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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01418495
First received: August 16, 2011
Last updated: July 23, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention
Disseminated Neuroblastoma
Localized Resectable Neuroblastoma
Localized Unresectable Neuroblastoma
Neurotoxicity
Pain
Regional Neuroblastoma
Stage 4S Neuroblastoma
Drug: cytology specimen collection procedure
Other: pharmacological study

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Pharmacokinetics of the Chimeric Anti-GD2 Antibody, ch14.18, in Children With High-Risk Neuroblastoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • PK parameters of monoclonal antibody ch14.18 in children with high‐risk neuroblastoma during and after 4 daily 10‐hour infusions [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Coefficient of variation of monoclonal antibody ch14.18 clearance [ Time Frame: Up to 58 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 [ Time Frame: Up to 58 days ] [ Designated as safety issue: No ]
    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.

  • AUC of Ch14.18 [ Time Frame: Up to 58 days ] [ Designated as safety issue: No ]
    A limited sampling strategy that will accurately quantify the AUC of monoclonal antibody ch14.18 will be developed.

  • Alternative dosing strategies [ Time Frame: Up to 58 days ] [ Designated as safety issue: No ]
    Alternative dosing strategies will be simulated with the pharmacokinetic model in order to reduce variability and simplify drug administration.


Biospecimen Retention:   Samples With DNA

Blood


Enrollment: 12
Study Start Date: May 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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).
Drug: cytology specimen collection procedure
Correlative studies
Other Name: cytologic sampling
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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

Ages Eligible for Study:   up to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01418495

Locations
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Investigators
Principal Investigator: Frank Balis Children's Hospital of Philadelphia
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01418495     History of Changes
Other Study ID Numbers: NCI-2011-02975, NCI-2011-02975, CDR0000701215, CHP-1002, CHP1002, 9122
Study First Received: August 16, 2011
Last Updated: July 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neuroblastoma
Neurotoxicity Syndromes
Chemically-Induced Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Poisoning

ClinicalTrials.gov processed this record on November 25, 2014