Pharmacokinetic Study of Carboplatin in Pediatric Hematopoietic Stem Cell Transplantation

Study Overview
=================
Brief Summary
-----------------
Carboplatin is widely used for conditioning regimens of autologous hematopoietic stem cell transplantation for pediatric solid tumor, but the pharmacokinetics has not been evaluated in pediatric stem cell transplantation before. As carboplatin have renal toxicity, the pharmacokinetic study of carboplatin would help the safe and effective administration of carboplatin for transplantation patients. Especially, the dose of carboplatin is higher at conditioning chemotherapy, resulting in higher toxicity. Carboplatin is a drug mostly excreted by kidney, and the dose of carboplatin is recommended according to the body surface area and kidney function, represented by glomerular filtration rate. After analyzing the pharmacokinetics of carboplatin, analyses will also be done for the methods to determine the appropriate carboplatin dose.

Detailed Description
-----------------
Purpose Primary objective: To evaluate the pharmacokinetics of carboplatin in pediatric HSCT patients. Secondary objective: To evaluate the toxicity of HSCTs using carboplatin as the conditioning regimen. To compare the pharmacokinetics of carboplatin in adults and children. Eligibility Inclusion criteria 1. Patients who undergo HSCT with conditioning regimen including carboplatin. 2. Age under 19 years. 3. Performance status: ECOG 0-2. 4. Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases. Heart: a shortening fraction > 30% and ejection fraction > 45%. Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal. Kidney: creatinine <2 × normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2. 5. Patients must lack any active viral infections or active fungal infection. 6. Patients (or one of parents if patients age < 19) should sign informed consent. Exclusion criteria Pregnant or nursing women. Malignant or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy. Psychiatric disorder that would preclude compliance. If the clinician decides that there is a condition improper for the clinical study.

Official Title
-----------------
Pharmacokinetic Study of Carboplatin in Pediatric Hematopoietic Stem Cell Transplantation

Conditions
-----------------
Pediatric Solid Tumor

Intervention / Treatment
-----------------
* Drug: Carboplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Patients who undergo HSCT with conditioning regimen including carboplatin. 2. Age under 19 years. 3. Performance status: ECOG 0-2. 4. Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases. Heart: a shortening fraction > 30% and ejection fraction > 45%. Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal. Kidney: creatinine <2 × normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2. 5. Patients must lack any active viral infections or active fungal infection. 6. Patients (or one of parents if patients age < 19) should sign informed consent. Exclusion Criteria: Pregnant or nursing women. Malignant or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy. Psychiatric disorder that would preclude compliance. If the clinician decides that there is a condition improper for the clinical study.

Ages Eligible for Study
-----------------
Maximum Age: 19 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carboplatin-treatment arm<br>Arm description : Carboplatin intravenous administration once daily for 3 to 4 days Topotecan + Thiotepa + Carboplatin : carboplatin 500mg/m2/day, for 3 days MEC for 2nd PBSCT : carboplatin 350 mg/m2/day, for 4 days MEC for other solid tumor : carboplatin 400 mg/m2/day, for 4 days MEC + MIBG Tx for 2nd PBSCT (neuroblastoma) : carboplatin 300 mg/m2/day, for 4 days | Drug: Carboplatin<br>* Blood sampling will be done at the time before administration (0hr pre-dose), 1hr, 2hr, 5hr for pharmacokinetic study.<br>* Other names: Neoplatin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under Curve (AUC) of carboplatin at the first and last administration day |  | From the start of first dose carboplatin administration to 5 hours from the last administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events after HSCT using carboplatin as the conditioning regimen | Especially, kidney function will be focused. | From the start of carboplatin administration to 100 days from hematopoietic stem cell transplantation |