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    The EU Clinical Trials Register currently displays   44173   clinical trials with a EudraCT protocol, of which   7329   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:2005-000731-26
    Sponsor's Protocol Code Number:NEMA-0027-017
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-06-28
    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 ConcernedUK - MHRA
    A.2EudraCT number2005-000731-26
    A.3Full title of the trial
    Nemorubicin hydrochloride (PNU-152243A) administered via intrahepatic artery in combination with cisplatin in adult patients with unresectable hepatocellular carcinoma: Phase II study preceded by dose-escalation.
    A.4.1Sponsor's protocol code numberNEMA-0027-017
    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 SponsorNerviano Medical Sciences S.r.l.
    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 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.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/05/300
    D.3 Description of the IMP
    D.3.1Product nameNemorubicin hydrochloride, 500µg vial
    D.3.2Product code PNU-152243A
    D.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntraarterial use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNemorubicin
    D.3.9.1CAS number 108943-08-4
    D.3.9.3Other descriptive nameMethoxymorpholin Doxorubicin hydrochloride
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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 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 Cisplatino Mayne
    D.2.1.1.2Name of the Marketing Authorisation holder Hospira Italia S.r.l.
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameCisplatin, 1mg/ml (50ml vial)
    D.3.4Pharmaceutical form Sterile concentrate*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntraarterial use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCisplatin
    D.3.9.1CAS number [15663-27-1]
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) 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 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
    Unresectable hepatocellular carcinoma (HCC)
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 13.1
    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 Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the trial is the evaluation of the antitumor efficacy of the combination nemorubicin hydrochloride (HCl) + cisplatin in adult patients with unresectable HCC. The evaluation of the antitumor efficacy will be in terms of response rate (RR, ie the proportion of patients with confirmed objective tumor response [CR or PR] or tumor downstaging allowing tumor lesion ablation by surgery or other ablative techniques relative to the number of evaluable patients). This objective will be pursued upon: identification during the dose-escalation portion of the trial in the targeted populations of the maximum tolerated dose (MTD), dose limiting toxicities (DLT) and the recommended dose of nemorubicin HCl + cisplatin, and characterization of the qualitative/quantitative profile of toxicity.
    E.2.2Secondary objectives of the trial
    - Evaluation of tumor response characteristics (including duration of response, time to progression [TTP], and changes in alpha-fetoprotein [AFP] tumor marker levels). Since systemic exposure with IHA therapy is lower than by systemic administration, complementary exploratory investigation of tumor response characteristics in the liver will be performed.
    - Evaluation of overall survival.
    - Evaluation of safety of repeated administrations of the combo nemorubicin + cisplatin.
    - Evaluation of the pharmacokinetic profile of nemorubicin and cisplatin, when the two drugs are given in combination.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Presence of unresectable, microscopically confirmed HCC, not amenable to any ablation, either newly diagnosed or relapsing after prior surgery, or other prior ablative techniques, or other prior anticancer therapy for HCC, provided that the lesion(s) present at study entry are vascularized through hepatic artery. If biopsy is contraindicated, computerized tomography (CT) or magnetic resonance imaging (MRI) evidence of hepatic tumor and an AFP level of ≥400 ng/mL will be accepted as evidence of HCC.
    2. Intermediate risk population Advanced risk population
    Tumor staging CLIP 0-1 Tumor staging CLIP 2
    bilirubin ≤1.5 x UNL bilirubin ≤2.5 mg/dL
    no portal vein thrombosis portal vein thrombosis admitted
    Child A or B Child A or B
    3. Prior systemic or locoregional anticancer therapy for HCC is allowed, provided that a minimum of 6 weeks have elapsed between the end of prior therapy for HCC and the entry into the study.
    4. At least one bidimensionally measurable disease that is ≥2 cm in at least 1 diameter with conventional CT scan or MRI or ≥1 cm in at least 1 diameter with spiral CT scan. (For Phase II only)

    5. Resolution of all acute toxic effects of any prior surgical procedure or other prior therapy for HCC to NCI CTC Grade ≤1
    6. Age ≥18 yrs of age and ≤75 yrs of age.
    7. Intermediate risk population: ECOG performance status of 0 or 1.
    Advanced risk population: ECOG performance status of 1 or 2.
    8. Life expectancy of at least 12 weeks.
    9. Laboratory data at study entry as specified
    Absolute neutrophil count (ANC) ≥ 1,500/mm3 (≤ CTC Grade 1)
    Platelets ≥ 75,000/mm3 (≤ CTC Grade 1)
    Hemoglobin ≥ 10.0 g/dL (≤ CTC Grade 1)
    Creatinine ≤ 1.5 x UNL (≤CTC Grade 1)
    Creatinine clearance > 30 mL/min (Cockcroft formula)
    ALT ≤ 2.5 x ULN (≤ CTC Grade 1)
    AST≤ 2.5 x ULN (≤ CTC Grade 1)
    Alkaline phosphatase ≤ 2.5 x ULN (≤ CTC Grade 1)
    Partial thromboplastin time (APTT) ≤1.5 x ULN (≤ CTC grade 1)
    Prothrombine time (PT) ≤1.5 x UNL (≤ CTC grade 1)
    INR > 1-1.5 xUNL (≤ CTC grade 1)
    Left ventricular ejection fraction (LVEF) - Within normal institutional limits
    Pregnancy test for females of childbearing potential - Negative
    within 7 days of starting treatment

    10. Signed and dated informed consent document indicating that the patient (or legally acceptable representative or witness in case of oral consent) has been informed of all pertinent aspects of the trial and he/she is able to comply with the treatment plan, scheduled clinic visits, laboratory tests, oncologic tests, and other study procedures.
    E.4Principal exclusion criteria
    1. Histologic classification of HCC, fibrolamellar variant.
    2. Current enrollment in another clinical trial.
    3. Patients with vascular invasion (in particular, with complete obstruction of the portal vein) as documented by imaging techniques (for intermediate risk population only).
    4. Patients with extra-hepatic spread.
    5. Administration of any prior systemic or intra-arterial anticancer therapy for HCC containing platinum derivatives.
    6. Prior liver transplantation.
    7. Administration of any prior radiotherapy to treat the tumor lesion(s) present at study entry.
    8. Extrahepatic metastatic disease including known brain or leptomeningeal disease (baseline CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system metastases).
    9. No longer applicable.
    10. Presence of clinically detectable ascites or pleural effusions
    11. Recent bleeding (within prior 6 months) from esophageal varices.
    12. Symptomatic ulceration of the gastric or duodenal mucosa ≤ 30 days prior to enrollment.
    13. Any known bleeding diathesis.
    14. Failure of angiography due to anatomical or technical reasons (see Section 9.2)
    15. Currently active second malignancy, other than non-melanoma skin cancers and /or cone-biopsied in situ carcinoma of the cervix uteri. Patients with other malignancies must have been disease free for ≥2 years.
    16. Any of the following in the past within the last year: myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other significant thromboembolic event.
    17. Any prior history of symptomatic congestive heart failure.
    18. Irreversible cardiac arrhythmias requiring permanent medication or uncontrolled arterial hypertension (arterial pressure ≥200/110 mmHg).
    19. Active infection other than chronic active hepatitis. Patients with known human immunodeficiency virus (HIV) positivity or acquired-immunodeficiency-syndrome (AIDS)-related illness are not eligible.
    20. Pregnancy or breast-feeding. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of chemotherapy. Male patients must be surgically sterile or must agree to use effective contraception during the period of chemotherapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
    21. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
    22. Allergy to the contrast agent
    E.5 End points
    E.5.1Primary end point(s)
    Dose-escalation portion:
    - First cycle DLTs to be used for MTD identification.
    - Laboratory and clinical safety parameters (including cardiac function monitoring).
    - Adverse events emerging during the trial.

    Phase II portion:
    Overall Confirmed Objective Tumor Response: defined as a best confirmed response of CR or PR, or a tumor downstaging allowing for tumor lesion surgery or ablation. Objective tumor responses will be determined according to modified World Health Organization (WHO) criteria. As per WHO criteria, confirmed responses are those that are confirmed to persist on a follow-up instrumental tumor assessment 3/4 weeks after the initial objective documentation of response. In addition, surgical intervention performed in patients who are in CR/PR, before their tumor responses can be instrumentally re-assessed, will be considered as confirmation of tumor 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) 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 No
    E.8.1.1Randomised No
    E.8.1.2Open Information not present in EudraCT
    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 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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    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 Information not present in EudraCT
    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
    See Protocol Section 9.2.4
    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.1.1.1In 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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Signed Inform Consent from a Legal Representative required.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 125
    F.4.2.2In the whole clinical trial 125
    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 Decision2005-08-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2006-03-28
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2012-04-19
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