Sponsor study identifier
interventional
37
1 country
2
Study Start
October 2012
Date type not reportedThis date has not been verified as actual or estimated.
Primary Completion
November 2015
Actual (reported)Study Completion
November 2015
Actual (reported)The fluoropyrimidines 5-fluorouracil (5FU) and capecitabine (Cp) are among the most commonly used anticancer drugs. Still, there is much controversy about the correct dosing, and the fact that a minority of patients experience severe, sometimes even lethal toxicity following treatment. One important factor predisposing patients to severe toxicity is deficiency in the 5FU-catabolic enzyme dihydropyrimidine dehydrogenase (DPD). Our group identified 4 DPD risk alleles in over 300 Swiss cancer patients, that resulted in a 8-times increased risk of experiencing severe toxicity from 5FU or Cp. In patients receiving 5FU as a continuous infusion, there are accumulating data that keeping the AUC of 5FU between 20-30 mg\*h/L is beneficial in terms of treatment toxicity and activity. In this study, patients carrying at least 1/4 DPD risk alleles will receive a 50% dose reduction of either 5FU or Cp, with the potential of later dose increases in the abscence of severe toxicity. Additionally, patients receiving i.v. 5FU will undergo therapeutic drug monitoring at the end of the 2-day continuous infusion, with subsequent dose adaptations to target a 5FU AUC of 20-30 mg\*h/L. The primary study objective is to reduce the incidence of severe treatment-related toxicity from 13% (in historical controls) to 5% in study patients.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
November 2015
Actual (reported)Click on a node to explore related trials.
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Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
July 11, 2012
Actual (reported)July 16, 2012
Actual (reported)October 2012
Date type not reportedThis date has not been verified as actual or estimated.
November 2015
Actual (reported)November 2015
Actual (reported)Predefined fluoropyrimidine-related (index) toxicity
Index toxicity is defined as follows: * All adverse events CTC grades ≥3, including myelosuppression but excluding nausea and vomiting (that is often due to concurrent platinum drug treatment) * Fluoropyrimidine-related toxicity CTC grade ≥2, including mucositis, dehydration, hand-foot syndrome * Diarrhea CTC grade ≥2 lasting for \>/=5 days or an increase of 2 CTC grades in case of preexisting diarrhea. Diarrhea should not be evaluated in patients with a colostomy
After 6 weeks of fluoropyrimidine-based treatment
Area-under-the plasma-concentration time curve of 5-fluorouracil
at 8 weeks
Endogenous dihydrouracil/uracil ratio in plasma
at start of each treatment cycle
Objective treatment response (best response) according to RECIST v.1.1
end of first-line treatment
Progression-free survival
time of disease progression or death
DPYD-genotype and TDM-driven dosing of 5FU/Capecitabine
Multiplex amplification of each sample is performed in an individual well of a 24-well plate using a Mastercycler platform. Template and Platinum Taq Polymerase (Life Technologies, Carlsbad, California) are added to an analyte-specific amplification mix (AutoGenomics Inc., Carlsbad, California). After amplification, the plate is transferred into the Infinity analyzer (AutoGenomics Inc.), followed by primer extension and hybridization of detection primers to individual oligonucleotides arrayed on the Bio-FilmChip. After hybridization, the BioFilmChips are washed and scanned in the Infiniti optics module. The Autogenomics DPYD assay is used to detect the presence of the four risk alleles (IVS14+G\>A, c.1679T\>G, HapB3/c.1129-5923C\>G and c.2846A\>T).
Inselspital
Bern, 3010, Switzerland
Cantonal Hospital
Sankt Gallen, 9007, Switzerland
Markus Joerger, MD PhD
Cantonal Hospital of St. Gallen
37 participants (actual enrollment reported by the registry).
First Submitted
July 11, 2012
First Posted
July 16, 2012
Study Start
October 2012
Date type not reportedThis date has not been verified as actual or estimated.
Repeated PK plasma sampling is done in all patients receiving 5FU. Blood is taken from venipuncture into one 5 ml heparin tube and into one 3 ml EDTA tube for the analysis of 5FU steady-state plasma concentrations in every (2-weekly) treatment cycle. Special attention has to be paid not to take PK blood from the site of drug infusion. For 5FU, PK sampling is done two hours before the calculated end of the 5FU pump on day 3 of every treatment cycle. The quantitative 5FU exposure expressed as the area-under-the concentration-time curve in mg•h/L is calculated from the measured steady-state plasma concentrations of 5FU and the duration of 5FU infusion. In all patients, 5FU doses for the second and subsequent administrations are adjusted to target a 5FU AUC between 20 and 30 mg•h/L
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Primary Completion
November 2015
Actual (reported)Study Completion
November 2015
Actual (reported)Last Updated
February 2, 2016
Record last verified: 2016-01
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Source: ClinicalTrials.gov.
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