Vincristine Pharmacokinetics in Infants

Malignant Solid Neoplasm Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05359237
• Other study ID #: PEPN22P1
• Secondary ID: NCI-2022-03576PE
• Status: Recruiting
• Start date: November 16, 2022
• Est. completion date: July 31, 2024

Study information

• Verified date: March 2024
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This pilot trial compares drug exposure levels using a new method for dosing vincristine in infants and 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 cancers. The doses anticancer drugs in children must be adjusted based on the size of the child because children vary significantly in size (height, weight, and BSA) and ability to metabolize drugs from infancy to adolescence. The dose of most anticancer drugs is adjusted to BSA, which is calculated from a patient's weight and height. However, infants and young children 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. This new method uses a BSA-banded approach to determine the dose. Collecting blood samples before and 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 young children 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 elimination phase (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 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.

OUTLINE:

Patients receive vincristine intravenously (IV) per standard of care (SOC). 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 SOC vincristine dose at the same time points.

Patients are followed for dose modifications for a period of 42 days (when receiving weekly dosing of vincristine).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 74
• Est. completion date: July 31, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 12 Years

Eligibility

Inclusion Criteria:

• 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) or scheduled to be placed prior to the dose of vinCRIStine and 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

Exclusion Criteria:

• 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 the following are allowed:

• Dexamethasone for CNS tumors or metastases, on a stable dose

• Aprepitant for management of nausea and vomiting

• 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 being treated on a Children Oncology Group (COG) clinical trial, that does not use the infant dosing tables for vinCRIStine are not eligible for this study.

• 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

Related Conditions & MeSH terms

• Hematopoietic and Lymphoid Cell Neoplasm
• Malignant Solid Neoplasm
• Neoplasms

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood samples

Drug:
• Vincristine
Given IV per standard of care

Locations

Country	Name	City	State
Australia	Queensland Children's Hospital	South Brisbane	Queensland
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Lurie Children's Hospital-Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Saint Jude Children's Research Hospital	Memphis	Tennessee
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlation of AUC for the elimination phase with CYP3A4 and CYP3A5 single nucleotide polymorphisms (SNPs)	Correlate AUCelim with the presence of functionally impaired single nucleotide polymorphisms (SNP) of CYP3A4 and CYP3A5.	Up to 24 hours
Other	Number of patients requiring vincristine dose modifications	Number of patients requiring vincristine dose modifications stratified by age group.	Up to 42 days
Primary	Area under the concentration time curve for the elimination phase (AUCelim) by age group	Estimate (95% CI) of the mean area under the concentration time curve for the elimination phase assessed at 0, 2, 6-8, and 18-24 hours after vinCRISTine dose by age group.	Up to 24 hours post vincristine dose
Secondary	Intra- and inter-age coefficient of variation (CV)	Estimate of the intra- and inter-age coefficient of variation using non-compartmental analysis (NCA) and population pharmacokinetic (PK) methods.	Up to 42 days