 0.5,1,1.5,2,3,4,6,8 and 12 hours after end of infusion.
Population Estimates for Daunorubicin Hydrochloride Volume of Distribution	Pharmacokinetic parameters of Daunorubicin hydrochloride will be analyzed, samples were drawn according to the following schedule: prior to the drug infusion, at the midpoint of the infusion if infusion is ≥ 30 min in duration, end of infusion and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 (when feasible) hours after the end of the infusion. Samples will also be collected at 24, 48, and 72 (when feasible) hours after the end of the infusion. The concentration time data will be analyzed by model dependent and model-independent means. Pharmacokinetic data will be analyzed using ADAPT II software (Biomedical Simulations Resource, University of Southern California). Mean volume of distribution will be assessed.	Prior to drug infusion, midpoint, and end of infusion. Also 0.5,1,1.5,2,3,4,6,8 and 12 hours after end of infusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship Between Body Composition and the Pharmacokinetics of Daunorubicin Hydrochloride	Mean (standard deviation) of daunorubicin hydrochloride clearance will be summarized by Body composition (<30% versus >=30%)	Length of study
Correlation of the Pharmacokinetics of Daunorubicin Hydrochloride With Gender, Age, or Ethnic Background	Mean (standard deviation) of daunorubicin hydrochloride clearance will be summarized by Gender (Male versus Female), Age group (<median age versus >=median age in years), Race (White vs. Black vs. Other)	Length of Study
Relationship Between Pharmacokinetics and Toxicity	Mean (standard deviation) of daunorubicin hydrochloride clearance will be summarized for occurrence of various toxicities	Length of Study
Relationship Between Pharmacokinetics, Renal and Hepatic Function, and Complete Blood Count	Mean (standard deviation) of daunorubicin hydrochloride clearance will be summarized by organ function/baseline laboratory values	Length of Study
Relationship Between Pharmacokinetics, and Genetic Polymorphisms	Mean (standard deviation) of daunorubicin hydrochloride clearance will be summarized by genotype	Length of Study

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Stacey L. Berg, MD, Texas Children's Cancer Center

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): March 31, 2020

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): April 14, 2020
• Last Update Submitted That Met QC Criteria: April 6, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: unspecified childhood solid tumor, protocol specific
• Other Study ID Numbers: ABTR06C1; CDR0000490024 (Other Identifier: Clinical Trials.gov); COG-ABTR06C1 (Other Identifier: Children's Oncology Group); NCI-2009-00327 (Other Identifier: Registry ID: CTRP (Clinical Trial Reporting Program))