Unspecified Childhood Solid Tumor, Protocol Specific
Conditions
Keywords
unspecified childhood solid tumor, protocol specific
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.
Interventions
OTHERpharmacological study
pharmacological studies
PROCEDUREdual x-ray absorptimetry
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Population Estimates for Daunorubicin Hydrochloride Clearance | 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. | 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. |
| Population Estimates for Daunorubicin Hydrochloride Volume of Distribution | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relationship Between Pharmacokinetics and Toxicity | Length of Study | Mean (standard deviation) of daunorubicin hydrochloride clearance will be summarized for occurrence of various toxicities |
| Relationship Between Body Composition and the Pharmacokinetics of Daunorubicin Hydrochloride | Length of study | Mean (standard deviation) of daunorubicin hydrochloride clearance will be summarized by Body composition (\<30% versus \>=30%) |
| Relationship Between Pharmacokinetics, and Genetic Polymorphisms | Length of Study | Mean (standard deviation) of daunorubicin hydrochloride clearance will be summarized by genotype |
| Relationship Between Pharmacokinetics, Renal and Hepatic Function, and Complete Blood Count | Length of Study | Mean (standard deviation) of daunorubicin hydrochloride clearance will be summarized by organ function/baseline laboratory values |
| Correlation of the Pharmacokinetics of Daunorubicin Hydrochloride With Gender, Age, or Ethnic Background | Length of Study | 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) |
Countries
Australia, Canada, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 107 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Unable to obtain specimen | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Pharmacokinetics of Daunorubicin Chemotherapy Patients |
|---|---|
| Age, Categorical <=18 years | 99 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 11.5 years STANDARD_DEVIATION 5.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 82 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) White | 82 Participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 50 / 107 |
| serious Total, serious adverse events | 0 / 107 |
Outcome results
Primary
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.
Time frame: 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: There were 107 patients enrolled, 4 participants withdrew consent and there was 1 patient with insufficient specimen. 4 other participants were not analyzed as all sample time points were required for analysis and were not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pharmacokinetics of Daunorubicin Chemotherapy Patients | Population Estimates for Daunorubicin Hydrochloride Clearance | 116 L/m2/hr | Standard Deviation 14 |
Primary
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.
Time frame: 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: There were 107 patients enrolled, 4 participants withdrew consent and there was 1 participant with insufficient specimen. 4 other participants were not analyzed as all samples time points were required for analysis and were not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pharmacokinetics of Daunorubicin Chemotherapy Patients | Population Estimates for Daunorubicin Hydrochloride Volume of Distribution | 68.1 Liter | Standard Deviation 24 |
Secondary
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)
Time frame: Length of Study
Secondary
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%)
Time frame: Length of study
Secondary
Relationship Between Pharmacokinetics, and Genetic Polymorphisms
Mean (standard deviation) of daunorubicin hydrochloride clearance will be summarized by genotype
Time frame: Length of Study
Secondary
Relationship Between Pharmacokinetics and Toxicity
Mean (standard deviation) of daunorubicin hydrochloride clearance will be summarized for occurrence of various toxicities
Time frame: Length of Study
Secondary
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
Time frame: Length of Study