A Study to Measure How a New Method for Dosing Vincristine in Infants and Young Children Compares to the Standard Dosing Method in Older Children
Study Details
Study Description
Brief Summary
This early phase I trial compares a new method for dosing vincristine in infants and young children to the standard dosing method based on body size in older children. Chemotherapy drugs, such as vincristine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The same dose of a drug cannot be given to all children because they vary a lot in size from infancy to adolescence. The dose of most anticancer drugs is based on a measure of body size called the body surface area (BSA). BSA 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 adjustments have to be made to safely give anticancer drugs to the youngest patients. A new method for dosing anticancer drugs in infants and young children has been developed that uses body size to determine the dose. Collecting blood samples over time may help researchers understand how the new vincristine dosing method affects drug levels in the blood over time in infants and young children compared to older children.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
PRIMARY OBJECTIVE:
- 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 (AUC), in infants and young children dosed according to the table to older children dosed according to BSA.
SECONDARY OBJECTIVE:
- To estimate intra- and inter-age group variability (CV) using non-compartmental analysis (NCA) and population pharmacokinetic (PK) methods.
EXPLORATORY OBJECTIVES:
-
To correlate higher AUC with the presence of functionally impaired single nucleotide polymorphisms (SNP) of CYP3A4 and CYP3A5.
-
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. Patients undergo collection of blood samples at baseline (before first vincristine dose), and 2, 6-8, and 18-24 hours after first dose of vincristine. Patients may also undergo collection of blood samples before second vincristine dose, and 2, 6-8, and 18-24 hours after second dose of vincristine.
After completion of study treatment, patients are followed at 6 weeks.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 first dose of vincristine. Patients may also undergo collection of blood samples before second vincristine dose, and 2, 6-8, and 18-24 hours after second dose of vincristine. |
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
Drug: Vincristine
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Area under the concentration-time curve for the elimination phase (AUC) [Up to 2 years]
Secondary Outcome Measures
- Intra- and inter-age group variability [Up to 2 years]
Will be estimated using non-compartmental analysis (NCA) and population pharmacokinetic (PK) methods.
Other Outcome Measures
- Area under the curve [Up to 2 years]
Higher AUC will be correlated with the presence of functionally impaired single nucleotide polymorphisms (SNP) of CYP3A4 and CYP3A5.
- Vincristine dose modifications [Up to 2 years]
Vincristine dose modifications in infants receiving weekly vincristine dosed according to the BSA-banded infant dosing tables will be assessed.
Eligibility Criteria
Criteria
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
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6 months and 1 day to 12 months
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12 months and 1 day to 36 months
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36 months and 1 day to 12 years
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Newly diagnosed and relapsed cancer diagnosis that is being treated with vinCRIStine
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Any disease status
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Patients must have a Lansky performance status of 50 or higher
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Patients must be receiving a treatment regimen that includes 1.5 mg/m^2 vinCRIStine (maximum dose 2 mg)
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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
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Note: Patients can be studied after any dose of vinCRIStine
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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
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Nervous system toxicities (Common Terminology Criteria for Adverse Events [CTCAE]) version (v)5 resulting from prior therapy must be grade =< 2
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Central venous access device in place (e.g., percutaneous indwelling central catheter [PICC], port, Broviac) that can be used for pharmacokinetic (PK) sampling
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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:
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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
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Anticonvulsants: Patients receiving moderate or strong CYP3A4/5 enzyme inducing anticonvulsants are not eligible.
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Patients with Charcot-Marie-Tooth disease
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A baseline neurological disorder with manifestations that overlap with vinCRIStine-associated neurotoxicities
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Patients receiving a modified dose (< 1.5 mg/m^2) of vinCRIStine due to prior toxicity
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Patients who in the opinion of the investigator may not be able to comply with the sampling requirements of the study
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Children's Oncology Group
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Emily Blauel, Pediatric Early Phase Clinical Trial Network
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PEPN22P1
- NCI-2022-03576
- PEPN22P1
- PEPN22P1
- UM1CA228823