CHildren Treated With Vincristine: A Trial Regarding Pharmacokinetics, DNA And Toxicity of Targeted Therapy In Pediatric Oncology Patients.

NCT ID: NCT05844670

Last Updated: 2023-05-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-20
• Study Completion Date: 2024-11-01

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.

Conditions

Pediatric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vincristine

A dose advice for vincristine will be given based on vincristine concentrations in blood samples and toxicity monitoring.

Group Type: EXPERIMENTAL

Vincristine

Intervention Type: DRUG

The initial vincristine dosage will be according to institutional treatment protocol. After vincristine administration, three blood samples will be taken at T=1, T=1.5 and T=4 hours. The concentration of vincristine will be analyzed in the samples. If the concentration of 2 or more samples is lower than the reference concentration and there is no toxicity, an advice will be given to increase dosage by 20%. Whether or not a dosage is given, vincristine concentrations will be measured again for the next dose administration.

For the feasibility study, both venous blood samples and finger prick blood samples using Mitra tips will be taken. The cycle can be repeated maximum 2 times.

For the rest of the study, finger prick blood samples using Mitra tips will be taken. The cycle can be repeated maximum 3 times.

Toxicity will be monitored through physical exam and questionnaire, bilirubin levels and clinical status of the patient.

Interventions

Vincristine

The initial vincristine dosage will be according to institutional treatment protocol. After vincristine administration, three blood samples will be taken at T=1, T=1.5 and T=4 hours. The concentration of vincristine will be analyzed in the samples. If the concentration of 2 or more samples is lower than the reference concentration and there is no toxicity, an advice will be given to increase dosage by 20%. Whether or not a dosage is given, vincristine concentrations will be measured again for the next dose administration.

For the feasibility study, both venous blood samples and finger prick blood samples using Mitra tips will be taken. The cycle can be repeated maximum 2 times.

For the rest of the study, finger prick blood samples using Mitra tips will be taken. The cycle can be repeated maximum 3 times.

Toxicity will be monitored through physical exam and questionnaire, bilirubin levels and clinical status of the patient.

Intervention Type: DRUG

Eligibility Criteria

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

• 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)

Rest of the study:

• 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)

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Princess Maxima Center for Pediatric Oncology

OTHER

Sponsor Role: collaborator

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: collaborator

Moi University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Festus M Njuguna, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Moi University

Locations

Moi Teaching and Referral Hospital

Eldoret, Rift Valley, Kenya

Site Status: RECRUITING

Countries

Kenya

Central Contacts

Aniek Uittenboogaard, MD

Role: CONTACT

a.uittenboogaard@amsterdamumc.nl

+31631293157

Festus M Njuguna, MD, PhD

Role: CONTACT

muigaifes2000@yahoo.com

+254532032393

Facility Contacts

Aniek Uittenboogaard, MD

Role: primary

a.uittenboogaard@amsterdamumc.nl

+31631293157

Festus M Njuguna, MD, PhD

Role: backup

muigaifes2000@yahoo.com

+254532032393

Other Identifiers

V314092022

Identifier Type: -

Identifier Source: org_study_id