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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   42556   clinical trials with a EudraCT protocol, of which   7007   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
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    Summary
    EudraCT Number:2014-005064-15
    Sponsor's Protocol Code Number:M14DPD
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-12-18
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2014-005064-15
    A.3Full title of the trial
    Safety, feasibility and cost-effectiveness of genotype-directed individualized dosing of fluoropyrimidines
    Veiligheid, haalbaarheid en kosten-effectiviteit van geïndividualiseerd doseren op basis van genotypering bij fluoropyrimidines
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study about adjusting the dose of the anticancer drugs fluoropyrimindes based on mutations in DNA (genetic code)
    Een onderzoek naar het aanpassen van de dosis van de antikankergeneesmiddelen fluoropyrimidines op basis van afwijkingen in het DNA (erfelijk materiaal)
    A.3.2Name or abbreviated title of the trial where available
    Genotype-directed individualized dosing of fluoropyrimidines
    Geïndividualiseerd doseren op basis van genotypering bij fluoropyrimidines
    A.4.1Sponsor's protocol code numberM14DPD
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNetherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI-ALV)
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAlpe d'HuZes/KWF Grant
    B.4.2CountryNetherlands
    B.4.1Name of organisation providing supportCambridge Isotope Laboratories Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNetherlands Cancer Institute
    B.5.2Functional name of contact pointJan Schellens
    B.5.3 Address:
    B.5.3.1Street AddressPlesmanlaan 121
    B.5.3.2Town/ cityAmsterdam
    B.5.3.3Post code1066 CX
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+310205122446
    B.5.5Fax number+310205122572
    B.5.6E-mailj.schellens@nki.nl
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Capecitabine
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCapecitabine
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name fluorouracil
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namefluorouracil
    D.3.4Pharmaceutical form Concentrate for solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Types of cancer for which capecitabine and 5-fluorouracil are authorized, this includes colorectal cancer, gastric cancer and locally advanced or metastatic breast cancer
    Types kanker waarvoor capecitabine en 5-fluorouracil zijn geregistreerd, dit omvat colorectaalcarcinoom, maagcarcinoom, lokaal voortgeschreden of gemetastaseerd mammacarcinoom.
    E.1.1.1Medical condition in easily understood language
    Cancer for which the medicines capecitabine and 5-fluorouracil are used. This includes colorectal cancer, gastric cancer and breast cancer.
    Kanker waarvoor de geneesmiddelen capecitabine en 5-fluorouracil worden gebruikt. Dit omvat darmkanker, maagkanker en borstkanker.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine whether the rate of severe toxicity (grade 3 to 5, grading according to CTC-AE version 4.03) associated with fluoropyrimidine treatment can be significantly diminished by individualized dosing of fluoropyrimidines based on upfront genotypic assessment of DPD deficiency.
    E.2.2Secondary objectives of the trial
    To determine whether individualized dosing based on upfront genotypic assessment of DPD deficiency is cost-effective.

    To determine the additional value of an array-based screening of additional decreased activity DPYD-alleles, by determining associations between these variants and occurrence of severe fluoropyrimidine-induced toxicity.

    To assess the pharmacokinetic profile of capecitabine and 5-FU in DPD deficient patients (e.g. patients carrying variant DPYD alleles) given reduced dosages of the respective drugs.

    To determine the clinical sensitivity, specificity, positive predictive value and negative predictive value of phenotype-based screening using the endogenous DHU/U ratio, uracil breath test and uracil test dose.

    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Pathologically confirmed malignancy for which treatment with a fluoropyrimidine is considered to be in the patient’s best interest
    2. Age  18 years
    3. Able and willing to give written informed consent
    4. WHO performance status of 0, 1 or 2
    5. Life expectancy of at least 12 weeks
    6. Able to swallow and retain oral medication
    7. Able and willing to undergo blood sampling for pharmacogenetic and phenotyping analysis
    8. Minimal acceptable safety laboratory values
    a. ANC of  1.5 x 109 /L
    b. Platelet count of  100 x 109 /L
    c. Hepatic function as defined by serum bilirubin  1.5 x ULN, ALAT and ASAT  2.5 x ULN; in case of liver metastases ALAT and ASAT  5 x ULN.
    d. Renal function as defined by serum creatinine  1.5 x ULN or creatinine clearance  60 ml/min (by Cockcroft-Gault formula).
    E.4Principal exclusion criteria
    1. Prior treatment with fluoropyrimidines
    2. Patients with known substance abuse, psychotic disorders, and/or other diseases expected to interfere with study or the patient’s safety
    3. Women who are pregnant or breast feeding
    4. Both men and women who refuse to use reliable contraceptive methods throughout the study (adequate contraceptive methods are: condom, sterilization, other barrier contraceptive measures preferably in combination with condoms)
    5. Patients with a homozygous polymorphic genotype or compound heterozygous genotype for DPYD.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint in this study is the incidence of severe treatment-related toxicity (CTC grade 3 to 5) in patients carrying DPYD variants compared to wild type patients and compared to a historical cohort of DPYD heterozygous patients treated with a full dose of fluoropyrimidines.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At the end of the trial
    E.5.2Secondary end point(s)
    Secondary endpoints are: cost-effectiveness, assessment of pharmacokinetics and DPD enzyme activity.
    E.5.2.1Timepoint(s) of evaluation of this end point
    At the end of the trial
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy No
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence Yes
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned10
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of trial is defined as the date of the last visit of the last patient enrolled in the trial. The analysis time point is defined as all enrolled patients that have undergone the 30 day post safety follow up.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 650
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 600
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state1250
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Further treatment is determined in the best interest of the patient in
    consultation with the treating physician.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-12-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-02-12
    P. End of Trial
    P.End of Trial StatusCompleted
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