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

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

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.

Study Overview

• Status: Completed
• Conditions: Pain; Localized Resectable Neuroblastoma; Localized Unresectable Neuroblastoma; Regional Neuroblastoma; Stage 4S Neuroblastoma; Stage 4 Neuroblastoma; Neurotoxicity Syndrome
• Intervention / Treatment: Other: Pharmacological Study; Other: Cytology Specimen Collection Procedure

Detailed 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).

• Study Type: Observational
• Enrollment (Anticipated): 12

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with high-risk neuroblastoma enrolled on Children's Oncology Group (COG) ANBL0032 or ANBL0931

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ancillary-Correlative (pharmacokinetics of ch14.18); 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).	Other: Pharmacological Study; Correlative studies; Other: Cytology Specimen Collection Procedure; Correlative studies; Other Names: Cytologic Sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Frank M Balis, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2011

Study Registration Dates

• First Submitted: August 16, 2011
• First Submitted That Met QC Criteria: August 16, 2011
• First Posted (Estimate): August 17, 2011

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 30, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Poisoning; Neuroectodermal Tumors, Primitive, Peripheral; Neurotoxicity Syndromes; Neuroblastoma
• Other Study ID Numbers: NCI-2011-02975 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA016520 (U.S. NIH Grant/Contract); CHP-1002; CDR0000701215; CHP1002 (Other Identifier: Children's Hospital of Philadelphia); 9122 (Other Identifier: CTEP)