Localized Resectable NeuroblastomaNCT01418495
Pharmacokinetics of Ch14.18 in Younger Patients With High-Risk Neuroblastoma
An observational study of Localized Resectable Neuroblastoma and Localized Unresectable Neuroblastoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 15 years
- Conditions the study is for
- Localized Resectable Neuroblastoma, Localized Unresectable Neuroblastoma, Neurotoxicity Syndrome
- What is being tested?
- Cytology Specimen Collection Procedure and Pharmacological Study
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 26 May 2011to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 15 years
- All sexes
- No healthy volunteers
- Child
Study population: Patients with high-risk neuroblastoma enrolled on Children's Oncology Group (COG) ANBL0032 or ANBL0931
Who may be able to join
- 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
Who cannot join
- Prior testing demonstrating the presence of HACA
- Anaphylactic reaction to ch14.18 on a prior treatment cycle
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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).
- Conditions
- Localized Resectable Neuroblastoma, Localized Unresectable Neuroblastoma, Neurotoxicity Syndrome, Pain, Regional Neuroblastoma, Stage 4 Neuroblastoma
- Being tested
- Cytology Specimen Collection Procedure, Pharmacological Study
- Medical subject headings
- Neurotoxicity Syndromes, Pain, Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytology Specimen Collection ProcedureOther
Also called Cytologic Sampling
Correlative studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Other: Cytology Specimen Collection Procedure; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 58 days
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Up to 58 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2011 (estimated)
- Study start26 May 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Localized Resectable NeuroblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Frank M Balis, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01418495
- Sponsor's protocol ID
- NCI-2011-02975
- Other IDs
- NCI-2011-02975, CHP-1002, CDR0000701215, CHP1002, 9122, P30CA016520
- Status last verified
- Sep 2019
- First submitted
- 16 Aug 2011
- Last updated
- 1 Oct 2019
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of the Chimeric Anti-GD2 Antibody, ch14.18, in Children With High-Risk Neuroblastoma
- ClinicalTrials.gov ID
- NCT01418495
- Acronym / sponsor ID
- NCI-2011-02975
- Conditions
- Localized Resectable Neuroblastoma, Localized Unresectable Neuroblastoma, Neurotoxicity Syndrome, Pain, Regional Neuroblastoma, Stage 4 Neuroblastoma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 26 May 2011 (actual)
- First posted
- 17 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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 design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ancillary-Correlative (pharmacokinetics of ch14.18) | – | Other: Cytology Specimen Collection Procedure, Other: Pharmacological StudyPatients 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). |
Who may qualify
- Ages
- Up to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Patients with high-risk neuroblastoma enrolled on Children's Oncology Group (COG) ANBL0032 or ANBL0931
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- Prior testing demonstrating the presence of HACA
- Anaphylactic reaction to ch14.18 on a prior treatment cycle
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytology Specimen Collection ProcedureAlso: Cytologic SamplingCorrelative studies | Other | Ancillary-Correlative (pharmacokinetics of ch14.18) |
| Pharmacological StudyCorrelative studies | Other | Ancillary-Correlative (pharmacokinetics of ch14.18) |
Primary outcome
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
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
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.
3 secondary outcomes
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
AUC of Ch14.18
Time frame: Up to 58 days
Alternative dosing strategies
Time frame: Up to 58 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank M Balis principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Localized Resectable Neuroblastoma and Localized Unresectable Neuroblastoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2019.