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    The EU Clinical Trials Register currently displays   38003   clinical trials with a EudraCT protocol, of which   6235   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2012-005282-12
    Sponsor's Protocol Code Number:
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2013-06-03
    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 ConcernedUK - MHRA
    A.2EudraCT number2012-005282-12
    A.3Full title of the trial
    TOFFEE Trial
    Toxicity OF Fluoropyrimidines: A comparative study of the cardiotoxicity of capEcitabine and tEysuno
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Trial comparing the effects of two chemotherapy drugs on the heart
    A.3.2Name or abbreviated title of the trial where available
    TOFFEE Trial
    A.4.1Sponsor's protocol code number
    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 SponsorUniversity of Edinburgh
    B.1.3.4CountryUnited Kingdom
    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 supportNordic Pharma
    B.4.2CountryUnited Kingdom
    B.4.1Name of organisation providing supportBritish Heart Foundation
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity of Edinburgh
    B.5.2Functional name of contact point
    B.5.3 Address:
    B.5.3.1Street AddressAnnya Smyth
    B.5.3.2Town/ cityEdinburgh
    B.5.3.3Post codeEH16 4TJ
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01312423325
    B.5.5Fax number01312429447
    B.5.6E-mailAnnya.Smyth@ed.ac.uk
    B.Sponsor: 2
    B.1.1Name of SponsorResearch and Development NHS Lothian
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsor
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNordic Pharma
    B.4.2CountryUnited Kingdom
    B.4.1Name of organisation providing supportEdinburgh & Lothians Health Foundation
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 Tegafur / Gimeracil / Oteracil tablets
    D.2.1.1.2Name of the Marketing Authorisation holderNordic Group BV
    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 nameTeysuno
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTegafur (JP15/USAN/INN)
    D.3.9.1CAS number 82294-77-7
    D.3.9.2Current sponsor codeTF
    D.3.9.3Other descriptive name5-fluoro-1-(oxolan-2-yl)pyrimidine-2,4-dione
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number15 to 20
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNGimeracil
    D.3.9.1CAS number 103766-25-2
    D.3.9.2Current sponsor codeCDHP
    D.3.9.3Other descriptive nameTAB-1001
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number4.35 to 5.8
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOteracil
    D.3.9.1CAS number 2207-75-2
    D.3.9.2Current sponsor codeoxo
    D.3.9.3Other descriptive nameOteracil potassium, Potassium otastat, Oxonic acid potassium salt
    D.3.9.4EV Substance CodeAS3
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number11.8 to 15.8
    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 RoleComparator
    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 Xeloda
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameXeloda
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNcapecitabine
    D.3.9.1CAS number 154361-50-9
    D.3.9.3Other descriptive namexeloda
    D.3.9.4EV Substance CodeAS4
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number150 to 500
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    All gastrointestinal and hepatobiliary cancers including colorectal cancer, cancer of unknown primary, pancreatic cancer, stomach cancer and oesophageal cancer.
    E.1.1.1Medical condition in easily understood language
    Cancer of the bowel, stomach, gullet, pancreas and cancer of unknown primary site
    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
    Does teysuno cause less cardiotoxicity than capecitabine?
    E.2.2Secondary objectives of the trial
    Does the level of damage to the heart and blood vessels correlate with the level of toxic waste products from the study drug?
    Is the risk of developing heart damage greater in patients with pre-existing heart problems?
    Is the underlying mechanism that causes drug related heart damage due to an effect on the blood vessels or disruption of blood clotting?

    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Male or female patients at least 18 years or over with no upper age limit.
    • Confirmed advanced or metastatic oesophageal, gastric, gastro-oesophageal, small bowel, colorectal, cancer of unknown primary, hepatobiliary or pancreatic cancer.
    • Suitable for treatment with fluoropyrimidine, either alone or in combination with oxaliplatin.
    • WHO performance status (PS) 0, 1 or 2 and considered by responsible consultant to be fit to undergo planned chemotherapy and cardiac investigations.
    • Baseline laboratory tests (within 1 week prior to starting treatment):
    - Neutrophils >1.5 x109 /L and platelet count > 100 x109 /L
    - Serum bilirubin <1.5 x upper limit of normal (ULN), alkaline phosphatase <5x ULN, and serum transaminase (either AST or ALT) <3 x ULN
    - Estimated creatinine clearance (Cockcroft and Gault, adjusted for BSA>50 mL/min or estimated glomerular filtration rate (eGFR) or measured GFR (EDTA clearance) >30 mL/min. [Patients with Cr Cl 30-50 mL/min will be included but should be treated at a reduced dose (see master prescription chart)]
    • For women of childbearing potential, negative pregnancy test and adequate contraceptive precautions.
    • Effective contraception for male patients if the risk of conception exists.
    • Written informed consent for participation in the trial.
    E.4Principal exclusion criteria
    • Patients who are unfit for the chemotherapy regimens in this protocol, such as:
    - Severe uncontrolled concurrent medical illness (including poorly controlled angina or very recent MI, i.e. in previous 3 months) likely to interfere with protocol treatments
    - Any psychiatric or neurological condition which is felt likely to compromise the patient's ability to give informed consent or to comply with oral medication
    - Partial or complete bowel obstruction
    - Pre-existing neuropathy > grade 1 if combination therapy proposed DELETED
    • Patients on therapeutic anticoagulation (warfarin or LMWH).
    • Patients unable to lie flat. DELETED
    • Patients unable to withstand the visits and cardiovascular investigations proposed within the study.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of the study will be a difference in the duration of ST deviation pre-treatment and during treatment. This will be recorded using Del Mar Reynolds Lifecard CF/Lifecard 12 recorders, which will record 12 leads over 24 hours and continuously if the storage card is changed daily. Pre-treatment control ECGs will be recorded for 24 hours. Continuous 12-lead monitoring shall be recorded for 3 days between day 5 and day 7. Data will be analysed on a Pathfinder Digital Analyser. All analyses will be carried out by a blinded observer. The electrocardiogram will be visually inspected for quality and if satisfactory will be analysed using the automated algorithms within the software package. The baseline ST segment deviation will be determined as the average of the entire 24-hour period, and will be set for each lead (II, V2 and V5 –representative of the inferior, anterior and lateral walls of the heart respectively) separately. After the baseline is set, the automated algorithm will determine episodes of ST deviation that meet the criteria and will subsequently be recorded. Number and duration of ST changes will be reported. Ischemic episodes are defined as > 1 mm (0.1 mV) ST deviation, measured at the J-point + 80ms and lasting > 60 seconds. The co-investigators have experience with this technique, which has been used to detect cardiac ischaemia induced by diesel pollution.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The study participants will be monitored continuously by ECG for 3 days (preferably days 5-7, but may be performed at any point between days 3-10).
    E.5.2Secondary end point(s)
    Does the level of damage to the heart and blood vessels correlate with the level of toxic waste products from the study drug?
    Is the risk of developing heart damage greater in patients with pre-existing heart problems?
    The underlying mechanism that causes drug related heart damage due to damage of the blood vessels or disruption of blood clotting?
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary endpoints will be measured at baseline and after 7, 14 and 21 days of taking the study drug
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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 Yes
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state60
    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)
    Patients will either revert to normal standard chemotherapy (capecitabine based) or be able to continue with the study drug after the end of the trial at the discretion of the patient's oncologist. The oncologist and patient will be aware of which treatment the patient had been randomised to during the study, on completion of their study visits, to help with these decisions. The cardiovascular research team will remain blinded to this information.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-05-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-01-08
    P. End of Trial
    P.End of Trial StatusOngoing
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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