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    The EU Clinical Trials Register currently displays   43839   clinical trials with a EudraCT protocol, of which   7280   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:2008-000912-34
    Sponsor's Protocol Code Number:PR003-CLN-pro001
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2008-04-11
    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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2008-000912-34
    A.3Full title of the trial
    A PHASE 2 STUDY OF THE ANTI-TUMOUR ACTIVITY AND SAFETY OF PROLARIX™ IN HEPATOCELLULAR CARCINOMA (HCC)
    A.4.1Sponsor's protocol code numberPR003-CLN-pro001
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorProtherics Development Medicines Ltd
    B.1.3.4CountryUnited Kingdom
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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.2.1.1.1Trade name Prolarix
    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 nameProlarix
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNTretazicar
    D.3.9.1CAS number 21919-05
    D.3.9.2Current sponsor codeTretazicar
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number19.1
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCarictotamide
    D.3.9.1CAS number 64881-21-6
    D.3.9.2Current sponsor codeCaricotamide
    D.3.9.3Other descriptive name3-(Aminocarbonyl)-1(4H)-pyridineacetamide
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 Information not present in EudraCT
    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 (HCC)
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10019828
    E.1.2Term Hepatocellular carcinoma non-resectable
    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 the overall response rate [ie, proportion of subjects with complete response (CR) and partial response (PR)] to treatment with Prolarix at the MTD determined in a previous Phase 1 study (26.6 mg/m2 tretazicar co-administered with 200 mg/m2 caricotamide).
    E.2.2Secondary objectives of the trial
    Secondary Objectives:

    To evaluate the disease control rate defined as the proportion of subjects with either CR or PR or stable disease (SD) at tumour assessment performed approximately 12 weeks or more after first treatment with Prolarix.

    To evaluate time to tumour progression (TTP).

    To evaluate indications of anti-tumour activity as supported by post-treatment changes in the amount of contrast-enhancing and non-contrast-enhancing tumour and by changes in alpha fetoprotein.

    To evaluate the toxicity profile of Prolarix in subjects with HCC.

    To evaluate the pharmacokinetic profiles of tretazicar and caricotamide in subjects with HCC.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects must meet all of the following criteria to be eligible for enrolment into the study:

    1) Subject must be ≥18 years of age.

    2) Subject must have a histologic or cytologic diagnosis of HCC and be considered unsuitable for resection or other potentially curative options (eg, liver transplant, curative radiofrequency ablation). [Note: Subjects who have not yet had a tissue diagnosis may enter the Screening phase of the study if a) their clinical presentation is considered highly suggestive of HCC by the principal investigator and b) a tissue diagnosis is considered necessary for their management (subjects whom a tissue diagnosis is not considered essential for their management should not be enrolled on this study). A tissue diagnosis must be obtained prior to the entry of any subject into the treatment phase of the study. Subjects whom the principal investigator deems core biopsy to be indicated (as opposed to fine needle aspiration), will be requested to provide informed consent for a second pass biopsy (ie, in addition to the first pass biopsy for tissue diagnosis) for quantification of enzyme DT- diaphorase (NQO2) activity. The second pass biopsy is optional and subjects refusing a second pass biopsy may be enrolled in the study and will be treated identically to those accepting the second pass biopsy].

    3) Subject must have a measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) on CT scan in at least one site which has not received radiation or any other local therapy [eg, transcatheter arterial chemoembolisation (TACE), radiofrequency ablation, local injection]. (Note: Subjects who have received local therapies will be allowed to participate provided that they have a target lesion which has not been subjected to local therapy. Subjects who have received TACE must have a target lesion outside of the vascular territory subjected to chemoembolisation).

    4) Subject has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.

    5) Subject has had no other active malignancy within the past three years [other than non melanomatous skin cancer or carcinoma in situ (CIS) of the breast, bladder or uterine cervix. Subjects with Ta (non-invasive papillary carcinoma) or Tis (sessile carcinoma in situ) bladder cancer are allowed].

    6) Subject has a minimum life expectancy of at least three months as determined by the investigator.

    7) Subject has adequate bone marrow function (ie, haemoglobin ≥9 g/dL, granulocytes ≥1500/mm3, platelets ≥75,000/mm3).

    8) Prothrombin time (PT)-international normalised ratio (INR) ≤2.3 or PT ≤ equal to 6 seconds above control. (Note: Subjects who are being therapeutically anticoagulated with an agent such as warfarin or heparin will be allowed to participate provided that their INR is between 2.0 and 3.0).

    9) Subject has adequate renal function (ie, serum creatinine clearance is normal or calculated creatinine clearance is ≥60 mL/min).

    10) Subject has adequate hepatic function (ie, bilirubin ≤2x upper limit of normal (ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤5xULN). (Also see exclusion for Child-Pugh class C below).

    11) Male subjects and females of childbearing potential must agree to use an adequate method of contraception from the time of initiation of treatment through study participation and for 3 months after release from the study.

    12) Subject is able to give informed consent.
    E.4Principal exclusion criteria
    Subjects meeting any of the following exclusion criteria will not be eligible for enrolment:

    1) Any prior or current systemic pharmacotherapy for HCC (cytotoxic, targeted or biologic). (Note: TACE is not considered to be systemic pharmacotherapy for the purpose of this study.)

    2) Subject has an absolute contraindication to receiving CT contrast media. (Note: Subjects with a history of minor contrast reactions may be pre-medicated prior to contrast administration in accordance with local or institutional practice).

    3) Subject has Child-Pugh Class C hepatic impairment.

    4) Subject has received an investigational drug within 30 days of enrolment in the study.

    5) Females of childbearing potential unless using adequate contraception.

    6) Pregnant or lactating females.

    7) Major variceal bleeding in the last 30 days.

    8) Subjects with a known history of human immunodeficiency virus (HIV) infection
    E.5 End points
    E.5.1Primary end point(s)
    Overall tumour response will be based on the best tumour response in all subjects. Tumour responses for targeted and non-targeted tumours are defined using modified RECIST criteria with the modification that confirmatory CT is not required to define tumour response

    Evaluation of target lesions

    1) Complete Response (CR): Disappearance of all target lesions

    2) Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

    3) Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

    4) Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions

    Evaluation of non-target lesions

    1) Complete Response (CR): Disappearance of all non-target lesions and normalisation of tumour marker level.

    2) Incomplete Response/ Stable Disease (SD): Persistence of one or more non-target lesion(s) or/and maintenance of tumour marker level above the normal limits

    3) Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

    The primary efficacy variable is overall best response rate (proportion of subjects with CR or PR as defined by modified RECIST). Other secondary variables of clinical interest include disease control rate, TTP, indications of anti-tumour effect as evidenced by post treatment changes in the amount of contrast-enhancing and non-contrast-enhancing tumour and by changes in alpha-fetoprotein, duration of best response, and time to best response.
    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 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) Information not present in EudraCT
    E.7.1.1First administration to humans Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Information not present in EudraCT
    E.7.4Therapeutic use (Phase IV) Information not present in EudraCT
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Information not present in EudraCT
    E.8.1.2Open No
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States No
    E.8.5.1Number of sites anticipated in the EEA1
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    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
    End of the trial will be the last patient last visit
    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 months10
    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 months10
    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 Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 5
    F.4.2.2In the whole clinical trial 20
    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 Decision2008-05-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-05-05
    P. End of Trial
    P.End of Trial StatusCompleted
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