Vincristine Pharmacokinetics in Infants
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|ClinicalTrials.gov Identifier: NCT05359237|
Recruitment Status : Recruiting
First Posted : May 3, 2022
Last Update Posted : March 28, 2023
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|Condition or disease||Intervention/treatment|
|Hematopoietic and Lymphoid Cell Neoplasm Malignant Solid Neoplasm||Procedure: Biospecimen Collection Drug: Vincristine|
I. To validate body surface area (BSA)-banded infant dosing tables by comparing vinCRIStine drug exposure, defined as the area under the concentration-time curve for the elimination phase (AUCelim), in infants and young children dosed according to the table to older children dosed according to BSA.
I. To estimate intra- and inter-age group variability (CV) using non-compartmental analysis (NCA) and population pharmacokinetic (PK) methods.
I. To correlate higher AUCelim with the presence of functionally impaired single nucleotide polymorphisms (SNP) of CYP3A4 and CYP3A5.
II. To assess vinCRIStine dose modifications in infants receiving weekly vinCRIStine dosed according to the BSA-banded infant dosing tables.
Patients receive vincristine intravenously (IV) per standard of care. Patients undergo collection of blood samples at baseline (before first vincristine dose), and 2, 6-8, and 18-24 hours after a dose of vincristine. Patients may also undergo collection of blood samples with a second vincristine dose at the same time points.
Patients are followed for dose modifications for a period of 6 weeks (when receiving weekly dosing of vincristine).
|Study Type :||Observational|
|Estimated Enrollment :||59 participants|
|Official Title:||A Pharmacokinetic Study of VinCRIStine in Infants Dosed According to BSA-Banded Infant Dosing Tables and Older Children Dosed by Traditional BSA Methods|
|Actual Study Start Date :||November 14, 2022|
|Estimated Primary Completion Date :||July 31, 2024|
|Estimated Study Completion Date :||July 31, 2024|
Treatment (vincristine, biospecimen collection)
Patients receive vincristine IV per standard of care. Patients undergo collection of blood samples at baseline (before first vincristine dose), and 2, 6-8, and 18-24 hours after a dose of vincristine. Patients may also undergo collection of blood samples with a second vincristine dose at the same time points.
Procedure: Biospecimen Collection
Undergo collection of blood samples
- Change in area under the concentration time curve for the elimination phase by age in months [ Time Frame: Up to 24 hours post vincristine dose ]Estimate (95% CI) of the change in area under the concentration time curve for the elimination phase by age of patient (in months).
- Determine intra- and inter-age group variability (CV) [ Time Frame: Up to 2 years ]Estimate using non-compartmental analysis (NCA) and population pharmacokinetic (PK) methods.
- Understand impact of pharmacogenomics [ Time Frame: Up to 2 years ]Correlate AUCelim with the presence of functionally impaired single nucleotide polymorphisms (SNP) of CYP3A4 and CYP3A5.
- Frequency of patients requiring dose modifications for toxicity to vinCRISTine. [ Time Frame: up to 42 days ]Frequency (%) of patients requiring dose modifications for toxicity to vinCRISTine stratified by age group.
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|Ages Eligible for Study:||up to 12 Years (Child)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
|Sampling Method:||Probability Sample|
Patients must be =< 12 years of age at the time of study enrollment. Patients will be stratified into 4 age groups:
- 0 to 6 months
- 6 months and 1 day to 12 months
- 12 months and 1 day to 36 months
- 36 months and 1 day to 12 years
- Newly diagnosed and relapsed cancer diagnosis that is being treated with vinCRIStine at the 1.5 mg/m^2 dose level
- Any disease status
- Patients must have a Lansky performance status of 50 or higher
- Patients must be receiving a treatment regimen that includes 1.5 mg/m^2 vinCRIStine (maximum dose 2 mg)
Patients with a BSA < 0.6 m^2 must be dosed according to the Children's Oncology Group (COG) BSA-banded infant dosing table for the 1.5mg/m2 dose level for vinCRIStine
- Note: Patients can be studied after any dose of vinCRIStine
- Patients who are NOT enrolled on a COG clinical trial and who have a BSA < 0.6 m^2 and who are being dosed according to another infant dosing method (e.g., the 30-Rule) can receive a dose of vincristine from the infant dosing table for the pharmacokinetic study. These patients will NOT be part of the Dose Modification Assessment
- Patients with a seizure disorder may be enrolled if on allowable anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
- Nervous system toxicities (Common Terminology Criteria for Adverse Events [CTCAE]) version (v)5 resulting from prior therapy must be grade =< 2
- Central venous access device in place (e.g., percutaneous indwelling central catheter [PICC], port, Broviac) that can be used for pharmacokinetic (PK) sampling
- VinCRIStine may be given as an outpatient, as long as all sample time points can be collected, which will require return for hour 24 sampling
- Azoles antifungals and macrolide antibiotics: Patients who are currently receiving an azole or macrolide (e.g., fluconazole, isavuconazole, itraconazole, posaconazole, voriconazole, ketoconazole, eryromycin, clarithromycin, azithromycin, roxithromycin, or telithromycin) are not eligible
- CYP3A4/5 inducers/inhibitors: Patients receiving any medications or substances that are considered moderate or strong inhibitors or inducers of CYP3A4/5 are not eligible. Moderate or strong inducers or inhibitors of CYP3A4/5 should be avoided from 14 days prior to enrollment to the end of the study. Note: dexamethasone for central nervous system (CNS) tumors or metastases, on a stable dose, is allowed
- Anticonvulsants: Patients receiving moderate or strong CYP3A4/5 enzyme inducing anticonvulsants are not eligible.
- Patients with Charcot-Marie-Tooth disease
- A baseline neurological disorder with manifestations that overlap with vinCRIStine-associated neurotoxicities
- Patients receiving a modified dose (< 1.5 mg/m^2) of vinCRIStine due to prior toxicity
- Patients who in the opinion of the investigator may not be able to comply with the sampling requirements of the study
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05359237
|Principal Investigator:||Emily Blauel||Pediatric Early Phase Clinical Trial Network|
|Responsible Party:||Children's Oncology Group|
|Other Study ID Numbers:||
NCI-2022-03576 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PEPN22P1 ( Other Identifier: Pediatric Early Phase Clinical Trial Network )
PEPN22P1 ( Other Identifier: CTEP )
UM1CA228823 ( U.S. NIH Grant/Contract )
|First Posted:||May 3, 2022 Key Record Dates|
|Last Update Posted:||March 28, 2023|
|Last Verified:||March 2023|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Antineoplastic Agents, Phytogenic
Molecular Mechanisms of Pharmacological Action