| Protocol No: | ECCT/22/03/05 | Date of Protocol: | 05-12-2019 |
| Study Title: | CHildren treated with vincristine: A trial regarding Pharmacokinetics, DNA And Toxicity of targeted therapy In pediatric oncology patients. |
| Study Objectives: | 1. To determine the optimal vincristine dose among children receiving chemotherapy at MTRH 2. To evaluate the development and severity of peripheral neuropathy and liver toxicity in paediatric oncology patients receiving optimized vincristine doses in MTRH 3. To study genetic variants that are associated with vincristine metabolism as well as the development and severity of peripheral neuropathy |
| Laymans Summary: | The aim of the study is to optimize treatment and improve survival for children on treatment for cancer by maximizing the use of Vincristine, a drug which is used in treatment of childhood cancer. Baseline assessment to check presence of nerve injury, bilirubin levels and malnutrition will be done before 1st administration of regular Vincristine dose. Blood sample will be obtained by a finger prick for analysis of Vincristine concentration after the dose has been given. The dose of Vincristine will be increased during the next administration when the Vincristine concentration below the level calculated as safe and in the absence of severe vincristine induced peripheral neuropathy or any other severe side effect. A second, third and fourth dose adaptation will be given if the above criteria is met after each dose adaptation. The information from this study might lead to a change in treatment of a wide range of cancers for black African children worldwide, by demonstrating that these children benefit from higher doses of VCR without severely increasing Vincristine induced peripheral neuropathy. |
| Abstract of Study: | Background: Vincristine is among the most widely used and potentially effective chemotherapeutic agents in pediatric oncology patients. However, in black African children it is often sub optimally dosed due to genetic differences in the metabolism of vincristine. This study aims to optimize the dosing regimen of vincristine using therapeutic drug monitoring while carefully monitoring toxicity. Design This will be a prospective cohort study. All children aged 2-14 years diagnosed with cancer and scheduled to receive vincristine can be included. After the administration of vincristine, blood samples will be taken. These 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 in total 3 times. Toxicity will be monitored by determination of the bilirubin, by questionnaires and by physical examination to check for signs of peripheral neuropathy. Results We aim to include 100 patients. The required dose to achieve a therapeutic vincristine level, will be compared to a historic cohort. The results will lead to an alteration in the dosing regimen of vincristine in all pediatric oncology patients in Kenya. |