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

15 Years
Open (Enrolling)
Disseminated Neuroblastoma, Localized Resectable Neuroblastoma, Localized Unresectable Neuroblastoma, Neurotoxicity, Pain, Regional Neuroblastoma, Stage 4S Neuroblastoma, Therapy-related Toxicity

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Trial Information

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


I. Describe the pharmacokinetics (PKs) of monoclonal antibody Ch14.18 (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 G_D2 levels to
identify sources of variability in the clearance.

III. (Exploratory) Develop a PK model to describe the PK profile of Ch14.18 and derive PK


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 PK model in order to reduce variability
and simplify drug administration.


Patients undergo blood sample collection at baseline and during and after course 1, 3, or 5
of monoclonal antibody Ch14.18 (Ch14.18) and sargramostim for pharmacokinetic, human
anti-chimeric antibody, and concentration of ganglioside G_D2 studies. The Ch14.18A level is
measured via ELISA. A pharmacokinetic model is then developed using the Modeling Laboratory
(MLAB) software.

Parents, guardians, or caretakers are asked to assess patients' pain three times a day,
prior to, during, and at the end of Ch14.18 treatment.

Inclusion Criteria:

- Diagnosis of high-risk neuroblastoma

- Enrolled on the Children Oncology Group (COG) protocol ANBL0032 or ANBL0931 and
eligible to receive monoclonal antibody Ch14.18 according to the criteria on these
primary treatment protocols

- No prior testing demonstrating the presence of human anti-chimeric antibody (HACA)

- No anaphylactic reaction to monoclonal antibody Ch14.18 on a prior treatment cycle

Type of Study:


Study Design:

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

PK parameters of Ch14.18 in children with high‐risk neuroblastoma during and after 4 daily 10‐hour infusions, including the peak concentration, trough concentration, AUC, clearance, volume of distribution, half-life, and mean residence time

Outcome Description:

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.

Outcome Time Frame:

Before and after infusion on days 3-5; before, after, and 4-6 hours after infusion on day 6; 12-14 hours after infusion on day 7; on the morning of days 10, 14, 17, and 24; and before infusion on day 31

Safety Issue:


Principal Investigator

Frank Balis

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Hospital of Philadelphia


United States: Food and Drug Administration

Study ID:




Start Date:

May 2011

Completion Date:

Related Keywords:

  • Disseminated Neuroblastoma
  • Localized Resectable Neuroblastoma
  • Localized Unresectable Neuroblastoma
  • Neurotoxicity
  • Pain
  • Regional Neuroblastoma
  • Stage 4S Neuroblastoma
  • Therapy-related Toxicity
  • Neuroblastoma
  • Neurotoxicity Syndromes



Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104