Clinical trial NCT05844670: CHildren Treated With Vincristine: A Trial Regarding Pharmacokinetics, DNA And Toxicity of Targeted Therapy In Pediatric Oncology Patients.
Official title: CHildren Treated With Vincristine: A Trial Regarding Pharmacokinetics, DNA And Toxicity of Targeted Therapy In Pediatric Oncology Patients.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pediatric Cancer
Keywords: Pharmacokinetics
Vincristine-induced peripheral neuropathy
Pediatric oncology
Vincristine
Individualized dosing
Lead sponsor: Moi University
Sponsor class: OTHER
Collaborators: name: Princess Maxima Center for Pediatric Oncology
name: Amsterdam UMC, location VUmc
First posted: 2023-05-06
Enrollment: 100
Sex: ALL
Minimum age (years): 2
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This will be a prospective cohort study.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to individualize the dosage of vincristine, a chemotherapy drug, in children with cancer. The main question it aims to answer is: can vincristine dosage be optimized while carefully monitoring toxicity.

The following will happen:

* Participants will receive vincristine according to the institutional treatment protocol.
* After receiving vincristine, blood samples will be taken at three time points.
* The amount of vincristine in the blood samples will be determined.
* If the amount of vincristine in the blood samples is lower than the reference and the participants do not experience toxicity due to vincristine, the dose of vincristine may be increased.
* Toxicity will be carefully monitored.

Detailed description: Vincristine is among the most widely used and potentially effective chemotherapeutic agents in pediatric oncology patients. However, in black African children it may be sub optimally dosed due to genetic differences in the metabolism of vincristine. This study aims to optimize the dosing regimen of vincristine while carefully monitoring toxicity.

This will be a prospective cohort study consisting of two parts: a feasibility study and the rest of the study. In the feasibility study, 15 children aged 5-14 years who are scheduled to receive at least 2 vincristine administrations can be included. After the administration of vincristine, venous blood samples and finger prick blood samples will be taken to determine the vincristine concentrations. The samples will be shipped to and analyzed in the Netherlands to determine the vincristine concentration in each sample. Based on this, a dose advise will be given for subsequent vincristine administrations. This cycle will be repeated maximum 2 times but maximum 1 dose advice is given. Toxicity will be monitored by determination of the bilirubin, by questionnaires and by physical examination to check for signs of peripheral neuropathy. In the rest of the study, in which 85 children will be included, only finger prick samples will be taken.

Eligibility criteria: Feasibility study:

Inclusion Criteria:

* Black patients aged 5-14 years with a malignancy for which they are scheduled to receive a minimum of two VCR administrations as part of their treatment protocol: acute lymphoblastic leukemia, non-Hodgkin's lymphoma, rhabdomyosarcoma, neuroblastoma, nephroblastoma, retinoblastoma.
* Written informed consent

Exclusion Criteria:

* Severe malnutrition
* Total bilirubin \>3 times upper limit of normal
* Pre-existent severe mental retardation e.g. Down syndrome
* Pre-existent peripheral neuropathy (CTCAE constipation, peripheral sensory neuropathy, peripheral motor neuropathy, or neuralgia ≥ 2 or ped-mTNS ≥ 5)

Rest of the study:

Inclusion Criteria:

* Black patients aged 2-14 years with a malignancy for which they are scheduled to receive a minimum of four VCR administrations as part of their treatment protocol: acute lymphoblastic leukemia, non-Hodgkin's lymphoma, rhabdomyosarcoma, neuroblastoma, nephroblastoma, retinoblastoma.
* Written informed consent

Exclusion Criteria:

* Severe malnutrition
* Total bilirubin \>3 times upper limit of normal
* Pre-existent severe mental retardation e.g. Down syndrome
* Pre-existent peripheral neuropathy (CTCAE constipation, peripheral sensory neuropathy, peripheral motor neuropathy, or neuralgia ≥ 2 or ped-mTNS ≥ 5)

Primary outcomes:
measure: Adapting vincristine dosage
timeFrame: Through study completion, an average of four months per patient (depending on treatment protocol).
Secondary outcomes:
measure: Vincristine-induced peripheral neuropathy
timeFrame: Through study completion, an average of four months per patient (depending on treatment protocol).
measure: Genetics
timeFrame: Through study completion, an average of four months per patient (depending on treatment protocol).
measure: Vincristine pharmacokinetics
timeFrame: Through study completion, an average of four months per patient (depending on treatment protocol).
Other outcomes:
Locations:
city: Eldoret
country: Kenya
facility: Moi Teaching and Referral Hospital
state: Rift Valley
Study officials:
affiliation: Moi University
name: Festus M Njuguna, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: