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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   38002   clinical trials with a EudraCT protocol, of which   6235   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).
     
    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:2006-004030-32
    Sponsor's Protocol Code Number:AIOKRK0306
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2009-09-17
    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 ConcernedAustria - BASG
    A.2EudraCT number2006-004030-32
    A.3Full title of the trial
    Randomised study for efficiency of FOLFIRI in combination with Cetuximab vs. Bevacizumab in first-line-therapy of metastatic colorectal cancer
    Randomisierte Studie zur Wirksamkeit von FOLFIRI in Kombination mit Cetuximab vs. Bevacizumab in der Erstlinien-Behandlung des metastasierten kolorektalen Karzinoms
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study with two treatment arms to assess the efficacy of FOLFIRI (chemotherapy regimen with folinic acid, fluorouracil and irinotecan) in combinations with one specific antibody (cetuximab vs. bevacizumab) in the first-line treatment of metastatic colorectal cancer.
    Eine Studie mit 2 Behandlungszweigen, um die Wirksamkeit von FOLFIRI (Chemotherapieschema mit den Wirkstoffen Folinsäure, Fluoruracil und Irinotecan) in Kombinationen mit jeweils einem bestimmten Antikörper (Cetuximab vs. Bevacizumab) in der Erstlinien-Behandlung des metastasierendem Darmkrebs.
    A.3.2Name or abbreviated title of the trial where available
    FIRE-3
    FIRE-3
    A.4.1Sponsor's protocol code numberAIOKRK0306
    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 SponsorKlinikum der Ludwig-Maximilians Universität München, Klinikum Großhadern
    B.1.3.4CountryGermany
    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 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 Yes
    D.2.1.1.1Trade name Campto
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameCampto
    D.3.2Product code Campto
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIRINOTECAN HYDROCHLORIDE
    D.3.9.1CAS number 100286906
    D.3.9.2Current sponsor codeCAMPTO
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 No
    D.3.11.8Extractive medicinal product No
    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 Information not present in EudraCT
    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 Yes
    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 nameFlourouracil
    D.3.2Product code 5-FU
    D.3.4Pharmaceutical form Concentrate for solution for injection
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFLUOROURACIL
    D.3.9.1CAS number 51218
    D.3.9.2Current sponsor code5-FU
    D.3.9.3Other descriptive name5-FU
    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 No
    D.3.11.8Extractive medicinal product No
    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: 3
    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 Erbitux 5 mg/ml
    D.2.1.1.2Name of the Marketing Authorisation holderMerck KGaA
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameErbitux
    D.3.2Product code Erbitux
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCETUXIMAB
    D.3.9.1CAS number 205923564
    D.3.9.2Current sponsor codeErbitux
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 No
    D.3.11.8Extractive medicinal product No
    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 Yes
    D.3.11.13.1Other medicinal product typemonoclonal antibody
    D.IMP: 4
    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 Avastin
    D.2.1.1.2Name of the Marketing Authorisation holderRoche
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameAvastin
    D.3.2Product code Avastin
    D.3.4Pharmaceutical form
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeAvastin
    D.3.9.3Other descriptive nameBEVACIZUMABUM
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 No
    D.3.11.8Extractive medicinal product No
    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: 5
    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 Campto
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameCampto
    D.3.2Product code Campto
    D.3.4Pharmaceutical form
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIRINOTECAN HYDROCHLORIDE
    D.3.9.1CAS number 100286906
    D.3.9.2Current sponsor codeCampto
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 No
    D.3.11.8Extractive medicinal product No
    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 Information not present in EudraCT
    D.IMP: 6
    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 Avastin
    D.2.1.1.2Name of the Marketing Authorisation holderRoche
    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 nameAvastin
    D.3.2Product code Avastin
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeAvastin
    D.3.9.3Other descriptive nameBEVACIZUMABUM
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 No
    D.3.11.8Extractive medicinal product No
    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: 7
    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.2.5The 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 nameFolinsäure
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFOLIC ACID
    D.3.9.1CAS number 59303
    D.3.9.3Other descriptive nameFolinsäure
    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 No
    D.3.11.8Extractive medicinal product No
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Metastatic colorectal cancer
    Metastasierender Darmkrebs
    E.1.1.1Medical condition in easily understood language
    Mcolorectal cancer
    Metastasierender Darmkrebs
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10052362
    E.1.2Term Metastatic colorectal cancer
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Comparative validation of antitumor efficacy measured by objective remissionrate defined by RECIST-criteria (OR= CR+ PR), assessed within intent-to-treat-collective.
    Vergleichende Bestimmung der Antitumorwirksamkeit (gemessen anhand der objektiven Remissionsrate) der additiven Gabe eines monoklonalen Antikörpers (Cetuximab vs. Bevacizumab) in Kombination mit der Basischemotherapie FOLFIRI.
    E.2.2Secondary objectives of the trial
    Determination of progression free survival
    Determination of overall survival
    Rate of liver resection with potentially curative approach
    Evaluation of safety and compatibility (NCI-CTCAE-criteria)
    Determination of time to failure of strategy
    Determination of remission depth (maximum relative remission of tumor burden compared to baseline)
    •Erfassung der progressionsfreien Überlebenszeit
    •Erfassung der Gesamtüberlebenszeit
    •Erfassung der Zeit bis zum Versagen der Erstlinientherapie (Time to failure of strategy = TFS)
    •Remissionstiefe (maximale prozentuale Veränderung der Tumorgröße zu Baseline)
    •Rate an sekundären Resektionen von Lebermetastasen mit potentiell kurativem Ansatz
    •Erfassung der Sicherheit und Verträglichkeit (NCI-CTCAE V3.0 Kriterien)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -Histologically confirmed adenocarcinoma of colon and rectum
    -confirmation of a K-RAS wild type status (in the primary tumor or in metastasis)
    -stage IV
    -general condition: 0-2 (ECOG/ WHO)
    -suitable for application of chemotherapy
    -written informed consent (first and second-line therapy)
    -Age 18- 75
    -clinical or ambulant treatment
    -Life expectancy > 3 months
    -minimum one measurable indicator leasion according to RECIST. Evaluation of tumor manifestation 2 weeks or less before study entry.
    -Male or female patients with reproductive potential must use an approved contraceptive method
    -Leucocytes ≥ 3,0 x 10\9/L with Neutrophils ≥ 1,5 x 10\9/L, Thrombocytes ≥ 100 10\9/L, Hemoglobin ≥ 5,6 mmol/L equivalent to 9 g/dL
    -Serum bilirubin ≤ 1,5x upper NL
    -ALAT and ASAT ≤ 2,5 x upper NL, in case of liver metastases ALAT and ASAT ≤ 5 x upper NL.
    -Serum creatinine ≤ 1,5 x upper NL
    -An operation has to take place 4 weeks before study entry; a fine needle biopsy must have been performed more than 1 week ago. Wounds must have completely healed. The necessity of a big operation in the course of the study is not to be expected. An exception is a resection of liver metastases. If there should be the option of a secondary curative operation Bevacizumab has to be discontinued 6 to 8 weeks before operation.
    -relevant toxicitys of therapies prior must have abated
    - Histologisch gesichertes Adenokarzinom des Kolons oder Rektums Stadium IV
    - Nachweis des K-RAS- Wildtyp-Status im Tumor (Primärtumor oder Metastase)
    - Allgemeinzustand: 0 - 2 (ECOG/WHO)
    - Für die Applikation einer Chemotherapie geeignet
    - Schriftliche Einverständniserklärung des Patienten (Erst- und Zweitlinientherapie)
    - Alter 18 - 75 Jahre
    - Stationäre oder ambulante Behandlung
    - Geschätzte Lebenserwartung > 3 Monate
    - Vorliegen mindestens einer messbaren Indikatorläsion entsprechend der RECIST-Kriterien. Evaluation der Tumormanifestation 2 Wochen oder weniger vor Aufnahme in die Studie.
    - Effektive kontrazeptive Maßnahmen bei Männern und Frauen, soweitdie Möglichkeit einer Konzeption besteht
    - Leukozyten ≥ 3,0 x 109/L mit Neutrophilen ≥ 1,5 x 109/L, Thrombozyten ≥ 100 x 109/L, Hämoglobin ≥ 5,6 mmol/L (entspr. 9 g/dL)
    - Serumbilirubin ≤ 1,5x obere Normwertgrenze
    - ALAT und ASAT ≤ 2,5 x obere Normwertgrenze, bei Vorliegen von Lebermetastasen ALAT und ASAT ≤ 5 x obere Normwertgrenze.
    - Serumkreatinin ≤ 1,5 x obere Normwertgrenze
    - Eine Operation muss länger als 4 Wochen, eine Feinnadelbiopsie länger als 1 Woche vor Aufnahme in die Studie zurückliegen. Die Operationswunden müssen komplett verheilt sein. Die Notwendigkeit einer großen Operation im Verlauf der Studie ist nicht zu erwarten, ausgenommen ist eine evtl. Resektion von Lebermetastasen. Sollte die Option für eine sekundär kurative OP bestehen, so sollte Bevacizumab 6 bis 8 Wochen bzw. Cetuximab ca. 2 Wochen vor OP abgesetzt werden.
    - Relevante Toxizitäten vorheriger Therapien müssen abgeklungen sein
    E.4Principal exclusion criteria
    - confirmation of a K-RAS mutation
    - previous exposure to EGFR-targeting therapy
    - previous treatment with Bevacizumab
    - prior chemotherapy of colorectal cancer, except adjuvant chemotherapy which was terminated at least 6 month before study entry
    - experimental medical treatment within 30 days before study entry
    - known hypersensitivity to elements of the study drug
    - pregnant (exclusion diagnosis by beta-hCG-test) or breast-feeding women
    - clinically relevant coronary disease or myocardial infarction within 12 months before study entry or enhanced risk of uncontrolled arrhythmia
    - acute or subacute intestinal obstruction or chronical-inflammatory enteritis during anamnesis or chronical diarrhea
    - symptomatic peritoneal carcinosis
    - serious, non-healing wounds, ulcera or bone fracture
    - uncontrolled hypertonia
    - pronounced proteinuria
    - arterial thromboembolism or haemorrhage within 6 months before study entry (except tumor bleeding before tumorresection)
    - hemorrhagic diathesis or thrombotic tendency
    - therapeutic anticoagulation (marcumar-therapy, PTT-effective heparinization)
    - known DPD-insufficience (special screening not necessary)
    - known glucuronisation defect (Gilbert´s disease) (special screening not necessary)
    - secondary malignancies during anamnesis within the last 5 years except curatively treated basalioma or in situ carcinoma of the cervix
    - known alcohol- or drug abuse
    - clinical or psychological disorders that would prohibit to give a valid informed consent or to perform the study
    - a significant concomitant disorder which excludes the patient´s participation in from the study in the opinion of the responsible physician
    - absent or constricted legal capacity
    - Nachweis einer K-RAS-Mutation
    - Vorangegangene Behandlung mit einem gegen das EGFR-Target gerichteten Therapie
    - Vorangegangene Behandlung mit Bevacizumab
    - Vorangegangene Chemotherapie des kolorektalen Karzinoms mit Ausnahme einer adjuvanten Therapie, die mindestens 6 Monate vor Studieneintritt beendet wurde
    - Experimentelle medikamentöse Behandlung innerhalb von 30 Tagen vor Aufnahme
    - Bekannte Hypersensitivität gegen einen Bestandteil der Studienmedikation
    - Schwangerschaft (Ausschluss durch beta-hCG-Test sicherzustellen) oder Stillen
    - Bekannte oder klinisch vermutete Hirnmetastasen
    - Klinisch relevante koronare Herzerkrankung, Herzinfarkt während der letzten 12 Monate oder hohes Risiko unkontrollierter Arrhythmien
    - Akuter oder subakuter Darmverschluss oder chronisch-entzündliche Darmerkrankung in der Anamnese oder chronische Diarrhoe
    - Symptomatische Peritonealkarzinose
    - Schwere, nicht heilende Wunden, Ulcera oder Knochenfrakturen
    - Unkontrollierte Hypertonie
    - Ausgeprägte Proteinurie (nephrotisches Syndrom)
    - Arterielle Thromboembolien oder schwere Blutungen innerhalb von 6 Monaten vor Aufnahme in die Studie (Ausnahme Tumorblutung vor der Tumorresektionsoperation)
    - Hämorrhagische Diathese oder Thromboseneigung.
    - Therapeutische Antikoagulation (Marcumar-Therapie, PTT-wirksame Heparinisierung)
    - Bekannter DPD-Mangel (spezielles Screening nicht erforderlich)
    - Bekannter Glukuronidisierungsdefekt (Gilbert-Meulengracht-Syndrom) (spezielles Screening nicht erforderlich)
    - Zweitmalignom in der Anamnese während der letzten 5 Jahre, mit Ausnahme eines Basalioms oder eines in-situ-Karzinoms der Cervix uteri, soweit diese kurativ behandelt wurden.
    - Bekannter Alkohol- oder Drogenabusus
    - Medizinische oder psychologische Beeinträchtigungen, die eine ordnungsgemäße Einverständniserklärung oder Durchführung der Studie nicht erlauben
    - Eine signifikante Begleiterkrankung, die nach Ansicht des Prüfarztes die Teilnahme des Patienten an der Studie ausschließt
    - Fehlende oder eingeschränkte juristische Geschäftsfähigkeit
    E.5 End points
    E.5.1Primary end point(s)
    Progression of metastatic colorectal cancer or patient's death
    Tumorprogression oder Tod des Patienten
    E.5.1.1Timepoint(s) of evaluation of this end point
    Start of the end point evaluation is additive treatment with an antibody until tumor progression or death
    Beginn der Endpunktevaluierung ist die additive Antikörpergabe bis zur Tumorprogression oder Tod des Patienten
    E.5.2Secondary end point(s)
    •progression free survival
    •overall survival
    •time to failure of strategy = TFS
    •remission depth (maximum relative remission of tumor burden compared to baseline)
    •rate of liver metastases resection with potentially curative approach
    •Evaluation of safety and compatibility (NCI-CTCAE-V3.0 criteria)
    •progressionsfreie Überlebenszeit
    •Gesamtüberlebenszeit
    •Zeit bis zum Versagen der Erstlinientherapie (Time to failure of strategy = TFS)
    •Remissionstiefe (maximale prozentuale Veränderung der Tumorgröße zu Baseline)
    •Rate an sekundären Resektionen von Lebermetastasen mit potentiell kurativem Ansatz
    •Erfassung der Sicherheit und Verträglichkeit (NCI-CTCAE- V3.0 Kriterien)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Start of the end point evaluation is first the begin of tumor disease and second the additive antibody administration until tumor progression or patient death
    Beginn der Endpunktevaluierung ist einmal der Beginn der Tumorerkrankung und einmal die additive Antikörpergabe bis zur Tumorprogression oder Tod des Patienten
    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 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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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) 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 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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA150
    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 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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years11
    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 years11
    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.1.1.1In 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: 30
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 70
    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 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 2009-09-17. 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 state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 568
    F.4.2.2In the whole clinical trial 568
    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)
    Follow-up tumor assessments will be performed every 3 months after the end of therapy, until the patient is death or for a maximum of 5 years.
    Further treatment or observation of the patients is part of the routine medical care.
    According to patient information, subsequent medical treatment is discussed at the end of therapy within the study protocol between the physician and the patient taking into account known and accepted therapy options. The physician will suggest an adequate therapy.
    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 Decision2009-10-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-09-08
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2017-11-21
    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
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA