NeoplasmsPhase 1NCT00838370
Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines
A Phase 1 study testing Capecitabine, 5-fluorouracil in people with Neoplasms, run by The Netherlands Cancer Institute at 3 sites in Netherlands.
Trial summary
The primary purpose of this study is to prospectively determine whether capecitabine and 5-FU-induced toxicity is preventable by dose reduction prior to start of the first administration in patients heterozygous or homozygous mutant for DPYD*2A, and to determine whether this strategy is cost-effective. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Capecitabine, 5-fluorouracil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 3 sitesNetherlands
- Study dates
- May 2007to Oct 2011
- Phase
- Phase 1
- 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
- Histological proof of cancer
- patient is considered for treatment with capecitabine or 5-FU
- hetero- or homozygous mutant for DPYD*2A
- able and willing to give written informed consent
- able and willing to undergo blood sampling for pharmacokinetic analysis
- life expectancy 3 months or longer
Show all 9Show fewer
- acceptable safety laboratory values (ANC, platelet count, ASAT, ALAT, creatinine,
- WHO performance status 0-2
- no radio- or chemotherapy within the last 3 weeks prior to study entry
Who cannot join
- patients with known alcoholism, drug addiction and/or psychotic disorders that are not suitable for adequate follow-up
- women who are pregnant or breast-feeding
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, 1066CX
Slotervaart Hospital
Amsterdam, 1066
Canisius Wilhelmina Hospital
Nijmegen, 6532SZ
About this study
The primary purpose of this study is to prospectively determine whether capecitabine and 5-FU-induced toxicity is preventable by dose reduction prior to start of the first administration in patients heterozygous or homozygous mutant for DPYD*2A, and to determine whether this strategy is cost-effective. Secondly, an individualized treatment algorithm for capecitabine and 5-FU therapy in DPYD*2A mutant patients will be developed and the pharmacokinetic profile of capecitabine and 5-FU will be assessed.
Read the detailed description
Patients exhibiting a genetically determined disorder (DPYD*2A) in the metabolic degradation of the frequently used anticancer agents capecitabine and 5-FU (fluoropyrimidines) are at high risk of development of severe and life-threatening toxicity during standard treatment with these compounds. Treatment and recovery of this fluoropyrimidine-induced severe toxicity often requires prolonged periods of hospitalization.
Screening for DPYD*2A in patients to treat with fluoropyrimidine drugs with subsequent dose adjustments in mutant individuals prior to start of therapy will possibly reduce the number of severe toxicity events. Furthermore, by reducing the frequency and/or duration of hospitalization, substantial medical costs can be saved, making this a cost-effective strategy.
- Conditions
- Neoplasms
- Being tested
- Capecitabine, 5-fluorouracil
- Keywords
- Pharmacogenetics, cost-benefit analysis, toxicity, antineoplastic drugs, Dihydropyrimidine Dehydrogenase
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Capecitabine, 5-fluorouracilDrug
Also called Xeloda, Capecitabine, Fluorouracil, 5-Fluorouracil
Patients to treat with capecitabine/5-FU will be screened prior to start of therapy for DPYD*2A. Patients heterozygous or homozygous mutant for DPYD*2A receive dose reductions of capecitabine/5-FU of at least 50% in the first two courses. In case this dose is tolerated well, doses will be increased.
In addition, the pharmacokinetics of capecitabine/5-FU and their metabolites will be assessed in these patients.
| Study group | Role | What they receive |
|---|---|---|
| DPYD*2A | Experimental | Patients are screened for a DPD-deficiency. Patients with a DPYD*2A mutation are eligible for intervention with capecitabine/5-FU . Receives: Drug: Capecitabine, 5-fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety
Measured: during fluoropyrimidine treatment of the patient
Secondary outcomes (1)
cost-effectiveness
Measured: during fluoropyrimidine treatment of the patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2009 (estimated)
- Study startMay 2007
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Investigators
- Jan HM Schellens, MD, PhD, Principal investigator, Netherlands Cancer Institute, Amsterdam, the Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00838370
- Sponsor's protocol ID
- NKI-AVL_M07PFU
- Status last verified
- Mar 2014
- First submitted
- 5 Feb 2009
- Last updated
- 4 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Knikman JE, Lopez-Yurda M, Meulendijks D, Deenen MJ, Schellens JHM, Beijnen J, Cats A, Guchelaar HJ. A Nomogram to Predict Severe Toxicity in DPYD Wild-Type Patients Treated With Capecitabine-Based Anticancer Regimens. Clin Pharmacol Ther. 2024 Feb;115(2):269-277. doi: 10.1002/cpt.3100. Epub 2023 Nov 29.
PubMed 37957132Meulendijks D, van Hasselt JGC, Huitema ADR, van Tinteren H, Deenen MJ, Beijnen JH, Cats A, Schellens JHM. Renal function, body surface area, and age are associated with risk of early-onset fluoropyrimidine-associated toxicity in patients treated with capecitabine-based anticancer regimens in daily clinical care. Eur J Cancer. 2016 Feb;54:120-130. doi: 10.1016/j.ejca.2015.10.013. Epub 2016 Jan 4.
PubMed 26761784Deenen MJ, Meulendijks D, Cats A, Sechterberger MK, Severens JL, Boot H, Smits PH, Rosing H, Mandigers CM, Soesan M, Beijnen JH, Schellens JH. Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis. J Clin Oncol. 2016 Jan 20;34(3):227-34. doi: 10.1200/JCO.2015.63.1325. Epub 2015 Nov 16.
PubMed 26573078
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenomic and Pharmacokinetic Safety and Cost-saving Analysis in Patients Treated With Fluoropyrimidines
- ClinicalTrials.gov ID
- NCT00838370
- Acronym / sponsor ID
- NKI-AVL_M07PFU
- Conditions
- Neoplasms
- Keywords
- Pharmacogenetics, cost-benefit analysis, toxicity, antineoplastic drugs, Dihydropyrimidine Dehydrogenase
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Study start
- May 2007
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 6 Feb 2009 (estimated)
- 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 primary purpose of this study is to prospectively determine whether capecitabine and 5-FU-induced toxicity is preventable by dose reduction prior to start of the first administration in patients heterozygous or homozygous mutant for DPYD*2A, and to determine whether this strategy is cost-effective. Secondly, an individualized treatment algorithm for capecitabine and 5-FU therapy in DPYD*2A mutant patients will be developed and the pharmacokinetic profile of capecitabine and 5-FU will be assessed.
Detailed description
Patients exhibiting a genetically determined disorder (DPYD*2A) in the metabolic degradation of the frequently used anticancer agents capecitabine and 5-FU (fluoropyrimidines) are at high risk of development of severe and life-threatening toxicity during standard treatment with these compounds. Treatment and recovery of this fluoropyrimidine-induced severe toxicity often requires prolonged periods of hospitalization.
Screening for DPYD*2A in patients to treat with fluoropyrimidine drugs with subsequent dose adjustments in mutant individuals prior to start of therapy will possibly reduce the number of severe toxicity events. Furthermore, by reducing the frequency and/or duration of hospitalization, substantial medical costs can be saved, making this a cost-effective strategy.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DPYD*2A | Experimental | Drug: Capecitabine, 5-fluorouracilPatients are screened for a DPD-deficiency. Patients with a DPYD*2A mutation are eligible for intervention with capecitabine/5-FU . |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histological proof of cancer
- patient is considered for treatment with capecitabine or 5-FU
- hetero- or homozygous mutant for DPYD*2A
- able and willing to give written informed consent
- able and willing to undergo blood sampling for pharmacokinetic analysis
Key exclusion criteria (2 listed)
- patients with known alcoholism, drug addiction and/or psychotic disorders that are not suitable for adequate follow-up
- women who are pregnant or breast-feeding
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 |
|---|---|---|
| Capecitabine, 5-fluorouracilAlso: Xeloda, Capecitabine, Fluorouracil, 5-FluorouracilPatients to treat with capecitabine/5-FU will be screened prior to start of therapy for DPYD*2A. Patients heterozygous or homozygous mutant for DPYD*2A receive dose reductions of capecitabine/5-FU of at least 50% in the first two courses. In case this dose is tolerated well, doses will be increased. In addition, the pharmacokinetics of capecitabine/5-FU and their metabolites will be assessed in these patients. | Drug | DPYD*2A |
Primary outcome
safety
Time frame: during fluoropyrimidine treatment of the patient
1 secondary outcome
cost-effectiveness
Time frame: during fluoropyrimidine treatment of the patient
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2014.
- Derived from this study: PubMed 37957132Knikman JE, Lopez-Yurda M, Meulendijks D, Deenen MJ, Schellens JHM, Beijnen J, Cats A, Guchelaar HJ. A Nomogram to Predict Severe Toxicity in DPYD Wild-Type Patients Treated With Capecitabine-Based Anticancer Regimens. Clin Pharmacol Ther. 2024 Feb;115(2):269-277. doi: 10.1002/cpt.3100. Epub 2023 Nov 29.
- Derived from this study: PubMed 26761784Meulendijks D, van Hasselt JGC, Huitema ADR, van Tinteren H, Deenen MJ, Beijnen JH, Cats A, Schellens JHM. Renal function, body surface area, and age are associated with risk of early-onset fluoropyrimidine-associated toxicity in patients treated with capecitabine-based anticancer regimens in daily clinical care. Eur J Cancer. 2016 Feb;54:120-130. doi: 10.1016/j.ejca.2015.10.013. Epub 2016 Jan 4.
- Derived from this study: PubMed 26573078Deenen MJ, Meulendijks D, Cats A, Sechterberger MK, Severens JL, Boot H, Smits PH, Rosing H, Mandigers CM, Soesan M, Beijnen JH, Schellens JH. Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis. J Clin Oncol. 2016 Jan 20;34(3):227-34. doi: 10.1200/JCO.2015.63.1325. Epub 2015 Nov 16.
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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.
Jan HM Schellens, MD, PhD principal investigator
Netherlands Cancer Institute, Amsterdam, the Netherlands
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Capecitabine, 5-fluorouracil in people with Neoplasms, run by The Netherlands Cancer Institute at 3 sites in Netherlands.
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 9 inclusion and 2 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: finished, as of the sponsor's last update on 4 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety (time frame: during fluoropyrimidine treatment of the patient). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00838370, which also lists 3 linked publications.
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 4 Mar 2014.