| Protocol No: | ECCT/24/02/05 | Date of Protocol: | 21-12-2021 |
| Study Title: | Pharmacokinetic profiles for Doxorubicin among children with childhood cancer in Kenya.
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| Study Objectives: |
Primary Objective:
To evaluate the PK profiles of Doxorubicin in children with cancer in Lilongwe-Malawi and Eldoret-Kenya.
Secondary objectives:
1. To evaluate the PK profiles of Doxorubicin and Doxorubicinol in relation to age
2. To evaluate the PK profiles of Doxorubicin and Doxorubicinol in relation to nutritional status
3. To evaluate the PK profiles of Doxorubicin and Doxorubicinol in relation to genetic
polymorphisms
4. To evaluate the PK profiles of Doxorubicin and Doxorubicinol in relation to racial background.
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| Laymans Summary: | ABSTRACT
Background: Cancer is a leading cause of death among children worldwide. Doxorubicin has been an effective backbone for several childhood cancer treatment protocols; however, cardio toxicity often limits the clinical use. Pharmacokinetics (PK) are extremely important in predicting safe and effective chemotherapy but data for Doxorubicin with regard to nutritional status and genetic polymorphisms associated with drug metabolism among different ethnicities is largely lacking.
Relevance of the study: More knowledge about the PK of Doxorubicin among children with varying ages, different nutritional profiles, as well as different ethnicities, in the view of possible genetic polymorphisms is extremely important to improve short- and long-term outcomes. Better understanding of these variables could lead to a reduction in treatment-related toxicity and a more effective treatment for children with cancer worldwide.
Aim: We aim to evaluate the PK of Doxorubicin in children with cancer receiving Doxorubicin-based regimens in Eldoret-Kenya. The data generated will be used to determine a more appropriate Doxorubicin dosing regimen in different patient populations with respect to age, nutritional status and ethnicity. Based on a pharmacological rationale we hypothesize that PK-profiles for Doxorubicin in children with different ages, nutritional profiles and ethnicities will significantly differ.
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| Abstract of Study: | ABSTRACT
Background: Cancer is a leading cause of death among children worldwide. Doxorubicin has been an effective backbone for several childhood cancer treatment protocols; however, cardio toxicity often limits the clinical use. Pharmacokinetics (PK) are extremely important in predicting safe and effective chemotherapy but data for Doxorubicin with regard to nutritional status and genetic polymorphisms associated with drug metabolism among different ethnicities is largely lacking.
Relevance of the study: More knowledge about the PK of Doxorubicin among children with varying ages, different nutritional profiles, as well as different ethnicities, in the view of possible genetic polymorphisms is extremely important to improve short- and long-term outcomes. Better understanding of these variables could lead to a reduction in treatment-related toxicity and a more effective treatment for children with cancer worldwide.
Aim: We aim to evaluate the PK of Doxorubicin in children with cancer receiving Doxorubicin-based regimens in Eldoret-Kenya. The data generated will be used to determine a more appropriate Doxorubicin dosing regimen in different patient populations with respect to age, nutritional status and ethnicity. Based on a pharmacological rationale we hypothesize that PK-profiles for Doxorubicin in children with different ages, nutritional profiles and ethnicities will significantly differ.
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| 1 |
I am writing to request for amendments for protocol titled: “Pharmacokinetic profiles for
Doxorubicin among children with childhood cancer in Kenya”
1. Summary of the proposed amendments
Dropping pharmacokinetic sample 5 (48th hour sample)
2. Justification for the amendment
A power analysis was performed, excluding the 48-hour time point. In this case, the 80%
power threshold was met with 25 participants, and a sample size of 80 would still yield
around 99% power.
These findings indicate that enrolling 80 participants remains a viable approach even if
the 48-hour time point is omitted.
3. Impact of the amendment on the original study objectives
The omission of the 48-hour pharmacokinetic sample is not expected to affect the
achievement of the study objectives. The power analysis confirms that the planned
sample size has adequate statistical power. The overall objectives to evaluate the PK
profiles of Doxorubicin and Doxorubicinol in relation to age, nutritional status, genetic
polymorphisms, ethnicity, and comparison with a Dutch population remain achievable.
4. Impact of the amendments on the study endpoints and data generated.
The amendment request to omit the 48-hour pharmacokinetic sample will not adversely
affect the study's ability to meet its stated endpoints or compromise the overall quality
and integrity of the data generated.
The primary pharmacokinetic endpoints remain fully supported by the sampling
schedule, and the robustness of these measures has been confirmed through power
analysis. As such, the omission of this single late time point does not diminish the
scientific validity of the study or the reliability of the findings.
5. Impact of the proposed amendments on the safety and well-being of study
participants
The omission of the 48-hour pharmacokinetic sample will in no way compromise the
safety or well-being of study participants. All essential safety assessments, including
clinical evaluations, laboratory monitoring, and adverse event reporting, will continue to
be performed in accordance with the study protocol.
The standard procedures for clinical oversight remain fully intact, ensuring that the
protection of participants’ health and welfare is maintained throughout the study
without any reduction in the rigor or completeness of safety monitoring.
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