Clinical trial NCT01418495: Pharmacokinetics of Ch14.18 in Younger Patients With High-Risk Neuroblastoma
Official title: Pharmacokinetics of the Chimeric Anti-GD2 Antibody, ch14.18, in Children With High-Risk Neuroblastoma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Localized Resectable Neuroblastoma
Localized Unresectable Neuroblastoma
Neurotoxicity Syndrome
Pain
Regional Neuroblastoma
Stage 4 Neuroblastoma
Stage 4S Neuroblastoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2011-08-17
Enrollment: 12
Sex: ALL
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with high-risk neuroblastoma enrolled on Children's Oncology Group (COG) ANBL0032 or ANBL0931

Brief 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: PK parameters of monoclonal antibody ch14.18 in children with high?risk neuroblastoma during and after 4 daily 10?hour infusions
timeFrame: 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
measure: Coefficient of variation of monoclonal antibody ch14.18 clearance
timeFrame: Up to 58 days
Secondary outcomes:
measure: 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
timeFrame: Up to 58 days
measure: AUC of Ch14.18
timeFrame: Up to 58 days
measure: Alternative dosing strategies
timeFrame: Up to 58 days
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Frank M Balis
role: PRINCIPAL_INVESTIGATOR
References: