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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   43724   clinical trials with a EudraCT protocol, of which   7255   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
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    EudraCT Number:2005-005077-29
    Sponsor's Protocol Code Number:D4200C00058
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-03-22
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2005-005077-29
    A.3Full title of the trial
    An International, Phase II, Randomized, Double-Blinded, Placebo- Controlled, Multi-Center Study to Assess the Efficacy of ZD6474 ZACTIMA versus Placebo in Subjects with Unresectable Locally Advanced or Metastatic Medullary Thyroid Cancer
    A.3.2Name or abbreviated title of the trial where available
    ZACTIMA 58
    A.4.1Sponsor's protocol code numberD4200C00058
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberND
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorASTRAZENECA
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    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 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/3/05/334
    D.3 Description of the IMP
    D.3.1Product nameZD6474/Vandetanib
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNOther antineoplastic agents
    D.3.9.1CAS number 338992-00-0
    D.3.9.2Current sponsor codeZD6474
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    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) Information not present in EudraCT
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product Information not present in EudraCT
    D. ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D. on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    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 placeboFilm-coated 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
    Unresectable Locally Advanced or Metastatic Medullary Thyroid Cancer
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 6.1
    E.1.2Level PT
    E.1.2Classification code 10027105
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate an improvement in progression-free survival PFS with ZD6474 as compared to placebo in subjects with unresectable locally advanced or metastatic MTC
    E.2.2Secondary objectives of the trial
    1.To demonstrate an improvement in the overall objective response rate ORR , disease control rate DCR , and duration of response DOR with ZD6474 as compared to placebo 2. To demonstrate an improvement in the overall survival OS in subjects with MTC who have been treated with ZD6474 as compared to placebo 3. To demonstrate an improvement in biochemical response with ZD6474 as compared to placebo as measured by calcitonin CTN and carcinoembryonic antigen CEA 4. To demonstrate an increase in the time to opioid analgesic use TTOU in subjects who are not taking opioid analgesics at baseline, defined as 10 mg morphine sulfate or equivalent , with ZD6474 as compared to placebo 5. To demonstrate a reduction in the use of opioid analgesic medication in subjects with MTC who have pain at baseline requiring 8805;10mg/day morphine sulfate or equivalent after treatment with ZD6474 as compared to placebo etc
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    1.Provision of written informed consent 2.Female or male aged 18 years and over 3. Previously confirmed histological diagnosis of unresectable, locally advanced or metastatic hereditary or sporadic MTC. Documentation must be provided in subject s medical chart. 4. Life expectancy of 12 weeks or longer 5. WHO Performance status 0-2 6. Able to swallow study medication 7. Presence of a measurable tumor as defined by a a solitary lesion measuring 8805;2 cm, OR b for multiple lesions, a sum of diameter 8805;2cm with no target lesion measuring 1cm and assuming 5 mm section , OR c for multiple lesions, a sum of diameter 8805;3cm with no target lesion measuring 1.5 cm assuming 5 mm section 8. CTN 8805; 500 pg/ml 9. All subjects other than those with hereditary MTC who have a documented germline RET mutation must submit a suitable archived tumor collection sample. If an archived tumor sample is not available prior to 2 weeks of randomization, a fresh tumor sample must be obtained in its place. The tumor sample must be obtained by the investigative site and shipped to its destination prior to randomization. 10. Negative pregnancy test for female subjects of childbearing potential
    E.4Principal exclusion criteria
    1. Brain metastases or spinal cord compression, unless treated at least 4 weeks before first dose and stable without steroid treatment for 10 days 2. Any concomitant medications that may affect QTc or induce CYP3A4 function with the exception of somatostatin or somatostatin analog and/or any prohibited medications referenced in Appendix E or Section 3.8 . 3. Major surgery within 4 weeks before randomization 4. The last dose of prior chemotherapy is received less than 4 weeks prior to randomization 5. Radiation therapy within the last 4 weeks prior to randomization with the exception of palliative radiotherapy 6. Serum bilirubin greater than 1.5 x the upper limit of reference range ULRR 7. Serum creatinine 1.5 x ULRR or creatinine clearance 8804;50 ml/minute calculated by Cockcroft-Gault formula 8. Potassium 4.0 mmol/L despite supplementation; serum calcium ionized or adjusted for albumin , or magnesium out of normal range despite supplementation 9. Alanine aminotransferase ALT , aspartate aminotransferase AST , or alkaline phosphatase ALP greater than 2.5 ULRR, or greater than 5.0 ULRR if judged by the investigator to be related to liver metastases 10. Significant cardiac event eg myocardial infarction , superior vena cava SVC syndrome, New York Heart Association NYHA classification of heart disease 8805;2 within 12 weeks before randomization, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia 11. History of arrhythmia multifocal premature ventricular contractions PVCs , bigeminy, trigeminy, ventricular tachycardia , which is symptomatic or requires treatment CTCAE grade 3 , symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted. 12. Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age 13. QT prolongation with other medications that required discontinuation of that medication 14. Presence of left bundle branch block LBBB 15. QTc with Bazett s correction unmeasurable or 8805;480 msec or greater on screening ECG Note If a subject has QTc interval 8805;480 msec on screening ECG, the screening ECG may be repeated 2 times at least 24 hours apart for a total of 3 ECGs. The average QTc from the three screening ECGs must be 480 msec in order for the subject to be eligible for the study. 16. Hypertension not controlled by medical therapy systolic BP greater than 160 millimeter of mercury mmHg or diastolic blood pressure greater than 100 mmHg 17. Previous or current malignancies of other histologies within the last 5 years, with the exception of tumors associated with MEN2a and MEN2b, in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin 18. Any unresolved chronic toxicity greater than CTCAE grade 2 from previous anticancer therapy 19. Participation in a clinical study and/or receipt of an investigational drug during the last 30 days participation in the survival follow-up period of a study is not an exclusion 20. Previous exposure to ZD6474 21. Currently pregnant or breast feeding
    E.5 End points
    E.5.1Primary end point(s)
    To demonstrate an improvement in progression-free survival PFS with ZD6474 as compared to placebo in subjects with unresectable locally advanced or metastatic MTC
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Information not present in EudraCT
    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. 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.8.3 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.8.5The trial involves multiple Member States Yes
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    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
    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 days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    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.1.3Elderly (>=65 years) Yes
    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 Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2007-03-22. Yes
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    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 state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 106
    F.4.2.2In the whole clinical trial 232
    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 Decision2007-03-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-01-25
    P. End of Trial
    P.End of Trial StatusCompleted
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