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

National Cancer Institute (NCI)

Status: Completed

Conditions: Regional Neuroblastoma; Localized Unresectable Neuroblastoma; Stage 4S Neuroblastoma; Stage 4 Neuroblastoma; Pain; Neurotoxicity Syndrome; Localized Resectable Neuroblastoma

Treatments: Other: Pharmacological Study; Other: Cytology Specimen Collection Procedure

Study type: Observational

Funder types: NIH

Identifiers

NCT01418495

NCI-2011-02975 (Registry Identifier)

CHP1002 (Other Identifier)

CDR0000701215

P30CA016520 (U.S. NIH Grant/Contract)

CHP-1002

9122 (Other Identifier)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 12 estimated patients

Sex: All

Ages: Under 15 years old

Volunteers: No Healthy Volunteers

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

Trial design

12 participants in 1 patient group

Ancillary-Correlative (pharmacokinetics of ch14.18)

Description:

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).

Treatment:

Other: Cytology Specimen Collection Procedure

Other: Pharmacological Study