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2020-02-18
2021-09-30
2021-09-30
250
NCT04269369
Jessa Hospital
Jessa Hospital
INTERVENTIONAL
Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
The aim of this study is to investigate if the systematic implementation of pre-emptive geno- and phenotyping, and therefore a dose reduction based on the French guidelines and the literature during the first month of treatment, reduces grade 3 or greater toxicity in patients treated with 5-FU (5-fluorouracil) or capecitabine. Therefore, a monocentric, partial prospective and partial retrospective trail was designed.
5-FU (5-fluorouracil) and its oral prodrug capecitabine are commonly used drugs in various chemotherapy regimens. According to the literature, approximately 30% of the patients experience at least a grade three toxicity during treatment, mainly characterized by diarrhea, mucositis, hematological toxicity or hand-foot syndrome. This toxicity can lead to discontinuation or interruption of the therapy, hospitalization and in 1% of the cases even to mortality. This leads to an increase in health care costs, mainly driven by the cost of hospitalization. The metabolism of 5-FU and its prodrug is primarily determined by the dehydropyrimidine dehydrogenase (DPD) enzyme. The gene encoding for this enzyme, the DPYD, is known for his genetic polymorphism. Five percent of the population has a partial DPYD deficiency and 0.01 to 0.1 percent has a full DPYP deficiency. Partial deficiency leads to a reduced activity of DPD and therefore to a reduced degradation of 5-FU or capecitabine to its inactive metabolites. This leads to an increased toxicity. The four DPYD variants considered most clinically relevant are DPYD * 2A, DPYD * 13, c.1236G> A and c.2846A> T. Patients with polymorphisms DPYD * 2A and DPYD * 13 have no residual enzyme activity, while in patients with polymorphisms 1236G> A and c.2846A> T, there is still partial enzyme activity present. In addition to genotyping, partial DPYD deficiency can also be detected by phenotyping. In the case of reduced enzyme activity of DPYD, the degradation of uracil is disturbed, causing an increase in uracil and a decrease in UH2 in plasma. There is a strong correlation between the UH2 / U ratio in plasma and the halflife, clearance and plasma levels of 5-FU. French guidelines, HAS (La Haute Autorité de santé), recommend to adjust the dose of these drugs at the start of treatment based on the results of both the genetic and phenotypic studies. The aim of this study is to investigate if the systematic implementation of pre-emptive geno- and phenotyping, and therefore a dose reduction based on the French guidelines and the literature during the first month of treatment, reduces grade 3 or greater toxicity in patients treated with 5-FU or capecitabine. Therefore, a monocentric, partial prospective and partial retrospective trail was designed.
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 Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2020-02-11 | N/A | 2020-02-12 |
2020-02-12 | N/A | 2020-02-13 |
2020-02-13 | N/A | 2020-02 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Randomized
Interventional Model:
Parallel
Masking:
None
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
| EXPERIMENTAL: Group A Dosage according to French guidelines | DRUG: 5-Fluorouracil
|
| EXPERIMENTAL: Group B Dosage according to literature | DRUG: 5-Fluorouracil
|
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| The frequency of severe fluoropyrimidine-related toxicity | The primary endpoint of the study is the frequency of severe (National Cancer Institute Common Terminology Criteria for Adverse Events version 5 grade ≥3) fluoropyrimidine-related toxicity across the entire treatment duration. Toxicity incidence between DPYD variant allele carriers and DPYD wild-type patients and poor or intermediate metabolizers and extensive metabolizers will be compared. | about 3 months |
| Secondary Outcome Measures | Measure Description | Time Frame |
|---|
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
|
Study Contact Name: An Lambaerts Phone Number: +3211338461 Email: an.lambaerts@jessazh.be |
Study Contact Backup Name: Liesbeth Decoutere Phone Number: +3211338411 Email: liesbeth.decoutere@jessazh.be |
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.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
