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    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   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).

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    Summary
    EudraCT Number:2009-010140-33
    Sponsor's Protocol Code Number:SPON672-09
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2009-09-24
    Trial results View 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 number2009-010140-33
    A.3Full title of the trial
    A randomised phase II Trial of carboplatin and gemcitabine +/- vandetanib in first line treatment Of advanced Urothelial cell Cancer in patients who are not suitable to receive cisplatin

    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A trial of carboplatin and gemcitabine +/- vandetanib to treat patients with advanced bladder cancer who can't be treated with cisplatin
    A.3.2Name or abbreviated title of the trial where available
    Vandetanib in non-cisplatin fit patients with urothelial cancers
    A.4.1Sponsor's protocol code numberSPON672-09
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberISRCTN68146831
    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 SponsorCardiff University
    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 supportCancer Research UK
    B.4.2CountryUnited Kingdom
    B.4.1Name of organisation providing supportPfizer Ltd.
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationWales Cancer Trials Unit
    B.5.2Functional name of contact pointTracie Madden
    B.5.3 Address:
    B.5.3.1Street Address6th Floor Neuadd Meirionnydd, School of Medicine, Cardiff University, Heath Park
    B.5.3.2Town/ cityCardiff
    B.5.3.3Post codeCF14 4YS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02920687953
    B.5.5Fax number02920687500
    B.5.6E-mailMaddenTA1@cf.ac.uk
    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 No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/05/344
    D.3 Description of the IMP
    D.3.1Product nameZactima
    D.3.2Product code ZD6474
    D.3.4Pharmaceutical form 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 INNVandetanib
    D.3.9.1CAS number 443913-73-3
    D.3.9.2Current sponsor codeSPON672-09
    D.3.9.3Other descriptive nameN-(4-bromo-2-fluorophenyl)-6-methoxy-7-7[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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
    D.8.3Pharmaceutical form of the placeboCoated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Transitional cell carcinoma of urothelium (upper or lower urinary tract). Cancers with other pathologies are permitted, provided that the dominant morphology is transitional cell carcinoma.
    E.1.1.1Medical condition in easily understood language
    Advanced bladder cancer
    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
    The main objective of this trial is to assess whether the addition of vandetanib to standard carboplatin/gemcitabine cancer chemotherapy improves the clinical outcome for participants with advanced cancer of the urinary system (urothelial cancer).
    E.2.2Secondary objectives of the trial
    The secondary objective of this trial is to determine if the 3-drug chemotherapy combination of vandetanib, carboplatin and gemcitabine is safe and tolerable in participants with advanced cancer of the urinary system (urothelial cancer).
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Participants will be asked to participate in an optional sub-study of the main TOUCAN trial (see full title provided in Section A.3 of this form) and detailed in Section 13.0 Translational research of the trial protocol supplied with this application (Version Number 1.0, 10th August 2009). All TOUCAN participants will be asked to consider the provision of additional blood and urine samples for translational research. A separate research proposal will be submitted to fund analysis of collected samples. These samples will be collected pre- and post-treatment at baseline and at week 26. Permission will also be sought to analyse paraffin tissue blocks of previous tumour tissue specimens (e.g. from prior TURBT and/or cystectomy/nephro-ureterectomy). The objective of the sub-study is to analyse these samples to gain a better understanding of the 3-drug gemcitabine/carboplatin/vandetanib treatment in urothelial cancer.
    E.3Principal inclusion criteria
    Patients meeting all of the following criteria may be included in the trial:
    1. Male or female
    2. Age greater than or equal to 18 years
    3. Histologically confirmed transitional cell carcinoma (pure or mixed histology) of urothelium (upper or lower urinary tract). Cancers with other pathologies are permitted, provided that the dominant morphology is transitional cell carcinoma.
    4. Radiologically measurable (RECIST 1.1), locally advanced/and/or metastatic disease not amenable to curative treatment with surgery or radiotherapy not suitable for cisplatin, defined as one or more of the following:
    a) Creatinine clearance <60ml/min estimated by Cockcroft and Gault formula or measured by 24-hour urine collection or isotope clearance (N.B. patients are excluded if creatinine clearance is <30ml/min)
    b) ECOG Performance Status 2 (note patients are excluded if PS is 3 or worse)
    c) Clinically significant ischemic heart disease (MI or unstable angina 3-12 months prior to date of randomisation, or symptomatic angina, New York Heart Association Class I, 0-3 months prior to date of randomisation). See section 4 of exclusion criteria.
    d) Prior intolerance of cisplatin
    e) Age greater than 75
    f) Any other factor, which, in the opinion of the investigator indicates that cisplatin is not suitable for this patient (e.g. unilateral hearing loss)
    5. The patient has provided written informed consent.
    E.4Principal exclusion criteria
    If any of the following criteria apply, patients cannot be included in the trial:
    1. Laboratory results rendering patient unsuitable for trial treatment:
    a) Serum bilirubin >1.5x the upper limit of reference range (ULRR)
    b) Creatinine clearance < 30 mL/minute (calculated by Cockcroft-Gault formula or measured by 24-hour urine collection or isotope clearance).
    c) Potassium, <4.0 mmol/L despite supplementation; or above the CTCAE grade 1 upper limit
    d) Magnesium below the normal range despite supplementation, or above the CTCAE grade 1 upper limit
    e) Serum calcium above the CTCAE grade 1 upper limit. In cases where the serum calcium is below the normal range, the calcium adjusted for albumin is to be obtained and substituted for the measured serum value. Exclusion is to then be based on the adjusted for albumin values falling below the normal limit.
    f) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULRR or alkaline phosphatase (ALP) >2.5 x ULRR, or > 5x ULRR if judged by the investigator to be related to liver metastases
    2. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
    3. ECOG performance status ≥ 3.
    4. Significant risk of cardiac complications defined as any of the following:
    a) Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena cava syndrome (SVC), New York Heart Association (NYHA) classification of heart disease >2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the investigator, significantly increases the risk of ventricular arrhythmia (N.B. this is complementary to inclusion criterion 4 (above)).
    b) History of arrhythmia (multifocal premature ventricular contractions PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not exclusionary
    5. QTc prolongation with other medications that required discontinuation of that medication
    6. Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age
    7. Presence of left bundle branch block (LBBB)
    8. QTc that is unmeasurable or > 480 msec on screening ECG. (Note: If a subject has a QTc interval >480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be <480 msec in order for the subject to be eligible for the study.) Patients who are receiving a drug that has a risk of Torsades de Pointes are excluded if QTc is ≥ 460 msec. Note: the method for estimating QTc must be consistent between all time points for any individual patient.
    9. Concomitant medication which has known adverse interaction with vandetanib, including:
    a) Any medication that may induce Torsades de Pointes (TdP). Note some medications that induce TdP may be continued with additional ECG monitoring if there is no suitable alternative, these are listed in the trial protocol.
    b) Potent inducers of CYP3A4 function (e.g. rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John’s Wort).
    10. Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
    11. Currently active diarrhea that may affect the ability of the patient to absorb the vandetanib or tolerate diarrhea
    12. Women who are currently pregnant or breast feeding. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to the start of trial therapy)
    13. Women or partners of women of child-bearing age who are not prepared to practice method(s) of birth control of established efficacy
    14. Previous or current malignancies of other histology within the last 5 years, with the exception of cervical carcinoma in situ, adequately treated basal or squamous cell carcinoma of the skin, or prostate cancer
    15. Receipt of any investigational agents within 30 days prior to commencing study treatment
    16. Major surgery within 4 weeks before starting study therapy or incompletely healed surgical wounds.
    17. Prior chemotherapy (unless delivered perioperatively and completed > 12 months prior to first presentation of recurrent disease)

    E.5 End points
    E.5.1Primary end point(s)
    Progression-Free Survival (PFS). Progression is defined according to RECIST 1.1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Six months after the last patient has been recruited into the study.
    E.5.2Secondary end point(s)
    Tolerability (side effects) and feasibility of use (number of participants requiring dose delays or reductions and/or treatment withdrawal). Objective response rate as assessed by RECISTv1.1. Overall survival (OS). Time from enrolment to death. Those still alive will be censored at time last seen. Change of sum of measurable lesions 9 weeks after start of chemotherapy (using Waterfall plots) (measurements according to RECIST v1.1). Toxicity, during and after treatment using NCI CTCAE v4.0. SAEs will be collected in real time.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Six months after the last patient has been recruited into the study.
    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 Yes
    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 Yes
    E.6.13.1Other scope of the trial description
    translational research
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    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 Yes
    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 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 concerned20
    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
    For the purposes of the MHRA and MREC, the end of trial is deemed to be the date of last data capture.
    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 months6
    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 Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 82
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 82
    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 Information not present in EudraCT
    F.4 Planned number of subjects to be included
    F.4.1In the member state82
    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)
    The gemcitabine/carboplatin 2-drug chemotherapy for this disease state is given for an 18 week period only. The 3-drug gemcitabine/carboplatin/vandetanib trial treatment will be given for an 18 week period only. Further vandetanib treatment will not be available after the 18 week trial treatment period. Once the participant has completed the trial treatment, any other treatment outside of the trial will be at the discretion of the local research doctor.
    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 Decision2009-11-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-09-04
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-09-05
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