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

April 25, 2023 updated by: Moi University

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Kenya
    • Rift Valley
      • Eldoret, Rift Valley, Kenya, P.o. Box 3-30100

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vincristine
A dose advice for vincristine will be given based on vincristine concentrations in blood samples and toxicity monitoring.
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adapting vincristine dosage
Time Frame: Through study completion, an average of four months per patient (depending on treatment protocol).
The number of patients in whom it is possible to adapt vincristine dosage based on vincristine concentrations in the blood at three time points and the presence of side-effects.
Through study completion, an average of four months per patient (depending on treatment protocol).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vincristine-induced peripheral neuropathy
Time Frame: Through study completion, an average of four months per patient (depending on treatment protocol).
The number of patients who develop vincristine-induced peripheral neuropathy (VIPN) and the degree of VIPN. VIPN is measured using the CTCAE v5 items peripheral sensory neuropathy, peripheral motor neuropathy, neuralgia and constipation. In children aged 5 or above, VIPN will also be assessed with the ped-mTNS.
Through study completion, an average of four months per patient (depending on treatment protocol).
Genetics
Time Frame: Through study completion, an average of four months per patient (depending on treatment protocol).
The association between pharmacogenomic parameters and the concentration of vincristine at three time points (T=60 minutes, T=90 minutes and T=240 minutes after vincristine administration) and vincristine-induced peripheral neuropathy using CTCAE v5 and ped-mTNS.
Through study completion, an average of four months per patient (depending on treatment protocol).
Vincristine pharmacokinetics
Time Frame: Through study completion, an average of four months per patient (depending on treatment protocol).
The median vincristine concentrations and interquartile ranges (IQR) on three time points (T=60 minutes, T=90 minutes and T=240 minutes after vincristine administration).
Through study completion, an average of four months per patient (depending on treatment protocol).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Moi University

Collaborators

Amsterdam UMC, location VUmc
Princess Maxima Center for Pediatric Oncology

Investigators

  • Principal Investigator: Festus M Njuguna, MD, PhD, Moi University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 20, 2023

Primary Completion (Anticipated)

August 1, 2024

Study Completion (Anticipated)

November 1, 2024

Study Registration Dates

First Submitted

April 13, 2023

First Submitted That Met QC Criteria

April 25, 2023

First Posted (Estimate)

May 4, 2023

Study Record Updates

Last Update Posted (Estimate)

May 4, 2023

Last Update Submitted That Met QC Criteria

April 25, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • V314092022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The data are available upon reasonable request.

IPD Sharing Time Frame

The study protocol and ICF is already available upon request. Upon completion of the study, the SAP, CSR and analytic code will be accessible for unlimited amount of time.

IPD Sharing Access Criteria

The data are available upon reasonable request.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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