Pharmacokinetics of Daunorubicin in Young Patients With Cancer

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Pharmacokinetics of Daunomycin in Children

Conditions
-----------------
Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
-----------------
* Other: pharmacological study
* Procedure: dual x-ray absorptimetry


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pharmacokinetics of Daunorubicin chemotherapy patients<br>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<br>* pharmacological studies<br>Procedure: dual x-ray absorptimetry<br> <br> * Other names: 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
unspecified childhood solid tumor, protocol specific