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    Summary
    EudraCT Number:2011-003574-84
    Sponsor's Protocol Code Number:NP27884
    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:2012-03-02
    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 number2011-003574-84
    A.3Full title of the trial
    A Randomized, Placebo-controlled, Double-blind, Multicenter Phase II Trial of Intravenous GC33 at 1600 mg Q2W in Previously Treated Patients with Unresectable Advanced or Metastatic Hepatocellular Carcinoma(HCC).
    Studio randomizzato, controllato con placebo, in doppio cieco, multicentrico di fase II su GC33 somministrato per via endovenosa a un dosaggio 1600 mg Q2W in pazienti precedentemente trattati, affetti da epatocarcinoma avanzato non resecabile o metastatico (HCC)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of intravenous GC33 treatment in patients with liver cancer that cannot be resected or has metastatized and that has not responded to currently available treatment(s).
    Studio sul trattamento di GC33 somministrato per via endovenosa, in pazienti affetti da tumore al fegato non resecabile o metastatico e che non risponde ai trattamente attualmente disponibili.
    A.4.1Sponsor's protocol code numberNP27884
    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 S.p.A
    B.5.2Functional name of contact pointCountry Head - Clin.Ops. Italy
    B.5.3 Address:
    B.5.3.1Street AddressViale G. B. Stucchi 110
    B.5.3.2Town/ cityMonza (MB)
    B.5.3.3Post code20900
    B.5.3.4CountryItaly
    B.5.4Telephone number+39 039 247 5070
    B.5.5Fax number+39 039 247 5084
    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 nameNA
    D.3.2Product code Ro 513-7382/F02
    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.3.8INN - Proposed INNNA
    D.3.9.1CAS number NA
    D.3.9.2Current sponsor codeRO5137382
    D.3.9.3Other descriptive nameNA
    D.3.9.4EV Substance CodeNA
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    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 Yes
    D.3.11.13.1Other medicinal product typeAnticorpo monoclonale
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Second-line treatment for adult patient with unresectable advanced or metastatic hepatocellular cancer.
    Trattamento di seconda linea per pazienti adulti affetti da epatocarcinoma avanzato non resecabile o metastatico
    E.1.1.1Medical condition in easily understood language
    The disease under investigation is advanced liver cancer (hepatocellular
    carcinoma) that cannot be resected, or liver cancer (hepatocellular
    carcinoma) that has metastatized.
    La patologia in studio è il tuomre avanzato del fegato (carcinoma epatocellulare), che non può essere asportato, o cancro del fegato (carcinoma epatocellulare) metastatico.
    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 10019828
    E.1.2Term Hepatocellular carcinoma non-resectable
    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 evaluate efficacy of GC33 vs. placebo through investigator-assessed
    progression-free survival (PFS) in patients with unresectable advanced
    or metastatic hepatocellular carcinoma (HCC) previously treated with at
    least 1 systemic agent, with documented progressive disease, or
    documented adverse event(s) resulting in discontinuance of that (those)
    agents, stratified by level of GPC-3 expression (IHC score)
    Valutare l’efficacia di GC33 verso placebo sulla base della sopravvivenza libera da progressione (PFS) giudicata dallo sperimentatore, in pazienti affetti da epatocarcinoma (HCC) avanzato non resecabile o metastatico, precedentemente trattati con almeno 1 agente sistemico, che presentano una documentata progressione della malattia o documentati eventi avversi che hanno portato all’interruzione di tale/i agente/i, stratificati in base al livello di espressione di GPC-3 (punteggio IHC)
    E.2.2Secondary objectives of the trial
    1. To compare treatment effect of GC33 vs. placebo on overall survival(OS)
    2. To compare treatment effect of GC33 vs. placebo on disease control
    rate
    3. To evaluate the tolerability and safety of GC33 when given as
    monotherapy in comparison to placebo using the NCI-CTCAE version 4.0
    4. To further characterize the pharmacokinetic (PK) profile of GC33
    5. To validate the GPC-3 immunohistochemistry(IHC) assay for analysis of GPC-3 expression
    1. Confrontare l’effetto del trattamento GC33 rispetto al placebo sulla base alla sopravvivenza globale (OS, overall survival)
    2. Confrontare l’effetto del trattamento GC33 rispetto al placebo sulla base al tasso di controllo della malattia e il tempo alla progressione (TTP)
    3. Valutare la tollerabilità e la sicurezza di GC33 quando somministrato come monoterapia in confronto al placebo usando i NCI-CTCAE versione 4.0
    4. Caratterizzare ulteriormente il profilo farmacocinetico di GC33
    5. Convalidare il saggio immunoistichimico (IHC) di GPC-3 per l’analisi dell’espressione di GPC-3
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female ≥18 years old
    2. Life expectancy of at least 12 weeks
    3. ECOG Performance Status of 0 or 1
    4. Histologically confirmed unresectable advanced or metastatic
    hepatocellular carcinoma (without fibrolamellar subtype)
    5. Prior treatment with at least 1 systemic agent, with documented
    progressive disease after systemic agent(s), or documented adverse
    event(s) associated with prior systemic agent(s) that resulted in
    discontinuance of that(those) agent(s)
    6.Not a candidate for curative treatments(e.g.resection, transplantation)
    7. Child-Pugh A (score of 5-6)
    8. Adequate hematologic function: Platelet count ≥ 50x 109/L, Absolute
    Neutrophil Count ≥ 1,500/μL, Hemoglobin ≥ 8.0 g /dL
    9. Adequate hepatic function: ALT (SGPT), AST (SGOT) ≤ 5 x ULN,
    Bilirubin ≤ 2 mg/ dL
    10. Adequate renal function: Serum Creatinine ≤ 2 x ULN or calculated
    Creatinine Clearance ≥ 60 ml/min using Cockcroft and Gault formula
    11. Ability to provide, for central review, a tumor tissue sample
    containing at least 5 % tumor cells to determine the level of GPC-3
    expression by IHC. Determination of GPC-3 expression level is required
    prior to study entry.
    12. Patients must have recovered from effects of any major surgery or
    significant traumatic injury at least 14 days before the first dose of study
    treatment
    13. Measurable disease (by RECIST 1.1) prior to the administration of
    study treatment
    14. Negative serum pregnancy test
    1.Uomo o donna di età ≥ 18
    2.Aspettativa di vita di almeno 12 settimane
    3.Stato di performance ECOG pari a 0 o1
    4.Carcinoma epatocellulare confermato istologicamente (senza sottotipo fibrolamellare)
    5.Precedente trattamento con almeno 1 agente sistemico, con progressione di malattia documentata dopo agente/i sistemico/i o eventi avversi documentati associati al/ai precedente/i agente/i sistemico/i che hanno comportato l’interruzione della somministrazione di tale/i agente/i.
    6.Nessuna candidatura a terapie curative (ad esempio resezione, trapianto)
    7.Classificazione Child-Pugh A (punteggio di 5-6)
    8.Funzione ematologica adeguata:
    -Conta piastrinica &gt; 50x 109/L
    -Conteggio assoluto dei neutrofili &gt;1.500/µL.
    -Emoglobina ≥ 8,0 g/dL
    9.Funzione epatica adeguata:
    -ALT (SGPT) e AST (SGOT) &lt; 5 x ULN
    -Bilirubina &lt;2 mg/ dL
    10.Funzione renale adeguata:
    - Creatinina nel siero ≤ 2 X ULN o Clearance della creatinina ≥ 60 ml/min calcolata usando la formula di Cockcroft and Gault
    11.Capacità di fornire, per la revisione centrale, un campione di tessuto tumorale per determinare il livello di espressione di GPC-3 mediante IHC. La determinazione del livello di espressione di GPC-3 è obbligatoria prima dell’entrata nello studio.
    12.Le condizioni dei pazienti devono essersi ristabilite a seguito di qualsiasi intervento chirurgico importante o significativa lesione traumatica, almeno 14 giorni prima della prima dose del trattamento in studio
    13.Malattia misurabile (secondo i criteri RECIST 1.1) prima della somministrazione del trattamento in studio
    14.Test di gravidanza negativo su siero, eseguito entro 10 giorni prima dell’inizio del dosaggio per le donne in età fertile. Le donne non potenzialmente fertili possono essere incluse se sono chirurgicamente sterili o sono in menopausa da &gt; 1 anno
    E.4Principal exclusion criteria
    1. Child-Pugh B or C
    2. Known HCC with fibro-lamellar histology
    3. Known brain or leptomeningeal metastases
    4. Patients with a previous malignancy within the past 5 years are
    excluded(patients who had curatively treated basal cell carcinoma of the
    skin,early gastrointestinal cancer by endoscopic resection, and/or insitu
    carcinoma of the cervix and other malignancies which were considered
    cured and deemed by the PI to have no impact on the PFS and OS are
    allowed after discussion with the study medical monitor)
    5. Active infectious diseases requiring treatment except for hepatitis B and C
    6. NCI CTCAE version 4.0 grade 3 hemorrhage within 4 weeks of starting
    the study treatment
    7. History of organ allograft including liver transplant
    8. Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
    9. Patient who have had any anticancer treatment within 2 weeks prior to entering the study
    10. Patients who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies
    11. Patients receiving Interferon therapy
    12. Patients with baseline QTc > 470 ms, or patients with baseline
    resting bradycardia <45 beats per minutes.
    13. Patients who received anticoagulation or thrombolytic agents for therapeutic purposes (except for low-dose administration for catheter
    clearance or for prophylactic purposes)
    1.Classificazione Child-Pugh B o C
    2.HCC nota con istologia fibrolamellare
    3.Conosciute metastasi cerebrali o leptomeningee
    4.I pazienti con storie di neoplasia maligna negli ultimi 5 anni sono esclusi (pazienti che hanno avuto carcinoma della pelle a cellule basali trattato in via curativa, tumore gastrointestinale precoce rimosso endoscopicamente, e/o carcinoma in situ della cervice e altre malignità che sono state considerate guarite e ritenute dallo Sperimetatore Principale non avere impatto sulla PFS e sull’OS sono permesse dopo discussione con il Medical Monitor dello studio).
    5.Malattie infettive attive che richiedono una terapia, eccezione fatta per l’epatite B e C
    6.Emorragia di grado 3 secondo i NCI CTCAE versione 4.0 nelle 4 settimane precedenti l’inizio del trattamento dello studio
    7.Anamnesi di trapianto di organo allogenico, tra cui trapianto di fegato
    8.Somministrazione prevista o in corso di una terapia antitumorale diversa da quella somministrata in questo studio
    9.Pazienti che sono stati sottoposti a un trattamento anticancro nelle 2 settimane precedenti l’inizio dello studio
    10.Pazienti che non si sono completamente ristabiliti da tossicità associate a precedenti terapie locoregionali o sistemiche per l’HCC.
    11.Pazienti che ricevono una terapia con interferone a dosi elevate
    12.Pazienti con Tc &gt; 470 ms al baseline, o pazienti con bradicardia a riposo &lt;45 battiti al minuto al baseline
    13.Pazienti cui sono stati somministrati agenti anticoagulanti o trombolitici a scopo terapeutico (eccezione fatta per la somministrazione a basso dosaggio per la clearance del catetere o a scopi profilattici) nelle 2 settimane precedenti il Giorno 1
    E.5 End points
    E.5.1Primary end point(s)
    Progression-free survival
    Sopravvivenza libera da progressione (PFS)
    E.5.1.1Timepoint(s) of evaluation of this end point
    When PFS data mature (about 24 months from FPFV)
    Quando saranno disponibili i dati di sopravvivenza libera da progressione (circa 24 mesi dopo la randomizzazione del primo paziente).
    E.5.2Secondary end point(s)
    Overall survival
    Time to progression
    Disease control rate
    Sopravvivenza globale (OS)
    Tempo alla progressione (TTP)
    Tasso di controllo della malattia (DCR)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Planned at the same time as primary endpoint
    Pianificata allo stesso tempo dell'end point primario
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number 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 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 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
    Hong Kong
    Japan
    Korea, Democratic People's Republic of
    Korea, Republic of
    New Zealand
    Singapore
    Taiwan
    United States
    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 study will continue until the last data point from the last patient (Overall Survival) is received, 12 months after the last patient was enrolled, or all patients completed the 28-day follow-up visit, whichever comes later.
    Lo studio continuerà fino alla ricezione dell’ultima informaz.ultimo paziente(OS),12 mesi dopo l’arruolamento dell’ultimo paz. o dopo che tutti i paz.hanno completato la visita di follow-up del 28°giorno, secondo l’evento che si verifica per ultimo.
    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 months32
    E.8.9.1In the Member State concerned 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: 78
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 78
    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 state24
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 62
    F.4.2.2In the whole clinical trial 156
    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)
    A subject who has ended his/her participation in the trial will be
    followed for 28 days for safety and every 8 weeks thereafter for
    survival and collection of information on his/her subsequent anticancer
    therapy(ies).
    Un soggetto che ha concluso la sua partecipazione allo studio sarà seguito per 28 giorni per il monotoraggio della sicurezza e successivamente ogni 8 settimane per la sopravvivenza e la raccolta di informazioni sulla sua successiva terapia antitumorale.
    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 Decision2012-02-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-01-24
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-08-20
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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