Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43846   clinical trials with a EudraCT protocol, of which   7282   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.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2004-000379-32
    Sponsor's Protocol Code Number:D4200C0007A
    National Competent Authority:Finland - Fimea
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2004-07-08
    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 ConcernedFinland - Fimea
    A.2EudraCT number2004-000379-32
    A.3Full title of the trial
    A Randomized, Partially Blinded, Phase II Study to Assess the Safety, Tolerability, and Efficacy of ZD6474 Alone or in Combination with Paclitaxel and Carboplatin in Subjects with Previously Untreated Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)
    A.3.2Name or abbreviated title of the trial where available
    6474IL0007
    A.4.1Sponsor's protocol code numberD4200C0007A
    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 Information not present in EudraCT
    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 nameZD6474 Tablets
    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.3.9.1CAS 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 number200, 300
    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
    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
    Time to progression (TTP). A comparision will be made of ZD6474 alone (300 mg PO daily), ZD6474 in combination with paclitaxel/carboplatin, and paclitaxel/carboplatin alone
    E.2.2Secondary objectives of the trial
    The secondary objectives of the randomized phase are the following:

    Tumor response rates, safety and tolerability, Quality of Life, survival, pharmacokinetics


    Comparisions will be made of ZD6474 alone (300 mg PO daily), ZD6474 in combination with paclitaxel/carboplatin, and paclitaxel/carboplatin alone
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    For inclusion in the study, patients must fulfill all of the following criteria:

    1. Provision of written informed consent;

    2. Age 18 years or older;

    3. Histologically or cytologically confirmed locally advanced (Stage IIIb with pleural effusion) or metastatic (Stage IV) NSCLC with no evidence of mixed small cell and non-small cell histology. (Patients with previously resected early stage non-small cell lung cancer (Stages I-III) who have relapsed and have not been treated with chemotherapy or radiotherapy are also eligible);

    4. Considered suitable for first line treatment of NSCLC with paclitaxel/carboplatin and ZD6474 with no prior chemotherapy, biological therapy, or radiation therapy, not including adjuvant or neoadjuvant therapy, radiation to the brain, or radiation to a bone metastasis for palliation;

    5. One or more measurable lesions at least 10 mm in the longest diameter by spiral CT scan or 20 mm with conventional techniques (according to RECIST);

    6. WHO performance status 0 or 1;

    7. Life expectancy of more than 12 weeks.

    PET inclusion (for selected centers)

    1. One or more measurable lesions greater than 20mm diameter (by spiral CT or conventional CT) in all dimensions to be followed as target lesions on RECIST;

    2. The whole lesion and the left ventricle or aorta must be in the same field of view for the PET;

    3. Fasting blood glucose < 150 mg/dL at baseline;

    4. In the clinical judgment of the investigator, the patient will be able to comply with the requirements of PET imaging (i.e., lie on the couch with arms up for the duration of the study).
    E.4Principal exclusion criteria
    Any of the following is regarded as a criterion for exclusion from the study:

    1. Brain metastases or spinal cord compression, unless treated at least 4 weeks before entry, and stable without steroid treatment for 1 week;

    2. Currently active skin disease, i.e., acne, psoriasis, eczema;

    3. Currently active gastrointestinal disease that may affect the ability of the patient to absorb the ZD6474 or tolerate diarrhea;

    4. History of clinically significant hemoptysis in the past 3 months;

    5. Neutrophils less than 1.5 x 109/L (1,500/mm3) or platelets less than 100, 000/mm3;

    6. Serum bilirubin >1.5 x the upper limit of reference range (ULRR);

    7. Creatinine clearance < 30 ml/min, calculated from serum creatinine;
    8. ALT or AST greater than 2.5 x ULRR if no demonstrable liver metastases; ALT or AST greater than 5.0 x ULRR if judged by the investigator to be related to liver metastases;

    9. Alkaline phosphatase greater than 2.5 x ULRR;

    10. Potassium concentration less then 3.5mEq/L, calcium (ionized calcium or adjusted for albumin) or magnesium concentrations outside normal limits. Supplementation of electrolytes is permitted;

    11. History of chronic atrial fibrillation or clinically significant arrhythmia (multifocal PVCs, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE grade 3) or a symptomatic sustained ventricular tachycardia;

    12. Significant cardiac event (including symptomatic heart failure or symptomatic angina) within 3 months of entry; or any cardiac disease that in the opinion of the investigator increases risk of ventricular arrhythmia;

    13. Previous history of QT prolongation while taking other medication unless agreed between the investigator and AstraZeneca;

    14. Congenital long QT syndrome;

    15. QT with Bazett’s correction unmeasurable or 460 msec or greater on screening ECG (Note for the randomized phase only: If a patient has QTc of 460 msec or greater on screening ECG, the screening ECG may be repeated, at least 24 hours after the first ECG. The average QTc from the two screening ECGs must be less than 460 msec in order for the patient to be eligible for the study. If the patient meets eligibility requirements, the “baseline” QTc for this patient will be the average of the three ECGs (screen 1, screen 2, and pre-1st dose));

    16. Superior Vena Cava (SVC) syndrome;

    17. Left ventricular ejection fraction (LVEF) less than 45% measured by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) for patients with previous anthracycline therapy (total dose > 450 mg/m2) or significant cardiovascular disease or chest irradiation;

    18. Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mg Hg);

    19. 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;

    20. Any pre-study or concomitant therapy as outlined in Section 3.5.4 of the protocol unless agreed between the investigator and AstraZeneca;

    21. Participation in an investigational trial within the past 30 days;

    22. Women of childbearing potential with a positive pregnancy test prior to receiving trial medication or breast-feeding women;

    23. Men or women unwilling to use an acceptable method of contraception while on study;

    24. Patients with co-existing malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ.

    PET exclusion (for selected centers)

    1. Bronchoalveolar carcinoma;

    2. All suitable measurable lesions are Pancoast;

    3. All suitable measurable lesions are too close to heart or aorta and would, in the opinion of the investigator, result in spill over on PET imaging contaminating lesion uptake measurements;

    4. Type I insulin dependent diabetics;

    5. Poorly controlled Type II insulin independent diabetes where the blood glucose is greater than 150 mg/dL;

    6. Patients taking concomitant medication at the time of PET scanning which may effect glucose metabolism, i.e., Decadron;

    7. Clinical judgment by the investigator that the patient should not participate in PET imaging.
    E.5 End points
    E.5.1Primary end point(s)
    The study will be conducted in two parts. The run-in phase (which is being conducted in the USA) will determine the dose of ZD6474 to be used in combination with paclitaxel + carboplatin chemotherapy. The randomised phase (to be conducted in the EU and elsewhere) will then use a 3 arm design with a 2:1:1 randomisation scheme to the following study arms
    Arm 1; ZD6474 300mg alone
    Arm 2; ZD6474 (dose to be determined from run-in phase) plus chemotherapy
    Arm 3; Matched placebo to ZD6474 plus chemotherapy

    For arms 2 and 3, chemotherapy is defined as Paclitaxel (200 mg/m2) administered IV over 3 hours in Cycle 1 and over 60-90 minutes in all subsequent cycles, once every 3 weeks plus carboplatin (AUCSS 6) administered IV over 30-60 minutes in all cycles, once every 3 weeks. A maximum of 6 cycles of chemotherapy will be administered, after which time (if subjects have not progressed), subjects will continue on either ZD6474 or matched placebo alone.

    The study is partially blinded - investigators and subjects in arm 1 will be aware that this arm is ZD6474 monotherapy, but arms 2 and 3 will be double blind

    The primary endpoint is efficacy (for all treatment arms), defined as time to tumour progression, which will be assessed regularly, using RECIST criteria
    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 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 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 No
    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 Yes
    E.8.1.7.1Other trial design description
    Partially blinded
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.3.1Comparator description
    Paclitaxel/carboplatin - to be sourced locally and used in accordance with local SmPCs
    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
    All patients in the run-in and randomized phases will be followed for survival for a minimum
    of 2 years after the last patient enters the study.
    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 days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    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 2004-07-08. 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.3.3.6.1Details of subjects incapable of giving consent
    Women of child-bearing potential (and their partners) will be required to use adequate contraceptive measures
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 80
    F.4.2.2In the whole clinical trial 200
    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)
    Normal treatment will apply after subjects end their participation in the study
    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 Decision2004-09-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2004-08-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2007-03-23
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri Apr 19 14:33:06 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA