Pharmacokinetics of Ch14.18 in Younger Patients With High-Risk Neuroblastoma

Pain Clinical Trial

Official title:

Pharmacokinetics of the Chimeric Anti-GD2 Antibody, ch14.18, in Children With High-Risk Neuroblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01418495
• Other study ID #: NCI-2011-02975
• Secondary ID: NCI-2011-02975CH
• Status: Completed
• Start date: May 26, 2011

Study information

• Verified date: September 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This research trial is studying how Ch14.18 acts in the body of younger patients with high-risk neuroblastoma. Studying samples of blood from patients with cancer receiving Ch14.18 may help doctors learn more about how this drug is used by the body to develop better ways to give the drug to potentially improve its effectiveness and lessen its side effects.

Description:

PRIMARY OBJECTIVES:

I. Describe the pharmacokinetics of ch14.18 (monoclonal antibody Ch14.18) in children with high-risk neuroblastoma.

II. Quantify the degree of inter-patient and intra-patient variability in the clearance of ch14.18, and correlate ch14.18 clearance with patient characteristics, the presence of human anti-chimeric antibody (HACA), tumor burden (assessed on scans), and plasma GD2 levels to identify sources of variability in the clearance.

III. Develop a pharmacokinetic model to describe the pharmacokinetic profile of ch14.18 and derive pharmacokinetic (PK) parameters.

SECONDARY OBJECTIVES:

I. Correlate plasma concentrations of ch14.18 with the severity of neuropathic pain, which is being quantified using an observational pain scale, and the total dose of morphine administered to control pain.

II. Develop a limited sampling strategy that will accurately quantify the area under the curve (AUC) of ch14.18.

III. Simulate alternative dosing strategies with the pharmacokinetic model in order to reduce variability and simplify drug administration.

OUTLINE:

Patients undergo blood sample collection at baseline and during and after course 1, 3, or 5 of treatment for pharmacokinetic analysis. Some patients undergo blood sample collection at baseline and during and after two treatment courses (1 and 3, 1 and 5, or 3 and 5).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 15 Years

Eligibility

Inclusion Criteria:

• Diagnosis of high-risk neuroblastoma

• Enrolled on the COG protocol ANBL0032 or ANBL0931 and eligible to receive ch14.18 according to the criteria on these primary treatment protocols

• Parental informed consent and verbal assent of the subject when appropriate

Exclusion Criteria:

• Prior testing demonstrating the presence of HACA

• Anaphylactic reaction to ch14.18 on a prior treatment cycle

Related Conditions & MeSH terms

• Localized Resectable Neuroblastoma
• Localized Unresectable Neuroblastoma
• Neuroblastoma
• Neurotoxicity Syndrome
• Neurotoxicity Syndromes
• Pain
• Regional Neuroblastoma
• Stage 4 Neuroblastoma
• Stage 4S Neuroblastoma

Intervention

Other:
• Cytology Specimen Collection Procedure
Correlative studies
• Pharmacological Study
Correlative studies

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK parameters of monoclonal antibody ch14.18 in children with high?risk neuroblastoma during and after 4 daily 10?hour infusions	PK parameters include the peak concentration, trough concentration, AUC, clearance, volume of distribution, half-life, and mean residence time. PK parameters will be derived from the plasma concentration-time data. A one-compartment model fit to the concentration-time data will estimated the volume of distribution and the first order elimination rate constant, which will in turn be used to calculate clearance, half-life, AUC0-infinity, AUC0-last, and the mean residence time. An error function and the dependency for each fitted parameter will be reported.	Before and after infusion on days 3-5; before, after, 4-6 hours after, and 12-14 hours after infusion on day 6; on the morning of days 10, 14, 17, and 24; and before infusion on day 31
Primary	Coefficient of variation of monoclonal antibody ch14.18 clearance	The coefficient of variation of Ch14.18 clearance is used to quantify the degree of inter-patient and intra-patient variability of monoclonal antibody ch14.18 pharmacokinetics. The relationship between patient characteristics, HACA, tumor burden, and plasma GD2 levels will be assessed graphically in an exploratory fashion with regression models.	Up to 58 days
Secondary	Severity of neuropathic pain, quantified using an observational pain scale based on the Face, Legs, Activity, Cry, Consolability scale (FLACC) and the total dose of morphine delivered	The pain measures will be correlated with plasma concentrations of monoclonal antibody ch14.18 simulated using the PK model and the monoclonal antibody ch14.18 AUC0-96 hours. The overall drug exposure during the infusion will be correlated with the total morphine dose administered over the 4 days of treatment.	Up to 58 days
Secondary	AUC of Ch14.18	A limited sampling strategy that will accurately quantify the AUC of monoclonal antibody ch14.18 will be developed.	Up to 58 days
Secondary	Alternative dosing strategies	Alternative dosing strategies will be simulated with the pharmacokinetic model in order to reduce variability and simplify drug administration.	Up to 58 days