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    Summary
    EudraCT Number:2014-005491-28
    Sponsor's Protocol Code Number:MO29594
    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:2021-06-04
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2014-005491-28
    A.3Full title of the trial
    A MULTICENTRE OPEN-LABEL, SINGLE ARM PHASE II STUDY EVALUATING THE SAFETY AND EFFICACY OF BEVACIZUMAB IN COMBINATION WITH CARBOPLATIN AND PACLITAXEL IN PATIENTS WITH METASTATIC, RECURRENT OR PERSISTENT CERVICAL CANCER
    STUDIO DI FASE II MULTICENTRICO, IN APERTO, A BRACCIO SINGOLO, PER VALUTARE SICUREZZA ED EFFICACIA DI BEVACIZUMAB IN ASSOCIAZIONE A CARBOPLATINO E PACLITAXEL IN PAZIENTI CON TUMORE DELLA CERVICE UTERINA METASTATICO, RICORRENTE O PERSISTENTE
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    STUDY EVALUATING BEVACIZUMAB IN COMBINATION WITH CARBOPLATIN AND PACLITAXEL IN WOMEN WITH METASTATIC, RECURRENT OR PERSISTENT CERVICAL CANCER
    STUDIO PER LA VALUTAZIONE DI BEVACIZUMAB IN COMBINAZIONE CON CARBOPLATINO E PACLITAXEL IN DONNE CON CARCINOMA DELLA CERVICE RICORRENTE O PERSISTENTE
    A.3.2Name or abbreviated title of the trial where available
    -
    -
    A.4.1Sponsor's protocol code numberMO29594
    A.5.4Other Identifiers
    Name:-Number:-
    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 SponsorF. HOFFMANN - LA ROCHE LTD.
    B.1.3.4CountrySwitzerland
    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 supportF. HOFFMANN - LA ROCHE LTD
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. HOFFMANN - LA ROCHE LTD
    B.5.2Functional name of contact pointTRIAL INFORMATION SUPPORT LINE-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGRENZACHERSTRASSE 124
    B.5.3.2Town/ cityBASEL
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number-
    B.5.5Fax number-
    B.5.6E-mailglobal.rochegenentechtrials@roche.com
    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 Avastin
    D.2.1.1.2Name of the Marketing Authorisation holderROCHE REGISTRATION LIMITED
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    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) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 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 Yes
    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 typeAnticorpo monoclonale ricombinante umanizzato
    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.2.1.1.1Trade name Carboplatin 10 mg
    D.2.1.1.2Name of the Marketing Authorisation holderHospira UK Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 41575-94-4
    D.3.9.2Current sponsor codeRO484-3791
    D.3.9.4EV Substance CodeSUB06614MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 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 Yes
    D.3.11.13.1Other medicinal product typeCarboplatino è un agente antineoplastico.
    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 CARBOPLATIN 10 MG/ML
    D.2.1.1.2Name of the Marketing Authorisation holderHOSPIRA UK LIMITED
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 41575-94-4
    D.3.9.2Current sponsor codeRO484-3791
    D.3.9.4EV Substance CodeSUB06614MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number450
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 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 Yes
    D.3.11.13.1Other medicinal product typeCarboplatino è un agente antineoplastico.
    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 Carboplatin 10 mg/ml
    D.2.1.1.2Name of the Marketing Authorisation holderSUN PHARMACEUTICAL INDUSTRIES
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 41575-94-4
    D.3.9.2Current sponsor codeRO484-3791
    D.3.9.4EV Substance CodeSUB06614MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 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 Yes
    D.3.11.13.1Other medicinal product typeCarboplatino è un agente antineoplastico
    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 CARBOPLATIN 10 MG/ML
    D.2.1.1.2Name of the Marketing Authorisation holderSUN PHARMACEUTICAL INDUSTRIES EUROPE B.V.
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 41575-94-4
    D.3.9.2Current sponsor codeRO484-3791
    D.3.9.4EV Substance CodeSUB06614MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number450
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 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 Yes
    D.3.11.13.1Other medicinal product typeCarboplatino è un agente antineoplastico.
    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 BENDATAX
    D.2.1.1.2Name of the Marketing Authorisation holderBENDALIS GmbH
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 33069-62-4
    D.3.9.2Current sponsor codeRO024-7506
    D.3.9.4EV Substance CodeSUB09583MIG
    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) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 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 Yes
    D.3.11.13.1Other medicinal product typeAlcaloidi vegetali e altri prodotti naturali
    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.2.1.1.1Trade name Paclitaxel Teva 6 mg/ml
    D.2.1.1.2Name of the Marketing Authorisation holderTEVA PHARMA S.L.U.
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 33069-62-4
    D.3.9.2Current sponsor codeRO024-7506
    D.3.9.4EV Substance CodeSUB09583MIG
    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) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 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 Yes
    D.3.11.13.1Other medicinal product typeAlcaloidi vegetali e altri prodotti naturali
    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 RECURRENT OR PERSISTENT CERVICAL CANCER
    TUMORE DELLA CERVICE UTERINA METASTATICO, RICORRENTE O PERSISTENTE
    E.1.1.1Medical condition in easily understood language
    CERVICAL CANCER IS A DISEASE IN WHICH THE CELLS OF THE CERVIX BECOME ABNORMAL AND START TO GROW UNCONTROLLABLY, FORMING TUMORS
    Il cancro della cervice uterina è una malattia in cui le cellule della cervice diventano anormali e iniziano a crescere in maniera incontrollata, formando tumori
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10008236
    E.1.2Term Cervical cancer stage IV
    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
    To determine the safety of bevacizumab in combination with carboplatin and paclitaxel therapy for metastatic, recurrent or persistent cervical cancer, as defined by the frequency and severity of gastrointestinal (GI) perforation/fistula, G1-vaginal fistula and genitourinary (GU) fistula events
    Determinare la sicurezza della terapia con bevacizumab in associazione a carboplatino e paclitaxel nel trattamento del tumore della cervice uterina metastatico, ricorrente o persistente, definito in base alla frequenza e alla gravità di eventi di perforazione/fistole gastrointestinali (GI), fistole GI-vaginali e fistole genitourinarie (GU).
    E.2.2Secondary objectives of the trial
    -To define the safety and tolerability of bevacizumab in combination with carboplatin and paclitaxel therapy for recurrent, persistent or metastatic cervical cancer by describing the nature, frequency, severity and duration of adverse events (AEs)
    -To evaluate teh incidence of G1 perforation/fistula, G1-vaginal fistula and GU fistula events over time
    -To evaluate the efficacy of bevacizumab in combination with carboplatin and paclitaxel therapy for metastatic, recurrent or persistent cervical cancer, as measured by:
    - Progression-free survival determined by the investigator
    - Overall survival
    - Overall response rate (Investigator-assessed).
    • Definire la sicurezza e la tollerabilità della terapia con bevacizumab in associazione a carboplatino e paclitaxel nel trattamento del tumore della cervice uterina metastatico, ricorrente o persistente, illustrando la natura, la frequenza, la gravità e la durata degli eventi avversi (AE).
    • Valutare l'incidenza di eventi di perforazione/fistole GI, fistole GI-vaginali e fistole GU nel corso del tempo.
    • Valutare l'efficacia della terapia con bevacizumab in associazione a carboplatino e paclitaxel nel trattamento del tumore della cervice uterina metastatico, ricorrente o persistente, definito in base ai seguenti parametri:
    – Sopravvivenza libera da progressione (PFS), stabilita dallo sperimentatore
    – Sopravvivenza globale (OS)
    –Tasso di risposta complessiva (ORR; stabilito dallo sperimentatore).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Female aged >=18 years
    - Eastern Cooperative Oncology Group performance status score 0 or 1
    - Life expectancy >=3 months
    - Able (in the investigator's judgement) to comply with the study protocol.
    - Female patients of childbearing potential must agree with the required contraceptive methods as defined per protocol
    - Distant metastatic, recurrent or persistent squamous cell carcinoma,adenosquamous carcinoma or adenocarcinoma of the cervix that is not amenable to curative treatment with surgery and/or radiation therapy
    - Either measurable or non-measurable disease. If disease is nonmeasurable or limited to the radiation field, a biopsy or fine-needle aspiration is required to confirm malignancy
    - Eligible for carboplatin and paclitaxel chemotherapy in accordance
    with local standards of care
    - Adequate haematological, renal and hepatic function as defined in the protocol
    - Normal blood coagulation parameters
    - Recovered (to grade <=1) from the effects of prior surgery, radiation therapy or chemoradiotherapy. At least 6 weeks must have elapsed between the last dose of palliative radiation and the first dose of bevacizumab.
    • Donne di età =18 anni
    • Performance status ECOG = 0 o 1
    • Aspettativa di vita =3 mesi
    • Capacità (secondo il parere dello sperimentatore) di rispettare il protocollo dello studio
    - Donne in età fertile devono acconsentire a praticare i metodi contraccettivi definiti dal protocollo
    - Carcinoma a cellule squamose con metastasi a distanza, ricorrente o persistente, carcinoma adenosquamoso o adenocarcinoma della cervice non riconducibile ad un trattamento curativo con chirurgia e/o radioterapia.
    - Malattia misurabile oppure non misurabile ma confermata da biopsia. Se la malattia è non misurabile o limitata al campo di radiazione, una biopsia oppure un prelievo di agoaspirato viene richiesto per confermare la malattia.
    - Paziente eleggibile alla chemioterapia con carboplatino e paclitaxel ai sensi degli standard di cura locali.
    - Adeguata funzione ematologica, renale ed epatica, come definita nel protocollo
    - Parametri della coagulazione nella norma
    - Recupero (fino al ripristino di un grado =1) dagli effetti della precedente chirurgia, radioterapia o chemioradioterapia. Devono essere trascorse almeno 6 settimane tra l'ultima dose di radioterapia palliativa (per es. per dolore o sanguinamento) e la prima dose di bevacizumab
    E.4Principal exclusion criteria
    - Pregnant or lactating women
    - History of other malignancy within 5 years before screening, except for non-melanoma skin carcinoma
    - Ongoing disease involving the bladder or rectum at
    screening/baseline
    - Evidence of abdominal free air
    - Bilateral hydronephrosis, unless it can be alleviated by ureteral stent(s) or percutaneous drainage
    - Untreated central nervous system (CNS) metastases. Patients with adequately treated brain metastases/spinal cord compression that is
    stable without anti-cancer steroid treatment for >4 weeks are eligible.
    - Prior chemotherapy for recurrent, persistent or metastatic cervical cancer (prior adjuvant or neoadjuvant chemotherapy is permitted if
    completed >6 months before first study dose)
    - Prior chemoradiation within the 3 months preceding first study dose
    - Prior radiotherapy delivered using cobalt
    - Serious active infection requiring IV antibiotics at screening/baseline
    - Known active human immunodeficiency virus infection that is not adequately controlled
    - Prior or current bevacizumab or other anti-angiogenic treatment
    - Requirement for treatment with any medicinal product that contraindicates the use of any of the study drugs, may interfere with the planned treatment, affects patient compliance or puts the patient at high risk for treatment-related complications
    - Treatment with another investigational agent within 28 days or 2 investigational agent half-lives (whichever is longer) before first study
    dose
    - Current or recent (within 10 days before the first dose of study drug) chronic daily treatment with aspirin (>325 milligrams [mg]/day),clopidogrel (>75 mg/day), or current or recent (within 10 days before
    first dose of bevacizumab) use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes.
    - Major surgical procedure, open biopsy or significant traumatic injury within 28 days before the first dose of bevacizumab or anticipation of
    the need for major surgery during the course of study treatment.
    - Minor surgical procedure within 2 days before the first dose of studY drug
    - Any prior history of fistula or GI perforation
    - Clinical signs or symptoms of GI obstruction requiring parenteral hydration and/or nutrition
    - Intra-abdominal abscess within 6 months before the first dose of bevacizumab
    - Active GI bleeding or ulcer
    - History of Crohn's disease or inflammatory bowel disease
    - Prior bowel resection <=6 weeks preceding first study dose
    - History of diverticulitis requiring medical intervention
    - National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (version 4.0) grade >=2 enteritis
    - History of myocardial infarction, unstable angina, subarachnoid haemorrhage, stroke or transient ischaemic attack within 6 months before first dose of study drug
    - Uncontrolled hypertension (current systolic blood pressure [BP] >150 millimetre of mercury (mmHg) and/or diastolic BP >100 mmHg or history of hypertensive crisis or hypertensive encephalopathy)
    - Clinically significant active cardiovascular disease
    - Serious cardiac arrhythmia requiring medication. This does not include asymptomatic atrial fibrillation with controlled ventricular rate - NCI CTCAE (vers. 4.0) grade >=2 peripheral vascular disease
    - History or evidence upon physical/neurological examination of CNS disease unrelated to cancer unless adequately treated with standard
    medical therapy - Significant vascular disease within 6 months before study enrolment - Pre-existing NCI CTCAE (version 4.0) grade >=2 peripheral neuropathy
    - History or evidence of inherited bleeding diathesis or coagulopathywith the risk of bleeding
    - Serious or non-healing open wound, peptic ulcer or incompletelyhealed non-radiation-related bone fracture
    - Known hypersensitivity to bevacizumab or any of its excipients,
    Chinese hamster ovary cell products or other recombinant human or humanised antibodies to any planned chemotherapy
    - History or evidence of NCI CTCAE (version 4.0) grade >=1 arterial thromboembolic event within the 6 months preceding first dose of study drug
    - History of any grade >=3 venous thromboembolic event
    - Evidence of any other disease, neurologic or metabolic dysfunction
    Donne in gravidanza o in allattamento -Storia di altre neoplasie maligne nei 5 anni prec.lo screening, eccetto carcinoma cutaneo diverso dal melanoma-Patologia in atto allo screening/basale che coinvolge vescica o retto -Evidenza di aria libera nell'addome -Idronefrosi bilaterale, se non alleviabile mediante uno o più stent ureterali o drenaggio percutaneo-Metastasi del sistema nervoso centrale (SNC) non trattate. Le paz.con metastasi cerebrali/compressione del midollo spinale adeguatamente trattate,che siano stabili senza trattamento antitumorale con steroidi da più di 4 settimane sono eleggibili -Precedente chemioterapia per cancro della cervice uterina ricorrente,persistente o metastatico(una precedente chemioterapia adiuvante o neoadiuvante è consentita se completata più di 6 mesi prima della 1°dose del trattamento in studio)- Chemioradioterapia nei 3 mesi prec. la 1°dose del trattamento in studio-Precedente radioterapia erogata utilizzando cobalto.-Presenza allo screening/basale di una grave infezione attiva che necessiti di antibiotici per via EV -Nota infezione da HIV attiva non adeguatamente controllata -Trattamento precedente o corrente con bevacizumab o altra terapia anti-angiogenica -Necessità di trattamento con qualsiasi medicinale che controindichi l'utilizzo di uno qualsiasi dei farmaci in studio, che potrebbe interferire con il trattamento pianificato, influire sulla compliance della paz. o porre la paz.ad alto rischio di sviluppare complicanze correlate al trattamento -Trattamento con un altro agente sperimentale nei 28 giorni o 2 emivite dell'agente sperimentale (dei 2 periodi il più lungo)prec. la 1°dose del trattamento in studio -Trattamento quotidiano cronico, corrente o recente(nei 10 giorni precedenti la 1°dose del trattamento in studio),con aspirina (>325 mg/die),clopidogrel(>75 mg/die)o utilizzo corrente o recente (nei 10 giorni prec. la 1°dose di bevacizumab)di anticoagulanti orali o parenterali o di agenti trombolitici a scopo terapeutico-Procedura di chirurgia maggiore, biopsia a cielo aperto o lesione traumatica significativa nei 28 giorni prec. la 1°dose di bevacizumab, oppure necessità prevista di ricorrere a chirurgia maggiore durante il trattamento in studio -Procedura di chirurgia minore nei 2 giorni precedenti la prima dose del farmaco in studio- Qualsiasi prec. fistola o perforazione GI- Segni clinici o sintomi di ostruzione GI che richieda idratazione e/o nutrizione parenterale- Ascesso intra-addominale nei 6 mesi prec. la 1°dose di bevacizumab - Emorragia o ulcera GI attive -Storia di malattia di Crohn o malattia infiammatoria intestinale-Resezione intestinale nelle =6 settimane prec, la 1°dose del trattamento in studio -Precedenti di diverticolite con necessità di intervento medico -Enterite di grado NCI CTCAE (versione 4.0) =2 -Storia di infarto del miocardio, angina instabile, emorragia subaracnoidea, ictus o attacco ischemico transitorio nei 6 mesi prec. la 1°dose del farmaco in studio -Ipertensione non adeguatamente controllata (attuale pressione arteriosa sistolica >150 mmHg e/o diastolica>100 mmHg oppure storia di crisi ipertensiva o encefalopatia ipertensiva)- Malattia cardiovascolare clinicamente significativa (es.classe New York Heart Association II o maggiore oppure insufficienza cardiaca congestizia [ICC] o aneurisma aortico)- Grave aritmia cardiaca con necessità di terapia farmacologica. È esclusa la fibrillazione atriale asintomatica con frequenza ventricolare controllata- Vasculopatia periferica di grado NCICTCAE(vers.4.0) =2-Storia o evidenza all’esame obiettivo/neurologico di malattia dell’SNC(es. convulsioni) non correlata al tumore,se non adeguatamente trattata con una terapia medica convenzionale -Significativa vasculopatia(es.aneurisma aortico con necessità di riparazione chirurgica o recente trombosi arteriosa) nei 6 mesi prec. l'arruolamento nello studio -Neuropatia periferica preesistente di grado NCI CTCAE (Vers.4.0) =2 -Storia o evidenza di diatesi emorragica o coagulopatia ereditarie con rischio di sanguinamento -Storia di ferita aperta o ulcera peptica grave o con difficoltà di cicatrizzazione,o di frattura ossea non correlata a radiazioni non completamente risolta - Nota ipersensibilità a bevacizumab o a uno qualsiasi dei suoi eccipienti, ai prodotti a base di cellule di ovaio di hamster cinese o ad altri anticorpi umani ricombinanti o anticorpi umanizzati o a uno qualsiasi degli agenti chemioterapici previsti -Storia o evidenza di eventi tromboembolici arteriosi (ETA) di grado NCI CTCAE (vers.4.0) =1 nei 6 mesi prec. la 1°dose del farmaco in studio -Storia di qualsiasi evento tromboembolico venoso (TEV) di grado =3 -Evidenza di qualsiasi altra malattia, disfunzione neurologica o metabolica
    E.5 End points
    E.5.1Primary end point(s)
    Incidence of GI perforation/fistula, GI-vaginal fistula and GU fistula (separately; all grades, grade 3/4 and grade 5)
    Incidenza di perforazione/fistole GI, fistole GI-vaginali e fistole GU (separatamente; di tutti i gradi, di grado 3/4 e di grado 5)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to 42 months
    Fino a 42 mesi
    E.5.2Secondary end point(s)
    1) Time to first GI perforation/fistula, GI-vaginal fistula and GU fistula
    2) Overall survival
    3) Overall response rate
    4) Progression-free survival (after first study dose bevacizumab or
    chemotherapy)
    5) Treatment exposure (dose and duration of treatment for each drug)
    6) Incidence of AEs, Serious AEs, and AEs of special interest for
    bevacizumab
    7) Changes in physical findings and clinical laboratory results during and
    following bevacizumab administration
    8) AEs leading to treatment interruption or permanent discontinuation of
    any study drug
    9) Cause of death
    1)Tempo alla prima perforazione/fistola GI, fistola GI-vaginale e fistola GU
    2) Sopravvivenza globale (OS) 3)Tasso di risposta complessiva
    4) Sopravvivenza libera da progressione (PFS) dopo la prima dose di bevacizumab o chemioterapia
    5) Esposizione al trattamento (dose e durata del trattamento per ciascun farmaco)
    6) incidenza di AE, SAE e AE di interesse speciale (AESI) relativi al bevacizumab
    7) Variazioni dei risultati dell'esame obiettivo e delle analisi di laboratorio durante e dopo la somministrazione di bevacizumab
    8) AE che determinano l'interruzione del trattamento o la sospensione permanente di qualsiasi farmaco in studio
    9) Causa del decesso.
    E.5.2.1Timepoint(s) of evaluation of this end point
    For all above listed (1-9.) secondary end points: Up to 42 months
    Per tutti gli end-point secondari elencati (da 1 a 9) : fino a 42 mesi
    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 No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    Tollerabilità
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    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 No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    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
    Argentina
    Bolivia, Plurinational State of
    Brazil
    Bulgaria
    Colombia
    Costa Rica
    Ecuador
    France
    Greece
    Guatemala
    Hungary
    Italy
    Mexico
    Panama
    Peru
    Poland
    Portugal
    Romania
    Russian Federation
    Serbia
    South Africa
    Spain
    Turkey
    Venezuela, Bolivarian Republic of
    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 this study is defined as the date when all patients have been followed up for survival for 24 months from enrolment (or have died, withdrawn from the study, been lost to follow-up, or the study has been terminated by the sponsor, if earlier).
    Si definisce conclusione dello studio la data in cui tutte le pazienti saranno state sottoposte a follow-up per la sopravvivenza per 24 mesi dall'arruolamento (o saranno decedute, si saranno ritirate dallo studio, saranno perse al follow-up o lo studio sarà stato interrotto dallo sponsor, se tali eventi si verificheranno prima)
    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 months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months6
    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 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.1.2.1Number of subjects for this age range: 125
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 25
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 90
    F.4.2.2In the whole clinical trial 150
    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)
    At the end of the trial patients still receiving treatment will continue to receive bevacizumab (provided by the Sponsor) by consenting to be rolled over into a separate protocol (AVALTE, MO25757). The AVALTE (MO25757) roll-over study is designed to allow treatment continuation of bevacizumab until PD, unacceptable toxicity, withdrawal of the patient, the physician's decision to stop treatment, or an absolute contraindication to repeated treatment.
    Al termine dello studio i pazienti ancora in trattamento continueranno a ricevere bevacizumab (fornita dallo Sponsor) acconsentendo ad essere arruolati in uno studio di roll over (AVALTE, MO25757), che ha lo scopo di permettere la prosecuzione del trattamento fino a progressione di malattia (PD), tossicità inaccettabile, ritiro del consenso da parte della paziente,decisione del medico di interrompere il trattamento, o una controindicazione assoluta a trattamenti ripetuti
    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 Decision2015-05-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-04-29
    P. End of Trial
    P.End of Trial StatusCompleted
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