Colon CancerPhase 4NCT04269369
Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
A Phase 4 study testing 5-Fluorouracil in people with Colon Cancer and Stomach Tumor, run by Jessa Hospital.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colon Cancer, Stomach Tumor, Anal Tumor
- What is being tested?
- 5-Fluorouracil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- No sites listed yet
- Study dates
- 18 Feb 2020to 30 Sep 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 18 years or older
- WHO (world health organization) classification 0,1 or 2
- A suspected start with 5-FU or capecitabine in mono or combination therapy
- The knowledge of the result of the geno and phenotyping before the start of the treatment
Who cannot join
- Not meeting inclusion criteria
- Homozygote genotype or uracil 100 ng/ml or greater
- The lacking of the result of the geno and / or phenotyping before the start of treatment
- Patients who received 5-FU or capecitabine in the past
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients With the Aim of Reducing Toxicity
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.
Read the detailed description
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.
- Conditions
- Colon Cancer, Stomach Tumor, Anal Tumor, Pancreas Cancer, Esophageal Cancer
- Being tested
- 5-Fluorouracil
- Medical subject headings
- Colonic Neoplasms, Stomach Neoplasms, Anus Neoplasms, Pancreatic Neoplasms, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FluorouracilDrug
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 dosing table was obtained by combining the results of the study by Henricks et al., Launay et al. and Yang et al. and the recommendations from the French HAS guideline. The treatment schedule then will be discussed by the team of doctors and paramedics at the weekly MOC (multidisciplinary cancer consultation). Complementary, the pharmacist provides dose advice with regard to the start of 5-FU or capecitabine treatment.
In a subgroup, the group of patients with genotype "wild type" and phenotype "intermediate metabolizer", a comparison will be made between group A with dosage according to French guidelines and group B with dosage according to literature.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Dosage according to French guidelines Receives: Drug: 5-Fluorouracil |
| Group B | Experimental | Dosage according to literature Receives: Drug: 5-Fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: about 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2020
- Study start18 Feb 2020 (estimated)
- Primary completion30 Sep 2021 (estimated)
- Study completion30 Sep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colon CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In a subgroup of patients, a parallel study model will be used. In the group of patients with genotype "wild type" and phenotype "intermediate metabolizer", a comparison will be made between group A with dosage according to French guidelines and group B with dosage according to literature. After obtaining written informed consent, patients will be randomized in a 1:1 ratio to one of the two study groups.
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jessa Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- An Lambaerts, Principal investigator, Jessa Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04269369
- Sponsor's protocol ID
- FluorouracilCapecitabine001
- Status last verified
- Feb 2020
- First submitted
- 11 Feb 2020
- Last updated
- 13 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients With the Aim of Reducing Toxicity
- ClinicalTrials.gov ID
- NCT04269369
- Acronym / sponsor ID
- FluorouracilCapecitabine001
- Conditions
- Colon Cancer, Stomach Tumor, Anal Tumor, Pancreas Cancer, Esophageal Cancer
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Jessa HospitalUniversity, hospital or other
- Study start
- 18 Feb 2020 (estimated)
- Primary completion
- 30 Sep 2021 (estimated)
- Study completion
- 30 Sep 2021 (estimated)
- First posted
- 13 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- In a subgroup of patients, a parallel study model will be used. In the group of patients with genotype "wild type" and phenotype "intermediate metabolizer", a comparison will be made between group A with dosage according to French guidelines and group B with dosage according to literature. After obtaining written informed consent, patients will be randomized in a 1:1 ratio to one of the two study groups.
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: 5-FluorouracilDosage according to French guidelines |
| Group B | Experimental | Drug: 5-FluorouracilDosage according to literature |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients aged 18 years or older
- WHO (world health organization) classification 0,1 or 2
- A suspected start with 5-FU or capecitabine in mono or combination therapy
- The knowledge of the result of the geno and phenotyping before the start of the treatment
Key exclusion criteria (4 listed)
- Not meeting inclusion criteria
- Homozygote genotype or uracil 100 ng/ml or greater
- The lacking of the result of the geno and / or phenotyping before the start of treatment
- Patients who received 5-FU or capecitabine in the past
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-FluorouracilThe 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 dosing table was obtained by combining the results of the study by Henricks et al., Launay et al. and Yang et al. and the recommendations from the French HAS guideline. The treatment schedule then will be discussed by the team of doctors and paramedics at the weekly MOC (multidisciplinary cancer consultation). Complementary, the pharmacist provides dose advice with regard to the start of 5-FU or capecitabine treatment. In a subgroup, the group of patients with genotype "wild type" and phenotype "intermediate metabolizer", a comparison will be made between group A with dosage according to French guidelines and group B with dosage according to literature. | Drug | Group A, Group B |
Primary outcome
The frequency of severe fluoropyrimidine-related toxicity
Time frame: about 3 months
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
An Lambaerts principal investigator
Jessa Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 5-Fluorouracil in people with Colon Cancer and Stomach Tumor, run by Jessa Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact An Lambaerts (+3211338461, an.lambaerts@jessazh.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The frequency of severe fluoropyrimidine-related toxicity (time frame: about 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2020.