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    Summary
    EudraCT Number:2006-002384-12
    Sponsor's Protocol Code Number:D4200C00044
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2006-09-27
    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 ConcernedGermany - BfArM
    A.2EudraCT number2006-002384-12
    A.3Full title of the trial
    A Phase III, International, Randomised, Double-Blind, Parallel-Group, Multi-Centre Study to Assess the Efficacy of ZD6474(ZACTIMA™) Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Patients With Locally Advanced or Metastatic (Stage IIIB – IV) Non-Small Cell Lung Cancer (NSCLC) after Prior Therapy with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI)
    A.4.1Sponsor's protocol code numberD4200C00044
    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 AB
    B.1.3.4CountrySweden
    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.4.2Country
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameZACTIMA
    D.3.2Product code ZD6474
    D.3.4Pharmaceutical form 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 INNvandetanib
    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 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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee 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.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 No
    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 nameZACTIMA
    D.3.2Product code ZD6474
    D.3.4Pharmaceutical form 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 INNvandetanib
    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.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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee 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 placeboTablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    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
    Non-small cell lung cancer
    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 demonstrate an improvement in overall survival for ZD6474 (ZACTIMA™ ) plus best supportive care (BSC) compared with placebo plus BSC in patients with locally advanced or metastatic NSCLC after prior therapy with an EGFR TKI
    E.2.2Secondary objectives of the trial
    To demonstrate an improvement in progression-free survival (PFS) for ZD6474(ZACTIMA) plus BSC compared with placebo plus BSC

    To demonstrate an improvement in the overall objective response rate (ORR) (complete response [CR] + partial response [PR]), disease control rate (DCR) (CR + PR + Stable Disease [SD] ≥ 8 weeks) and duration of response (DOR) for ZD6474 plus BSC compared with placebo plus BSC using Response Evaluation Criteria in Solid Tumours (RECIST)

    To study the safety and tolerability of ZD6474 plus BSC compared with placebo plus BSC

    To demonstrate beneficial effects in time to deterioration of disease-relatedsymptoms (TDS) assessed by the combined score of LCS, pain and fatigue for ZD6474 plus BSC compared with placebo plus BSC
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Provision of informed consent
    2. Female or male aged 18 years and over
    3. Histologic or cytologic confirmation of locally advanced or metastatic NSCLC (IIIB-IV) on entry into study. (Sputum cytology alone is not acceptable. Cytology specimens obtained by brushing, washing or needle aspiration are acceptable.)
    4. Failure of prior therapy (during or after treatment) with an EGFR TKI (either radiological documentation of disease progression or due to toxicity) in patients who have received at least one but no more than two prior chemotherapy regimens.
    5. WHO Performance status 0 – 2
    6. Measurable disease defined as - one or more measurable lesions at least 10 mm in the longest diameter (LD) by spiral CT scan or 20 mm with conventional techniques according to RECIST
    7. Negative pregnancy test for women of childbearing potential
    8. Life expectancy of 12 weeks or longer
    E.4Principal exclusion criteria
    1. Mixed small cell and non–small-cell lung cancer histology
    2. Prior treatment with VEGFR TKIs (prior treatment with bevacizumab [Avastin] is permitted)
    3. Chemotherapy or other systemic anti-cancer therapy within 4 weeks (3 weeks for EGFR TKIs) before the start of study therapy (6 weeks for nitrosoureas,
    mitomycin and suramin).
    4. Three or more prior chemotherapy regimens for advanced disease (one additional regimen allowed for neoadjuvant or adjuvant therapy). Note; chemotherapy or other anti-cancer agents are not allowed during treatment with ZD6474 / Placebo.
    5. The last radiation therapy within 4 weeks before the start of study therapy, not including local palliative radiation.
    6. Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy
    7. Any unresolved toxicity > CTCAE grade 2 from previous anti-cancer therapy
    8. Serum bilirubin >1.5 x ULRR
    9. Creatinine Clearance < 30ml/min (calculated by Cockcroft-Gault formula [see appendix G])
    10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 x ULRR in the absence of liver metastases, or >5 x ULRR in the presence of liver metastases
    11. Alkaline phosphatase (ALP) >2.5 x ULRR in the absence of liver metastases, or >5 x ULRR in the presence of liver metastases
    12. Significant cardiovascular event (e.g. myocardial infarction, superior vena cava [SVC] syndrome), New York Heart Association [NYHA] classification of heart
    disease ≥2 [See Appendix H]) within 3 months before starting study therapy, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia
    13. 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 excluded.
    14. Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age
    15. QT prolongation with other medication that required discontinuation of that medication
    16. Presence of left bundle branch block (LBBB)
    17. QTc with Bazett’s correction unmeasurable or ≥480 msec or greater on screening ECG (Note: If a patient has a QTc interval ≥480 msec on screening ECG, the screening ECG may be repeated twice [at least 24 hrs apart]. The average QTc
    from the three screening ECGs must be <480 msec in order for the patient to be
    eligible for the study.). Patients who are receiving a drug that has a risk of QTc
    prolongation (see Appendix D, Table 2) are excluded if QTc is ≥ 460 msec.
    18. Potassium <4.0 mmol/L despite supplementation; serum calcium (or ionized or adjusted for albumin), or magnesium out of normal range despite supplementation
    19. Women who are pregnant or breast feeding
    20. Any concomitant medications that may cause QTc prolongation or induce Torsades de Pointes (see Appendix D for the lists of medications in Table 1 & Table 2) or induce CYP3A4 function (see Section 3.6.2) within 2 weeks of start of study
    therapy. Drugs listed in Appendix D, Table 2, that in the investigator’s opinion cannot be discontinued, are allowed, provided the precautions outlined in section 3.2.2.1 are adhered to.
    21. Known or suspected brain metastases or spinal cord compression, unless treated at least 4 weeks before starting study therapy, and stable without steroid
    treatment for 10 days
    22. Hypertension not controlled by medical therapy (systolic blood pressure > 160 millimetre of mercury [mmHg] or diastolic blood pressure >100 mmHg)
    23. Previous or current malignancies of other histologies within the last 5 years, with the exception of in situ carcinoma of the cervix and adequately treated basal cell or squamous cell carcinoma of the skin
    24. Evidence of severe or uncontrolled systemic disease or any concurrent condition (e.g. drug or alcohol abuse), which in the Investigator’s opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol
    25. Previous randomisation in the present study
    26. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff, PAREXEL and APEX staff or staff at the investigational site)
    27. Participation in a clinical study of any investigational agents within 30 days prior to starting study treatment
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome variable of this study is overall survival (OS) which is defined as the number of days from randomisation to death from any cause.
    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 No
    E.6.7Pharmacodynamic No
    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 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) Yes
    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.8.4.1Number of sites anticipated in Member State concerned19
    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 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 study will be declared once a program has been established that allows all remaining patients still receiving ZD6474 study treatment to receive open-label supplies after the final analysis of the study has occurred. The end of study will be when all patients have finished study therapy and all sites are closed.
    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 months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months4
    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 2006-09-27. Yes
    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 state166
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 350
    F.4.2.2In the whole clinical trial 930
    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 Decision2006-10-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2006-10-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-11-30
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