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   38470   clinical trials with a EudraCT protocol, of which   6318   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:2010-022620-77
    Sponsor's Protocol Code Number:AB10006
    National Competent Authority:Slovakia - SIDC (Slovak)
    Clinical Trial Type:EEA CTA
    Trial Status:Prohibited by CA
    Date on which this record was first entered in the EudraCT database:2015-04-09
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSlovakia - SIDC (Slovak)
    A.2EudraCT number2010-022620-77
    A.3Full title of the trial
    A prospective, multicentre, open-label, randomised, uncontrolled, phase 1/2 study to evaluate efficacy and safety of masitinib in combination with etoposide, or masitinib in combination with irinotecan in patients with advanced hepatocellular carcinoma and who relapsed after a first line therapy with sorafenib.
    Prospektívna, multicentrická, otvorená, randomizovaná, nekontrolovaná, štúdia fázy 1/2, k zhodnoteniu účinnosti a bezpečnosti masitinibu v kombinácii s etoposidom, alebo masitinibu v kombinácii s irinotekanom pre pacientov s pokročilým hepatocelulárnym karcinómom, ktorí relabovali po prvej línii liečby sorafenibom.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Evaluation of safety and efficacy of masitinib combined with etoposide or irinotecan in patients with relapsing liver cancer
    Zhodnotenie bezpečnosti a účinnosti masitinibu v kombinácii s etoposidom alebo irinotekanom u pacientov s opatovným výskytom rakoviny pečene
    A.4.1Sponsor's protocol code numberAB10006
    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 SponsorAB Science
    B.1.3.4CountryFrance
    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 supportAB Science
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAB Science
    B.5.2Functional name of contact pointValérie Brakni
    B.5.3 Address:
    B.5.3.1Street Address3 avenue George V
    B.5.3.2Town/ cityParis
    B.5.3.3Post code75008
    B.5.3.4CountryFrance
    B.5.4Telephone number+ 33 1 47 20 66 76
    B.5.5Fax number0147202411
    B.5.6E-mailvalerie.brakni@ab-science.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 namemasitinib
    D.3.2Product code AB1010
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNmasitinib mesylate
    D.3.9.1CAS number 790-29979-5
    D.3.9.2Current sponsor codeAB1010
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNmasitinib mesylate
    D.3.9.1CAS number 790-299-79-5
    D.3.9.2Current sponsor codeAB1010
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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: 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 Toposar®, VePesid®, Etopophos®
    D.2.1.1.2Name of the Marketing Authorisation holderTEVA SANTE
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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 nameetoposide
    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 INNETOPOSIDE PHOSPHATE
    D.3.9.1CAS number 117091642
    D.3.9.3Other descriptive nameETOPOSIDE PHOSPHATE
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNETOPOSIDE PHOSPHATE
    D.3.9.1CAS number 117091642
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number45
    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: 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 Camptosar
    D.2.1.1.2Name of the Marketing Authorisation holderPFIZER HOLDING FRANCE
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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 nameirinotecan
    D.3.4Pharmaceutical form Solution for injection
    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 INNIRINOTECAN
    D.3.9.1CAS number 97682445
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number180
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIRINOTECAN
    D.3.9.1CAS number 97682445
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number135
    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
    Hepatocellular carcinoma
    Hepatocelulárny karcinóm
    E.1.1.1Medical condition in easily understood language
    Hepatic cancer
    Rakovina pečene
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level LLT
    E.1.2Classification code 10019829
    E.1.2Term Hepatocellular carcinoma recurrent
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level LLT
    E.1.2Classification code 10019828
    E.1.2Term Hepatocellular carcinoma non-resectable
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level LLT
    E.1.2Classification code 10019830
    E.1.2Term Hepatocellular carcinoma resectable
    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
    Overall Survival (OS)
    Celkové prežitie (OS)
    E.2.2Secondary objectives of the trial
    • Survival rate at week 6, 12, 18, 24 and every 12 weeks after
    • Overall Progression Free Survival (PFS) according to RECIST version 1.1 and according to Modified RECIST (mRECIST) assessment for hepatocellular carcinoma
    • PFS rate at week 6, 12, 18, 24 and every 12 weeks after, according to RECIST version 1.1. and to mRECIST assessment for hepatocellular carcinoma
    • Tumour assessment, first according to RECIST version 1.1. and secondly according to mRECIST assessment for hepatocellular carcinoma:
    o Overal Time to progression (TTP)
    o TTP rate at week 6, 12, 18, 24 and every 12 wks after
    o Objective response rate (CR + PR) at week 6, 12, 18, 24 and every 12 weeks after
    o Control disease rate (CR + PR + SD) at week 6, 12, 18, 24 and every 12 weeks after
    o Best response during study treatment
    o Alpha fetoprotein dosage at week 6, 12, 18, 24 and every 12 weeks after
    • Safety profile using the NCI CTC v4.02 classification
    • Pharmacokinetics
    • Phenotypic Analysis of selected genes
    • Miera prežitia v týždňoch 6, 12, 18, 24 a potom každých 12 týždňov
    • Celková miera prežitia bez progresie ochorenia (PFS) vzhľadom k RECIST verzie 1.1 a vzhľadom k modifikovanému RECIST (mRECIST) hodnoteniu hepatocelulárnych karcinómov
    • Hodnotenie nádoru, najprv podľa RECIST verzie 1.1 a sekundárne podľa mRECIST hodnotenia hepatocelulárnych karcinómov:
    o Celkový čas do progresie
    o Miera TTP v týždňoch 6, 12, 18, 24 a potom každých 12 týždňov
    o Objektívna škála odpovedi (CR+PR) v týždňoch 6, 12, 18, 24 a potom každých 12 týždňov
    o Najlepšia odozva počas liečby
    o Hladina alfa-fetoproteínu v týždňoch 6, 12, 18, 24 a potom každých 12 týždňov
    o Bezpečnostný profil pomocou klasifikácie NCI CTC v4.02
    o Farmakokinetika
    o Analýza fenotypov vybraných génov

    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. histologically or cytologically confirmed advanced-stage hepatocellular carcinoma (HCC) (unresectable, and/or metastatic) or responding to the Barcelona diagnostic criteria
    2. Patient who has received sorafenib single agent as 1st line treatment and had discontinued from this treatment for any reason (ie, tumor disease progression, intolerance) at least 14 days prior to baseline (A line of treatment is defined as at least 1 prior therapeutic regimen consisting of chemotherapy or biologic agent). Requirement for sorafenib treatment is not applicable to patients who have not been previously treated with sorafenib for any reason (e.g., contra-indication to sorafenib, patient refusal to sorafenib treatment due to expected toxicity, etc.)
    3. Patient who has recovered from any significant sorafenib-related treatment toxicities prior to baseline (≤Grade 2)
    4. Patient with at least 1 untreated target lesion that could be measured in 1 dimension:
    • according to the RECIST 1.1
    • and according to Modified RECIST assessment for hepatocellular carcinoma
    5. Patient who has received local therapy prior to sorafenib administration (surgery, hepatic arterial embolization, chemoembolization, radioembolisation, radiofrequency ablation, percutaneous ethanol injection or cryoablation) are eligible. Local therapy must be completed at least 4 weeks prior to the baseline scan
    6. Adequate antiviral systemic therapy in symptomatic and asymptomatic HBV Ag carriers
    7. Patient eligible for receiving etoposide and irinotecan (either as a 2nd line treatment after sorafenib or 1st line for patient not previously treated with sorafenib)
    8. Child-Pugh liver function class A
    9. Barcelona Clinic Liver Cancer classification: class C
    10. ECOG Performance Status ≤ 2
    11. Patient with adequate organ function:
    • A N C ≥ 1.5 x 109/L
    • Hb ≥ 10 g/dL
    • Platelets ≥ 75 x 109/L
    • AST/ALT ≤ 5 x ULN
    • Gamma-GT ≤ 5 x ULN
    • Total bilirubin ≤ 3 x ULN
    • Normal Creatinine or if abnormal creatinine, creatinine clearance ≥ 50 mL/min (Cockcroft and Gault formula)
    • Albumin ≥ 0.75 x LLN
    • Urea < 2 x ULN
    • Proteinuria < 30 mg/mL (1+) on the dipstick. If proteinuria is ≥ 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hour
    12. Patient with life expectancy > 3 months
    13. ≥ 18 years
    14. weight > 40 kg and BMI > 18 kg/m²
    15. Female patient of childbearing potential, who agrees to use 2 highly effective methods (1 for the patient and 1 for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. Acceptable forms of contraception include:
    • A documented placement of an IUD or IUS and the use of a barrier method used with spermicidal
    foam/gel/film/cream/suppository)
    • Documented tubal ligation (female sterilization). In addition, a barrier method should also be used
    • Double barrier method: Condom and occlusive cap with spermicidal foam/gel/film/cream/suppository
    • Any other contraceptive method with a documented failure rate of <1% per year
    • Abstinence
    Male patients must use medically acceptable methods of contraception if your female partner is pregnant, from the time of the 1st administration of the study drug until 3 months following administration of the last dose of study drug. Acceptable methods include:
    • Condom;
    • If you have undergone surgical sterilization (vasectomy with documentation of azoospermia) a condom should also be used.
    Male patients must use 2 highly effective methods (1 for the patient and 1 for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. The acceptable methods of contraception are as follows:
    • Condom and occlusive cap with spermicidal foam/gel/film/cream/suppository;
    • Surgical sterilization and a barrier method (condom or occlusive cap used with spermicidal foam/gel/film/cream/suppository);
    • Your female partner uses oral contraceptives, injectable progesterone or subdermal implants and a barrier method
    • Medically prescribed topically-applied transdermal contraceptive patch and a barrier method
    • Your female partner has undergone documented tubal ligation (female sterilization). In addition, a barrier method should also be used;
    • Your female partner has undergone documented placement of an IUD or IUS and the use of a barrier method used with spermicidal foam/gel/film/cream/suppository);
    • Abstinence.
    16. Patient able and willing to comply with study visits and procedures
    17. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed.
    18. Patient affiliated to a social security regimen
    19. Patient able to understand and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity druing the first 2 months of treatment.
    1. Pacient s histologicky alebo cytologicky potvrdeným pokročilým hepatocelulárnym karcinómom (HCC) (neresekovateľného, a/alebo metastatického) alebo reagujúcim na barcelónske diagnostické kritériá
    2. Pacient, ktorý užíval monoterapiu sorafenibom ako prvú líniu liečby a prerušil ju z akéhokoľvek dôvodu (napr. progresia rakoviny, intolerancia) aspoň 14 dní pred zaraďujúcou návštevou (línia liečby je definovaná ako aspoň jedna terapeutická fáza skladajúca sa z chemoterapie alebo biologického činiteľa). Požiadavky pre liečbu sorafenibom nie sú aplikovateľné na pacientov, ktorí neboli v minulosti liečení sorafenibom z akýchkoľvek príčin (napr. kontraindikácia na sorafenib, pacientovo odmietnutie sorafenibu z dôvodu predpokladanej toxicity a ďalšie)
    3. Pacient, ktorý sa zotavil z akýchkoľvek signifikantných prejavov toxicity súvisiacich so sorafenibom pred zaraďujúcou návštevou (≤ Trieda 2)
    4. Pacienti s aspoň jednou neliečenou cieľovou léziou, ktorá môže byť jednorozmerne zmeraná:
    • podľa Odpoveď hodnotiaca kritériá v solídnych tumoroch (RECIST 1.1)
    • a podľa modifikovaného RECIST (mRECIST) hodnotenia pre hepatocelulárny karcinóm
    5. Pacient, ktorý bol liečený lokálnou liečbou pred podaním sorafenibu (operácia, hepatická arteriálna embolizácia, chemoembolizácia, radioembolizácia, radiofrekvenčná ablácia, perkutánne etanolové injekcie (PEI) alebo kryoablácia). Lokálna terapia musí byť ukončená aspoň 4 týždne pred zaraďujúcou návštevou.
    6. Adekvátna antivírová systemická liečba u symptomatických a asymptomatických HBV Ag prenášačov.
    7. Pacienti vhodní pre príjem etoposidu a irinotekanu (buď ako druhú líniu liečby po sorafenibe, alebo ako prvú líniu liečbu pre pacientov predtým neliečených sorafenibom)
    8. Child-Pughova funkcia pečene triedy A
    9. Barcelonská klinická klasifikácia rakoviny pečene (BCLC): trieda C
    10. Eastern Cooperative Oncology Group (ECOG) výkonnostný stav ≤ 2
    11. Pacient s odpovedajúcou funkciou orgánov:
    • Absolútny počet neutrofilov (ANC) ≥ 1.5 x 109/L
    • Hemoglobín ≥ 10 g/dL
    • Trombocyty (PTL) ≥ 75 x 109/L
    • AST/ALT ≤ 5 x ULN
    • Gamma-GT ≤ 5 x ULN
    • Celkový bilirubín ≤ 3x ULN
    • Normálna hodnota kreatinínu alebo, pokiaľ je kreatinín abnormálny, clearance kreatinínu ≥ 50 mL/min (vzorec Cockcrofta a Gaulta)
    • Albumín > 0.75 x LLN
    • Proteinúria < 30 mg/mL (1+) na testovacom prúžku. Pokiaľ je proteinúria na testovacom prúžku ≥1+, proteinúria za 24 hodín musí byť < 1.5g/24 hodín
    12. Pacient s očakávanou dĺžkou života > 3 mesiace
    13. Muži alebo ženy ≥ 18 let
    14. Váha pacienta > 40 kg a BMI > 18 kg/m²
    15. Žena v plodnom veku (vstupujúca do štúdie po menštruácii s negatívnym tehotenským testom), ktorá súhlasí s použitím dvoch metód (jednej pre pacientku a druhej pre partnera) lekársky prijateľných foriem antikoncepcie počas štúdie a po dobu 3 mesiacov po poslednom užití študijného lieku:
    • Dokumentované zavedenie vnútromaternicového telieska (IUD) alebo vnútromaternicového systému (IUS) alebo použitie bariérového spôsobu ochrany (kondóm alebo pesar [diafragma alebo cervikálny klobúčik] v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi).
    • Dokumentované podviazanie vaječníkov (ženská sterilizácia). Okrem toho by mal byť tiež používaný bariérový spôsob ochrany (kondóm alebo pesar [diafragma alebo cervikálny klobúčik] v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi).
    • Dvoj bariérová metóda: Kondóm a okluzívny kryt diafragma alebo cervikálny klobúčik) v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi
    • Akékoľvek iné metódy antikoncepcie so zdokumentovanou mierou zlyhania < 1 % za rok
    • Abstinencia iba pokiaľ sa jedná o obvyklý a preferovaný spôsob života pacientky
    16. Mužskí pacienti musia používať lekársky prijateľné formy antikoncepcie, pokiaľ je ich partnerka tehotná, alebo od doby prvého podania hodnoteného prípravku až do troch mesiacov po poslednej dávke skúšaného lieku. Prijateľné formy sú:
    • kondóm
    • chirurgická sterilizácia (vasektómia so zdokumentovanou azoospermiou) , je treba používať aj kondóm
    Mužskí pacienti musia počas štúdie a 3 mesiace po poslednej liečbe používať dve metódy lekársky prijateľnej vysoko účinnej antikoncepcie (jednu pacient a druhú partnerka). Prijateľné formy antikoncepcie sú:
    • kondóm alebo pesar (diafragma alebo cervikálny klobúčik) v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi.
    • chirurgická sterilizácia (vasektómia so zdokumentovanou azoospermiou) a bariérový spôsob ochrany (kondóm alebo pesar [diafragma alebo cervikálny klobúčik] v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi).
    • Vaša partnerka používa perorálnu antikoncepciu (kombinované tablety s estrogénom či progesterónom), injekcie progesterónu či podkožné implantáty a bariérový spôsob ochrany (kondóm alebo pesar [diafragma alebo cervikálny klobúčik] v kombinácii so spermicídnou penou/gélom/krémom/čiapikmi).





    E.4Principal exclusion criteria
    1. Patient intolerant to etoposide or irinotecan
    2. Patient who has received a liver transplant
    3. Patient with clinically significant symptoms of hepatic encephalopathy
    4. Patient who has previously received more than two line of systemic therapy. One previous therapy must at least be with sorafenib monotherapy unless the patient has not been treated with sorafenib for any reason (e.g. contra-indication to sorafenib, patient refusal to sorafenib due to expected toxicity, etc.) (See Inclusion Criterion 2). Patients participating in surveys or observational studies are eligible to participate in this study.
    5. Patient with previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 5 years prior to entry is permitted
    6. Patient presenting with cardiac disorders defined by at least one of the following conditions:
    • Patient with recent cardiac history (within 6 months) of:
    - Acute coronary syndrome
    - Acute heart failure (class III or IV of the NYHA classification)
    - Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
    • Patient with cardiac failure class III or IV of the NYHA classification
    • Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
    • Syncope without known aetiology within 3 months
    • Uncontrolled severe hypertension, according to the judgement of the investigator, or symptomatic hypertension
    7. Pregnant or nursing female patient
    8. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
    9. Patient with history of poor compliance, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent.
    WASH OUT
    10. Patient treated with any investigational agent within 4 weeks prior baseline
    11. Patient who has had treatment with any of the following within the specified timeframe prior to baseline:
    • Any sorafenib within the 14 days prior to baseline
    • Major surgery within the 4 weeks prior to baseline
    • Any transfusion, treatment with blood component preparation, received erythropoietin, albumin preparation, and granulocyte colony-stimulating factor (G CSF) within the 2 weeks prior to baseline
    1. Pacient je intolerantný na etoposid alebo irinotekan
    2. Pacient podstúpil transplantáciu pečene
    3. Pacient s klinicky signifikantnými príznakmi hepatickej encefalopatie
    4. Pacient, ktorý už predtým prešiel dvomi líniami systematickej liečby. Jedna predchádzajúca liečba musí byť aspoň sorafenibová monoterapia, pokiaľ už pacient nebol predtým z akéhokoľvek dôvodu liečený sorafenibom (napr. kontraindikácia na sorafenib, pacientovo odmietnutie sorafenibu z dôvodu možnej toxicity atd.) (viď zaraďovacie kritériá 2). Pacienti zúčastniaci sa prieskumov alebo pozorovacích štúdií sa môžu zúčastniť tejto štúdie.
    5. Pacienti s predošlým alebo súbežným rakovinovým ochorením, ktoré sa líšia v primárnej lokalite, alebo histológii oproti HCC, OKREM cervikálneho karcinómu in situ, liečeného karcinómu bazálnych buniek, povrchových nádorov močového mechúra (Ta, Tis & T1). Je povolená akákoľvek rakovina medicínsky vyliečená > 5 let pred vstupom do štúdie.
    6. Pacient trpiaci srdcovými chorobami definovanými aspoň jednou z nasledujúcich podmienok:
    • Pacient s nedávnou anamnézou srdcovej príhody (počas posledných 6 mesiacov):
    - Akútny koronárny syndróm
    - Akútne zlyhania srdca (trieda III alebo IV podľa NYHA klasifikácie)
    - Výrazná srdcová arytmia (pretrvávajúca komorová tachykardia, fibrilácia komôr, resuscitovaná náhla srdcová smrť)
    • Pacient so srdcovým zlyhaním triedy III alebo IV podľa NYHA klasifikácie
    • Pacient so závažnými poruchami vodivosti, ktorým sa nedá zabrániť permanentnou reguláciou srdcového rytmu (atrioventrikulárna blokáda II. a III. stupňa, sinoatriálna blokáda).
    • Synkópa bez známej etiológie počas posledných 3 mesiacov.
    7. Tehotná alebo dojčiaca pacientka
    8. Pacient s aktívnou metastázou do centrálneho nervového systému (CNS) alebo s históriou CNS metastáz
    9. Pacient s históriou zlej spolupráce alebo súčasným či minulým psychiatrickým ochorením, ktoré by mohlo narušiť dodržiavanie protokolu štúdie, alebo poskytnutie informovaného súhlasu

    WASH-OUT (VYMÝVANIE) OBDOBIE PREDCHÁDZAJÚCEJ LIEČBY
    10. Pacient liečený akýmkoľvek študijným prípravkom počas posledných 4 týždňov predchádzajúcich zaraďujúcej návšteve
    11. Pacient, ktorý bol liečený akoukoľvek z nasledujúcich medikácií počas špecifikovanej doby pred zaraďujúcou návštevou:
    • Akýkoľvek sorafenib počas 14 dní pred zaraďujúcou návštevou
    • Rozsiahly chirurgický zákrok počas 4 týždňov pred zaraďujúcou návštevou
    • Akákoľvek transfúzia, liečba preparátom s krvnými komponentami, erytropoetín, albumínové preparáty, a faktory stimulujúce kolónie granulocytov (G CSF) počas dvoch týždňov pred zaraďujúcou návštevou.
    E.5 End points
    E.5.1Primary end point(s)
    Overall Survival (OS) defined as the time from randomisation to the date of death from any cause
    Celkové prežitie (OS) definované ako čas od randomizácie do dátumu úmrtia z akejkoľvek príčiny
    E.5.1.1Timepoint(s) of evaluation of this end point
    from randomisation to the date of death from any cause
    od randomizácie do dátumu úmrtia z akejkoľvek príčiny
    E.5.2Secondary end point(s)
    - Survival rate at week 6, 12, 18, 24 and every 12 weeks
    - Overall PFS according to Modified RECIST (mRECIST) assessment for hepatocellular carcinoma
    - PFS rate at week 6, 12, 18, 24 and every 12 weeks according to RECIST version 1.1. and to mRECIST assessment for hepatocellular carcinoma
    - Tumour assessment, first according to RECIST version 1.1. and secondly according to mRECIST assessment for hepatocellular carcinoma:
    - Overall Time to progression (TTP)
    - Objective response rate (CR + PR) at week 6, 12, 18, 24 and every 12 weeks
    - Control disease rate (CR + PR + SD) at week 6, 12, 18, 24 and every 12 weeks
    - Best response during study treatment
    - Alpha fœto protein dosage at week 6, 12, 18, 24 and every 12 weeks
    - Safety profile using the NCI CTC v4.02 classification
    - Pharmacokinetics
    - Phenotypic analysis
    • Miera prežitia v týždňoch 6, 12, 18, 24 a potom každých 12 týždňov
    • Celková miera prežitia bez progresie ochorenia (PFS) vzhľadom k RECIST verzie 1.1 a vzhľadom k modifikovanému RECIST (mRECIST) hodnoteniu hepatocelulárnych karcinómov
    • Hodnotenie nádoru, najprv podľa RECIST verzie 1.1 a sekundárne podľa mRECIST hodnotenia hepatocelulárnych karcinómov:
    o Celkový čas do progresie
    o Miera TTP v týždňoch 6, 12, 18, 24 a potom každých 12 týždňov
    o Objektívna škála odpovedi (CR+PR) v týždňoch 6, 12, 18, 24 a potom každých 12 týždňov
    o Najlepšia odozva počas liečby
    o Hladina alfa-fetoproteínu v týždňoch 6, 12, 18, 24 a potom každých 12 týždňov
    o Bezpečnostný profil pomocou klasifikácie NCI CTC v4.02
    o Farmakokinetika
    o Analýza fenotypov vybraných génov

    E.5.2.1Timepoint(s) of evaluation of this end point
    W6, W12, W18, W24 and every 12 weeks
    T6, T12, T18, T24 a každých 12 týždňov
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    safety and pharmacokinetic
    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 Yes
    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 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 concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    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
    Czech Republic
    Greece
    Slovakia
    Spain
    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
    Patient could be treated until disease progression without clinical benefit confirmed on CT scan by RECIST version 1.1 and Modified RECIST (mRECIST) assessment for hepatocellular carcinoma, limiting toxicity, or consent withdrawal
    Pacient može byť liečený do progresie choroby bez klinického prínosu potvrdeného CT snímkom podľa RECIST verzie 1.1 a Modifikovaného RECIST (mRECIST) hodnotenia pre hepatocelulárny karcinóm, limitujúcej toxicity, alebo odvolania súhlasu pacienta
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number 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: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 16
    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 state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 18
    F.4.2.2In the whole clinical trial 36
    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)
    NOT DIFFERENT
    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 Decision2015-03-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-03-30
    P. End of Trial
    P.End of Trial StatusProhibited by CA
    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