Pharmacological study of chronomodulated capecitabine therapy
Recruiting
- Conditions
- cancer, capecitabine, phase I, chronotherapy, biomarker, pharmacology, kanker, chronotherapie, fase I
- Registration Number
- NL-OMON24089
- Lead Sponsor
- etherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 42
Inclusion Criteria
1. Histological or cytological proof of cancer
2. Patient who might benefit from treatment with capecitabine, e.g. colon, breast, pancreatic and gastric cancer, ACUP;
Exclusion Criteria
1. Dihydropyrimidine dehydrogenase (DPD) deficiency as assessed on the basis of DPYD IVS14+1G>A (DPYD*2A) and 2846A>T mutation analysis;
2. Women who are pregnant or breast feeding;
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs) and recommended dose (RD) of continuous and intermittent chronomodulated capecitabine.
- Secondary Outcome Measures
Name Time Method The plasma pharmacokinetics of capecitabine and its metabolites 5-dFCR, 5-dFUR, 5-FU and FBAL;<br /><br>The inter- and intra-patient variability in plasma pharmacokinetics;<br /><br>Baseline and circadian dihydropyrimidine dehydrogenase (DPD) activity in peripheral blood mononuclear cells (PBMCs) and<br>in plasma by means of the dihydrouracil (UH2) / uracil (U) ratio;<br /><br>Baseline and circadian thymidylate synthase (TS) activity in PBMCs;<br /><br>Baseline thymidine phosphorylase (TP) activity in PBMCs;<br /><br>The description of pharmacokinetic/pharmacodynamic (PK/PD) relationships;<br /><br>The preliminary antitumor activity of chronomodulated capecitabine;<br /><br>Associations of polymorphisms in DPYD or TYMS with DPD or TS enzyme activity in PBMCs and clinical response;<br /><br>Intracellular pharmacokinetics of 5-FU nucleotides in PBMCs.