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   37700   clinical trials with a EudraCT protocol, of which   6177   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:2011-003308-18
    Sponsor's Protocol Code Number:MO27782
    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:2012-02-21
    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 number2011-003308-18
    A.3Full title of the trial
    A two-cohort, open-label, multicenter Phase II trial assessing the
    efficacy and safety of pertuzumab given in combination with
    trastuzumab and vinorelbine in first line patients with HER2-positive
    advanced (metastatic or locally advanced) breast cancer.
    Studio di fase II, a due coorti, multicentrico, in aperto, volto a valutare l'efficacia e la sicurezza di pertuzumab somministrato in associazione a trastuzumab e vinorelbina nel trattamento di prima linea di pazienti affetti da tumore mammario avanzato (metastatico o localmente avanzato) HER-2-positivo.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Randomized Phase II study of pertuzumab, trastuzumab and vinorelbine
    in patients with HER2-positive breast cancer.
    Studio randomizzato di fase II su pertuzumab, trastuzumab e vinorelbina in pazienti affetti da tumore mammario avanzato HER-2-positivo.
    A.3.2Name or abbreviated title of the trial where available
    VELVET
    VELVET
    A.4.1Sponsor's protocol code numberMO27782
    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 SponsorROCHE
    B.1.3.4CountryItaly
    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 organisationROCHE SPA
    B.5.2Functional name of contact pointHEAD OF CLINICAL OPERATIONS
    B.5.3 Address:
    B.5.3.1Street AddressVIALE GB STUCCHI 110
    B.5.3.2Town/ cityMONZA
    B.5.3.3Post code20900
    B.5.3.4CountryItaly
    B.5.4Telephone number039-2475070
    B.5.5Fax number039-2475085
    B.5.6E-mailsergio.scaccabarozzi@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 No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePertuzumab (rhuMAb 2C4)
    D.3.2Product code RO 4368451/F01
    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.3.8INN - Proposed INNPERTUZUMAB
    D.3.9.1CAS number 380610-27-5
    D.3.9.2Current sponsor codeRO4368451
    D.3.9.3Other descriptive nameNA
    D.3.9.4EV Substance CodeSUB16455MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number420
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 HERCEPTIN
    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 Powder 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.3.8INN - Proposed INNTRASTUZUMAB
    D.3.9.1CAS number 180288-69-1
    D.3.9.2Current sponsor codeRO 45-2317
    D.3.9.3Other descriptive nameNA
    D.3.9.4EV Substance CodeSUB12612MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    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 Bendarelbin
    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.3.8INN - Proposed INNVINORELBINE
    D.3.9.1CAS number 71486-22-1
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameNA
    D.3.9.4EV Substance CodeSUB00069MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleComparator
    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 Bendarelbin
    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.3.8INN - Proposed INNVINORELBINE
    D.3.9.1CAS number 71486-22-1
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameNA
    D.3.9.4EV Substance CodeSUB00069MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 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
    HER2-positive advanced (metastatic or locally advanced) breast cancer.
    Tumore mammario avanzato (metastatico o localmente avanzato) HER2 positivo.
    E.1.1.1Medical condition in easily understood language
    HER2-positive advanced breast cancer.
    Tumore mammario avanzato HER2 positivo.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10065430
    E.1.2Term HER-2 positive breast cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare objective overall response rates (ORR) assessed by a blinded independent review committee (IRC) of pertuzumab given in combination with trastuzumab and vinorelbine together in a single infusion bag versus conventional sequential administration in separate infusion bags.
    • Confrontare il tasso di risposte obiettive globali (ORR), valutate da un comitato di revisione indipendente (IRC) e operante in cieco, di pertuzumab somministrato in associazione a trastuzumab e vinorelbina, in una singola sacca per infusione rispetto alla convenzionale somministrazione sequenziale in sacche per infusione separate.
    E.2.2Secondary objectives of the trial
    o ORR assessed by the investigator o Time to response assessed by IRC and investigator o Duration of response assessed by IRC and investigator o Progression free survival (PFS) o Time to progression (TTP) o Overall survival (OS) o Safety and tolerability o Quality of life (EQ-5D and FACT-B questionnaires)
    o Tasso di ORR valutato dallo sperimentatore. o Tempo alla risposta valutato dall'IRC e dallo sperimentatore. o Durata della risposta valutata dall'IRC e dallo sperimentatore. o Sopravvivenza libera da progressione (PFS). o Tempo alla progressione (TTP). o Sopravvivenza globale (OS). o Sicurezza e tollerabilità. o Qualità di vita (questionari EQ-5D e FACT-B).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed written informed consent approved by the relevant Institutional Ethical Review Board (IRB). 2. Female or male patients aged 18 years or older. 3. Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection. 4. HER2-positive (defined as either immunohistochemistry [IHC] 3+ or in situ hybridization [ISH] positive) as assessed by local laboratory on primary or metastatic tumor (ISH positivity is defined as a ratio of 2.0 or greater for the number of HER2 gene copies to the number of signals for CEP17, or for single probe tests, a HER2 gene count greater than 4). 5. At least one measurable lesion and/or non-measurable disease evaluable according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (Eisenhauer et al. 2009). 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 7. Left ventricular ejection fraction (LVEF) of at least 55%. 8. Negative pregnancy test in women of childbearing potential (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization). 9. For women of childbearing potential who are sexually active, agreement to use a highly effective, nonhormonal form of contraception or two effective forms of non-hormonal contraception during and for at least 6 months post-study treatment. 10. Fertile males willing and able to use effective nonhormonal means of contraception (barrier method of contraception in conjunction with spermicidal jelly, or surgical sterilization) during and for at least 6 months post-study treatment. 11. Life expectancy of at least 12 weeks.
    I pazienti, per risultare idonei a partecipare a questo studio, devono soddisfare i seguenti criteri secondo le tempistiche previste dal Calendario delle valutazioni: 1. Firma del consenso informato scritto, approvato dal Comitato Etico (CE) di competenza. 2. Pazienti di ambo i sessi di età ≥ 18 anni. 3. Adenocarcinoma della mammella istologicamente o citologicamente confermato e documentato, con malattia metastatica o localmente avanzata non candidabile a resezione curativa. 4. Positività a HER-2 (definita come punteggio dell'esame immunoistochimico [IHC] 3+ o positività all'esame di ibridazione in situ [ISH]) del tumore primario o metastatico, secondo quanto stabilito da un laboratorio locale (la positività ISH è definita da un rapporto di 2,0 o maggiore del numero di copie di geni HER-2 rispetto al numero di segnali CEP17 oppure, per i test a sonda singola, da una conta dei geni HER-2 superiore a 4). 5. Almeno una lesione misurabile e/o malattia non misurabile valutabile in base ai Criteri di valutazione della risposta nelle neoplasie solide (RECIST), Versione 1.1 (Eisenhauer et al. 2009). 6. Punteggio del performance status secondo l'Eastern Cooperative Oncology Group (ECOG) di 0 o 1. 7. Frazione di eiezione del ventricolo sinistro (LVEF) almeno del 55%. 8. Test di gravidanza negativo nelle donne potenzialmente fertili (in premenopausa o in menopausa con amenorrea da meno di 12 mesi, non sottoposte a sterilizzazione chirurgica). 9. Per le donne potenzialmente fertili e sessualmente attive, accordo a utilizzare una forma di contraccezione non ormonale altamente efficace oppure due forme efficaci di contraccezione non ormonale durante lo studio e per almeno 6 mesi dopo la sospensione del trattamento in studio. 10. Gli uomini fertili devono essere disposti ed essere in grado di utilizzare metodi di contraccezione non ormonali efficaci (metodo di barriera in associazione a gel spermicida o sterilizzazione chirurgica) durante lo studio e per almeno 6 mesi dopo la sospensione del trattamento in studio. 11. Aspettativa di vita di almeno 12 settimane.
    E.4Principal exclusion criteria
    1. Previous systemic non-hormonal anticancer therapy in the metastatic or locally advanced breast cancer setting. 2. Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting. 3. Disease progression while receiving trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting. 4. Disease-free interval from completion of adjuvant or neo-adjuvant systemic non-hormonal treatment to recurrent disease of less than 6 months. 5. History of persistent Grade 2 or higher (NCI-CTC, Version 4.0) hematological toxicity resulting from previous adjuvant or neoadjuvant therapy. 6. Radiographic evidence of central nervous system (CNS) metastases as assessed by computed tomography (CT) or magnetic resonance imaging (MRI). 7. Current peripheral neuropathy of Grade 3 or greater (NCI-CTC, Version 4.0). 8. History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma. 9. Serious uncontrolled concomitant disease that would contraindicate the use of any of the investigational drugs used in this study or that would put the patient at high risk for treatment-related complications. 10. Inadequate organ function, evidenced by the following laboratory results: • Absolute neutrophil count <1,500 cells/mm3 • Platelet count <100,000 cells/mm3 • Hemoglobin <9 g/dL • Total bilirubin greater than upper limit of normal (ULN) (unless the patient has documented Gilbert's syndrome) • Aspartate aminotransferase AST; SGOT) or alanine aminotransferase (ALT; SGPT) >2.5 × ULN • AST (SGOT) or ALT (SGPT) >1.5 × ULN with concurrent serum alkaline phosphatase >2.5 × ULN; Serum alkaline phosphatase may be >2.5 × ULN only if bone metastases are present and AST (SGOT) and ALT (SGPT) <1.5 × ULN • Serum creatinine >2.0 mg/dL or 177 μmol/L • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic coagulation) 11. Uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident (CVA)/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) Grade II or higher, or serious cardiac arrhythmia requiring medication. 12. Current known infection with HIV, HBV, or HCV. 13. Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy. 14. Major surgical procedure or significant traumatic injury within 28 days prior to enrollment into the study or anticipation of need for major surgery during the course of study treatment. 15. Receipt of intravenous (IV) antibiotics for infection within 14 days prior to enrollment into the study. 16. Current chronic daily treatment with corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. Et al.
    I pazienti che soddisfano uno qualsiasi dei seguenti criteri di esclusione non saranno ritenuti idonei a prendere parte a questo studio. Le valutazioni devono essere condotte in base alle tempistiche previste dal Calendario delle valutazioni. 1. Precedente terapia antineoplastica sistemica non ormonale per il tumore mammario metastatico o localmente avanzato. 2. Precedente assunzione di agenti anti-HER-2, approvati o sperimentali, per il trattamento di un qualsiasi tumore mammario, eccetto trastuzumab e/o lapatinib nel contesto neoadiuvante o adiuvante. 3. Progressione della malattia in corso di terapia con trastuzumab e/o lapatinib nel contesto adiuvante o neoadiuvante. 4. Intervallo libero da malattia inferiore a 6 mesi dal completamento della terapia sistemica non ormonale, adiuvante o neoadiuvante, alla recidiva. 5. Anamnesi di tossicità ematologica persistente di grado 2 o superiore (NCI-CTC, Versione 4.0) derivante da precedente terapia adiuvante o neoadiuvante. 6. Evidenza radiografica di metastasi a carico del sistema nervoso centrale (SNC), rilevate tramite tomografia computerizzata (TC) o risonanza magnetica (RM). 7. Neuropatia periferica in atto di grado 3 o superiore (NCI- CTC, Versione 4.0). 8. Anamnesi di altre neoplasie maligne manifestatesi negli ultimi 5 anni, ad eccezione di carcinoma cervicale in situ o carcinoma basocellulare. 9. Grave patologia concomitante non adeguatamente controllata che renderebbe controindicato l'uso di qualsiasi farmaco sperimentale utilizzato in questo studio o che porrebbe il paziente ad alto rischio di sviluppare complicanze correlate al trattamento. 10. Inadeguata funzione d'organo, attestata dai seguenti risultati di laboratorio: • Conta assoluta dei neutrofili &lt; 1.500 cellule/mm3 • Conta piastrinica &lt; 100.000 cellule/mm3 • Emoglobina &lt; 9 g/dl • Bilirubina totale maggiore del limite superiore della norma (ULN) (a meno che il paziente presenti una sindrome di Gilbert documentata) • Aspartato aminotransferasi (AST, SGOT) o alanina aminotransferasi (ALT, SGPT) &gt; 2,5 x ULN • AST (SGOT) o ALT (SGPT) &gt; 1,5 × ULN con concomitante fosfatasi alcalina sierica &gt; 2,5 × ULN. La fosfatasi alcalina sierica può essere &gt; 2,5 × ULN soltanto in presenza di metastasi ossee e di valori di AST (SGOT) e ALT (SGPT) &lt; 1,5 × ULN • Creatinina sierica &gt; 2,0 mg/dl o 177 μmol/l • Rapporto internazionale normalizzato (INR) e tempo di tromboplastina parziale attivata (aPTT) o tempo di tromboplastina parziale (PTT) &gt; 1,5 × ULN (eccetto pazienti in coagulazione terapeutica) 11. Ipertensione non adeguatamente controllata (sistolica &gt; 150 mm Hg e/o diastolica &gt; 100 mm Hg) o patologia cardiovascolare clinicamente significativa (ossia attiva): accidente cerebrovascolare (CVA)/ictus o infarto del miocardio nei 6 mesi precedenti la prima somministrazione del farmaco in studio, angina instabile, insufficienza cardiaca congestizia (CHF) di classe NYHA (New York Heart Association) II o superiore, oppure grave aritmia cardiaca che richieda trattamento farmacologico. 12. Nota infezione in atto da HIV, HBV o HCV. 13. Dispnea a riposo dovuta a complicanze di una neoplasia maligna in stadio avanzato o di altra patologia, con necessità di ossigenoterapia continua. 14. Intervento di chirurgia maggiore o lesione traumatica significativa nei 28 giorni precedenti l'arruolamento nello studio, oppure previsione della necessità di ricorrere a un intervento di chirurgia maggiore durante il trattamento in studio. 15. Terapia con antibiotici per via endovenosa (EV) per un'infezione nei 14 giorni precedenti l'arruolamento nello studio. 16. Trattamento giornaliero cronico in atto con corticosteroidi (dose maggiore di 10 mg/die di metilprednisolone o equivalente), con l’esclusione degli steroidi per via inalatoria. Et al.
    E.5 End points
    E.5.1Primary end point(s)
    ORR assessed by IRC according to RECIST version 1.1, based on the best (confirmed) overall response (BOR).
    L'analisi dell'endpoint primario (ORR valutato dall'IRC in base ai criteri RECIST, versione 1.1) si basa sulla miglior risposta globale (confermata) (BOR).
    E.5.1.1Timepoint(s) of evaluation of this end point
    When all patients have progressed, have been followed up for at least 24 months after the last patient is enrolled into the corresponding cohort, discontinued study medication, withdrawn consent from the study, or died, whichever occurs first.
    L'analisi finale della OS sarà condotta quando tutti i pazienti saranno stati sottoposti a un follow-up di almeno 24 mesi dopo l'arruolamento dell'ultimo paziente nella coorte corrispondente, interruzione del farmaco, revoca del consenso o decesso, a seconda di quale delle ipotesi si verifichi per prima.
    E.5.2Secondary end point(s)
    • BOR as assessed by the investigator • Time to and duration of response (in responders) as assessed by the Investigator and IRC • PFS • TTP • OS
    BOR valutata dallo sperimentatore, tempo alla risposta e durata della risposta (nei soggetti responsivi) valutati dallo sperimentatore e dall’IRC, PFS, TTP e OS.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Final analysis of PFS and TTP, and the first analysis of OS will be performed at the time of the final analysis of BOR. The final analysis of OS will take place when all patients have been followed up for at least 24 months after the last patient is enrolled into the corresponding cohort, unless they have been lost to follow-up, withdrawn consent, or died, or if the study is prematurely terminated by the Sponsor, whichever occurs first.
    L’analisi finale di PFS e TTP e la prima analisi di OS saranno condotte insieme all'analisi finale di BOR. L'analisi finale di OS sarà condotta quando tutti i pazienti saranno stati sottoposti a un follow-up di almeno 24 mesi dopo l'arruolamento dell'ultimo paziente nella coorte corrispondente, eccetto nei casi di perdita al follow-up, revoca del consenso o decesso, oppure di interruzione prematura dello studio per decisione dello sponsor, a seconda di quale delle ipotesi si verifichi per prima.
    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
    Quality of life, tolerability, optional translational research
    Qualità della vita, progetto opzionale di ricerca traslazionale
    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 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 concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA57
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Brazil
    United States
    E.8.7Trial has a data monitoring committee Yes
    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 study will end when all patients have been f.u. for at least 24 m. after the last patient is enrolled into the corresponding cohort, unless they have been lost to f.u., withdrawn consent, or died, or if the study is stopped by Sponsor
    Lo studio terminerà quando tutti i pazienti saranno stati sottoposti a f.u. di almeno 24 mesi dopo l'arruolamento dell'ultimo paziente nella rispottiva coorte, a meno di perdita di f.u., ritiro consenso, morte o interruzione da parte dello Sponsor
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months42
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months42
    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.1.1Number of subjects for this age range: 0
    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: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 110
    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 No
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 161
    F.4.2.2In the whole clinical trial 210
    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)
    Patients who discontinue study treatment for progressive disease or
    other reasons will receive treatment according to the local standard of
    care. Any post-study anticancer therapies, information on patient
    outcomes, and information on post-progression anticancer therapies
    will be recorded in the eCRF during the study follow-up period as
    reasonably possible.
    I pazienti che interromperanno il trattamento per progressione o altre ragioni, riceveranno il trattamento in accordo allo standard of care. Ogni terapia antitumorale dopo lo studio, informazione sulle risposte del paziente e informazione sulle terapie antitumorali dopo la progressione saranno registrate nella eCRF durante il periodo di follow up dello studio se possibile.
    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 Decision2012-02-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-01-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-10-15
    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