Vincristine Pharmacokinetics in Infants
M
Melissa Bear, MD
Primary Investigator
Overview
This pilot trial compares drug exposure levels using a new method for dosing vincristine ind young children compared to the standard dosing method based on body surface area
(BSA) in older children. Vincristine is an anticancer drug used to a variety of childhood. The doses anticancer drugs in children must be adjusted based on the size of thehild because children vary significantly in size (height, weight, and BSA) and ability tobolize drugs from infancy to adolescence. The dose of most anticancer drugs is adjustedBSA, which is calculated from a patient's weight and height. However, infants and younghildren have more severe side effects if the BSA is used to calculate their dose, so new
dosing models have to be made to safely give anticancer drugs to the youngest patients. Thisw method uses a BSA-banded approach to determine the dose. Collecting blood samples befored after a dose of the drug will help researchers determine whether this new vincristine
dosing method results in equivalent drug levels in the blood over time in infants and younghildren compared to older children.
Description
PRIMARY OBJECTIVE:
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 eliminationhase (AUCelim), in infants and young children dosed according to the table to older children
dosed according to BSA.
SECONDARY OBJECTIVE:
I. To estimate intra- and inter-age group variability (CV) using non-compartmental analysis
(NCA) and population pharmacokinetic (PK) methods.
EXPLORATORY OBJECTIVES:
I. To correlate higher AUCelim with the presence of functionally impaired single nucleotideymorphisms (SNP) of CYP3A4 and CYP3A5.
II. To assess vinCRIStine dose modifications in infants receiving weekly vinCRIStine dosedding to the BSA-banded infant dosing tables.
TLINE
Patients receive vincristine intravenously (IV) per standard of care. Patients undergoblood 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 bloodwith 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).
Eligibility
You may be eligible for this study if you meet the following criteria:
-
Conditions:
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
-
Age: - 12 Years
-
Gender: All
Inclusion Criteria:
- Patients must be =< 12 years of age at the time of study enrollment. Patients will bed 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) canve a dose of vincristine from the infant dosing table for the pharmacokineticudy. These patients will NOT be part of the Dose Modification Assessment
- Patients with a seizure disorder may be enrolled if on allowable anticonvulsants andwell 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 bed, which will require return for hour 24 sampling
Exclusion Criteria:
- Azoles antifungals and macrolide antibiotics: Patients who are currently receiving anzole or macrolide (e.g., fluconazole, isavuconazole, itraconazole, posaconazole,voriconazole, ketoconazole, eryromycin, clarithromycin, azithromycin, roxithromycin,hromycin) are not eligible
- CYP3A4/5 inducers/inhibitors: Patients receiving any medications or substances thatdered moderate or strong inhibitors or inducers of CYP3A4/5 are not eligible.derate or strong inducers or inhibitors of CYP3A4/5 should be avoided from 14 dayshe end of the study. Note: dexamethasone for central nervousystem (CNS) tumors or metastases, on a stable dose, is allowed
- Anticonvulsants: Patients receiving moderate or strong CYP3A4/5 enzyme inducingvulsants are not eligible.
- Patients with Charcot-Marie-Tooth disease
- A baseline neurological disorder with manifestations that overlap withvinCRIStine-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 theg requirements of the study
Updated on
03 May 2024.
Study ID: PEPN22P1
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