A combination of pre-screening for DPD deficiency by genotyping/phenotyping methods and pharmacokinetics-guided dosing of 5-FU for precision treatment to prevent severe toxicity in gastrointestinal cancer patients.
- Conditions
- 10017991DPD deficiency
- Registration Number
- NL-OMON52496
- Lead Sponsor
- Isala Klinieken
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 75
• age 18 years and older
• histological proof of gastro-intestinal cancer
• patient is considered for treatment with capecitabine or 5-FU
• acceptable safety laboratory values
• ECOG performance status 0-2
• able and willing to give written informed consent
• able and willing to undergo blood sampling for DPYD genotyping, DPD
phenotyping and pharmacokinetic analysis
• symptomatic or uncontrolled central nervous system metastases
• patient who cannot submit itself to the formal follow-up for psychological,
social, family or geographical reasons
• women who are pregnant or breast-feeding
• women not consenting to use adequate contraceptive precautions during the
study
• significant serious pathology or any instable medical condition (cardiac
pathology uncontrolled, myocardial infarction within 6 months before enrolment,
systemic active uncontrolled infection, cirrhosis (Child-Pugh score C), renal
failure (GFR < 20 ml/min))
• any investigational agent within 4 weeks before enrolment
• cimetidine or sorivudine use (due to drug-drug interactions with
5-fluorouracil and capecitabine)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary outcome of the study is the clearance of 5-FU at steady state<br /><br>(Clss) measured in ml/min. Among cancer patients treated with 5-FU, we will<br /><br>compare the variation in clearance between the four common DPYD variant allele<br /><br>carriers and DPYD wild-type carriers. </p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary study parameters are the incidence of 5-FU related toxicities,<br /><br>U/DHU ratio, DPD phenotype (EM, IM, and PM), 5-FU doses, dosage adjustment and<br /><br>time to reach target AUC (cycle number).</p><br>