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    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   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).

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    Summary
    EudraCT Number:2008-002269-29
    Sponsor's Protocol Code Number:NCT-2007-11-01-1011
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2009-01-27
    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 ConcernedGermany - BfArM
    A.2EudraCT number2008-002269-29
    A.3Full title of the trial
    A prospective, randomized, double-blind, multicenter, Phase III clinical study on transarterial chemoembolisation (TACE) combined with Sorafenib vs. TACE plus placebo in patients with hepatocellular cancer (HCC) before liver transplantation (LTx) – Heidelberg Liver Cancer Study [HEILIVCA STUDY]
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase III Trail of TACE + Sorafenib vs. TACE + Placebo for HCC Patients before Liver Transplantation
    A.3.2Name or abbreviated title of the trial where available
    HeiLivCa
    A.4.1Sponsor's protocol code numberNCT-2007-11-01-1011
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberISRCTN24081794
    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 SponsorUniversitätsklinikum Heidelberg
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBayer Vital GmbH
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversitaetsklinikum Heidelberg / NCT
    B.5.2Functional name of contact pointChirurgie
    B.5.3 Address:
    B.5.3.1Street AddressIm Neuenheimer Feld 210
    B.5.3.2Town/ cityHeidelberg
    B.5.3.3Post code69120
    B.5.3.4CountryGermany
    B.5.4Telephone number+496221566110
    B.5.5Fax number+496221564215
    B.5.6E-mailpeter.schemmer@med.uni-heidelberg.de
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Nexavar 200 mg Filmtabletten
    D.2.1.1.2Name of the Marketing Authorisation holderBayer Health Care AG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEMEA/H/C/690/II/0008
    D.3 Description of the IMP
    D.3.1Product nameNexavar
    D.3.4Pharmaceutical form 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 INNSorafenib
    D.3.9.1CAS number 4750207-59-1
    D.3.9.2Current sponsor codeBAY 43-90006
    D.3.9.3Other descriptive nameNexavar
    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.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    HCC without extrahepatic metastases
    E.1.1.1Medical condition in easily understood language
    Liver Cancer
    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 10027479
    E.1.2Term Metastatic liver carcinoma
    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
    The primary objective of the trial is to determine whether the combination of TACE and Sorafenib (Arm A) in comparison to TACE plus placebo (Arm B) better controls tumor growth within the liver in patients with HCC in terms of Time to Progression (TTP) before curative liver transplantation.
    E.2.2Secondary objectives of the trial
    Secondary objectives are to compare the rates of patients, who reach LTx and the frequencies of TACE treatments required between the 2 arms, to assess safety and toxicity, the progression-free interval, the 1-year and 2-year overall survival, overall response rate, complete response (CR) and partial response (PR), disease control rate (DCR) as well as the health-related quality of life (HQoL) and the influence of the treatment on the AFP-level during the trial. Furthermore it is planned to conduct biomarker studies which examine liver biopsies, whole liver specimen after LTx and serum samples for genetic, gene expression and protein alterations. The biomarker findings will be correlated with clinical parameters.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients with hepatocellular carcinoma (HCC) without extrahepatic disease.
    Inclusion Criteria
    • Patients with HCC without prior therapy, basically eligible for LTx at screening
    HCC diagnosed by histology or per non-invasive European Association for the Study of the Liver (EASL) criteria (only cirrhotic patients):
    1. Radiological criteria: two coincident imaging techniques: Focal lesion > 2 cm with arterial hypervascularization
    2. Combined criteria: one imaging technique associated with alpha-Fetoprotein (AFP): Focal lesion > 2 cm with arterial hypervascularization + AFP levels > 400 ng/ml
    • Pretreatment CT or MRI and bone scan without evidence of radiographically definable vascular invasion or extrahepatic disease not older than 28 days, for bone scans not older than 8 weeks
    • Sufficient hematologic, liver and renal function: Hb>9.0g/%, WBC >3.000cells/mm³ (ANC>1.500cells/mm³), platelets >75.000 cells/mm³, Bilirubin <3mg/dl. Patients should have bilateral renal function, as determined by abdominal CT with serum creatinine <1.5mg/dl and Creatinine clearance (CrCL) >30ml/min in 24h urine or Modification of Diet in Renal Disease Rate (MDRD)
    • PT-INR/PTT <1.5x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists].
    • Performance status: Karnofsky index >70%
    • No acute infections at the time of therapy initiation
    • Patients must sign a study specific informed consent form
    E.4Principal exclusion criteria
    • Residual radiological definable extrahepatic disease, portal vein involvement or lymph node involvement in CT, MRI or bone scan. Patients who are not potentially eligible for LTx are excluded.
    • Patients with prior or concomitant systemic anticancer therapy or local tumor therapy (i.e. LITT; PEI, cryotherapy, RFA), or with prior TACE <= 3 days before randomisation or with concomitant biologic-response modifiers, strong CYP3A4 inhibitors
    • Patients with significant cardiovascular disease such as myocardial infarction <6months previously, chronic heart failure (revised New York Hearth Association (NYHA) grade III-IV) or unstable coronary artery disease
    • Patients with severe pulmonary disease that would be hazardous for LTx
    • Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure >90 mm Hg, despite optimal management
    • Thrombotic or embolic events including transient ischemic attacks within the past 6 months
    • Hemorrhage/bleeding event ≥Grade 3 within 4 weeks of first dose of study drug
    • Patients with contraindication to arterial procedure during TACE (portal or liver vein infiltration, allergy against contrast dye, uncontrolled hyperthyroidism)
    • Patients with previous malignancy other than carcinoma in situ of the skin and the cervix within 5 years prior treatment
    • Patients < 18 years
    • Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial (and men for at least 3 months after last administration of study medication). Women of childbearing potential must agree to practice adequate contraception and to refrain from breastfeeding, as specified in the informed consent.
    • Patients with uncontrolled infections or HIV sero-positive patients
    • History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
    • Mental conditions rendering the patient incapable to understand the nature, scope, and consequences of the study
    • No patient will be allowed to enroll in this study more than once
    • Prior organ transplantation (e.g. renal…)
    • Concomitant immunosuppressive treatment (steroids, mycophenolate mofetil, cyclosporine, temsirolimus, everolimus, tacrolimus, …)
    E.5 End points
    E.5.1Primary end point(s)
    TTP will be compared between Arm A and Arm B using a 1-sided log-rank test. Median TTP with corresponding 95% confidence intervals (CI) will be estimated using Kaplan-Meier (KM) methods. The hazard ratio (Arm A/Arm B) will be estimated by proportional Hazard regression.
    E.5.1.1Timepoint(s) of evaluation of this end point
    interim analysis after 60 events and at end of trial
    E.5.2Secondary end point(s)
    Secondary objectives are to compare the rates of patients, who reach LTx and the frequencies of TACE treatments required between the 2 arms, to assess safety and toxicity, the progression-free survival, overall response rate, complete response (CR) and partial response (PR), disease control rate (DCR) as well as the health-related quality of life (HQoL) and the influence of the treatment on the AFP-level during the trial. Furthermore it is planned to conduct biomarker studies which examine liver biopsies, whole liver specimen after LTx and serum samples for genetic, gene expression and protein alterations. The biomarker findings will be correlated with clinical parameters.
    E.5.2.1Timepoint(s) of evaluation of this end point
    end of trial
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open 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.8.3 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 No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee 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
    provided in the protocol
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    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 years0
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero 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.1.3Elderly (>=65 years) Yes
    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 state192
    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)
    Standard treatment
    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 Decision2008-10-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-10-02
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2013-02-18
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