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PEPN22P1, A Pharmacokinetic Study of VinCRIStine in Infants Dosed According to BSA-Banded Infant Dosing Tables and Older Children Dosed by Traditional BSA Methods

Primary Investigator
Mody, Rajen
Status
OPEN TO ACCRUAL
Phase
Early Phase I
NCT Number
NCT05359237
UM Number
2022.122
Age Group
Children
Management Group
CTSU - Oncology
Oncology Group
Childhood Cancers
ID (Protocol)
44635
Secondary Protocol No
HUM00227109
Scope
National
Sponsor Type
Institutional
Disease Site
Bones and Joints
Brain and Nervous System
Eye and Orbit
Hodgkin's Lymphoma
Ill-Defined Sites
Kidney
Leukemia, other
Liver
Lymphoid Leukemia
Myeloid and Monocytic Leukemia
Non-Hodgkin's Lymphoma
Soft Tissue
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.

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) 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: 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