Pharmacokinetic Study of Carboplatin in Pediatric Hematopoietic Stem Cell Transplantation

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.

Study Overview

• Status: Unknown
• Conditions: Pediatric Solid Tumor
• Intervention / Treatment: Drug: Carboplatin

Detailed Description

Purpose

1. Primary objective: To evaluate the pharmacokinetics of carboplatin in pediatric HSCT patients.
2. 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.

1. Heart: a shortening fraction > 30% and ejection fraction > 45%.
2. Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal.
3. 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

1. Pregnant or nursing women.
2. Malignant or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
3. Psychiatric disorder that would preclude compliance.
4. If the clinician decides that there is a condition improper for the clinical study.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hee Young Shin, MD, PhD; Phone Number: 82-2-2072-2917; Email: hyshin@snu.ac.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Principal Investigator: HeeYeong shin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

1. Heart: a shortening fraction > 30% and ejection fraction > 45%.
2. Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal.
3. 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:

1. Pregnant or nursing women.
2. Malignant or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
3. Psychiatric disorder that would preclude compliance.
4. If the clinician decides that there is a condition improper for the clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Carboplatin-treatment arm; 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; Blood sampling will be done at the time before administration (0hr pre-dose), 1hr, 2hr, 5hr for pharmacokinetic study.; Other Names: Neoplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: The Korean Society of Pediatric Hematology Oncology
• Investigators: Principal Investigator: Hee Young Shin, MD, PhD, Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: January 2, 2015
• First Submitted That Met QC Criteria: January 12, 2015
• First Posted (Estimate): January 15, 2015

Study Record Updates

• Last Update Posted (Estimate): January 16, 2015
• Last Update Submitted That Met QC Criteria: January 15, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Carboplatin
• Other Study ID Numbers: SNUCH_carboplatinPK