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    The EU Clinical Trials Register currently displays   35479   clinical trials with a EudraCT protocol, of which   5824   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2005-000949-11
    Sponsor's Protocol Code Number: 014-10
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    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 number2005-000949-11
    A.3Full title of the trial
    A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Oral
    Suberoylanilide Hydroxamic Acid (L-001079038) in Patients With Advanced Malignant
    Pleural Mesothelioma Previously Treated With Systemic Chemotherapy
    A.3.2Name or abbreviated title of the trial where available
    Phase III Advanced Mesothelioma Study
    A.4.1Sponsor's protocol code number 014-10
    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 SponsorMerck Sharp & Dohme Corp.
    B.1.3.4CountryUnited States
    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 Information not present in EudraCT
    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 namesuberoylanilide hydroxamic acid (SAHA)
    D.3.2Product code CN-0683/L-001079038
    D.3.4Pharmaceutical form Capsule*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 149647-78-9
    D.3.9.2Current sponsor codeCN-0683/L-00107938
    D.3.9.3Other descriptive nameN-hydroxy-N'-phenyl-octane-1, 8-dioic acid diamide
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    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 Yes
    D.3.11.13.1Other medicinal product typecytotoxic oncology medication
    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 placeboCapsule*
    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
    Mesothelioma
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 13.1
    E.1.2Level PT
    E.1.2Classification code 10027406
    E.1.2Term Mesothelioma
    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
    To compare the overall survival associated with L-001079038 plus best supportive care versus that associated with placebo plus best supportive care for the treatment of patients with advanced malignant pleural mesothelioma who have failed at least one prior chemotherapy that has included pemetrexed in combination with either cisplatin or carboplatin regimen, and to determine the overall safety and toxicity of L-001079038 in this population
    E.2.2Secondary objectives of the trial
    To compare between L-001079038 plus best supportive care versus placebo plus best supportive care for the treatment of patients with advanced malignant mesothelioma who have failed at least one prior chemotherapy that included pemetrexed in combination with either cisplatin or carboplatin regimen with respect to:
    a. Progression-free-survival
    b. Overall ORR;
    c Time-to-progression;
    d. Dyspnea score of lung cancer symptom scale modified for mesothelioma (LCSS-Meso) at Week 12; and
    e. Percent change from baseline in forced vital capacity (FVC) at Week 12.
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    a. Patient must have a histologically and/or cytologically confirmed diagnosis of epithelial, sarcomatoid, or mixed histology malignant pleural mesothelioma and:
    In countries where premetrexed is an approved mesothelioma treatment, the patient's mesothelioma has progressed or relapsed following treatment with at least one prior chemotherapy regimen with premetrexed and either cisplatin or carboplatin. OR In countires where premetrexed is not approved for mesothelioma, the patient's mesothelioma has progressed or relapsed following treatment with at least one prior chemotherapy regimen. OR In the opinion of the investigator, premetrexed is not the preferred therapy for the patient, and the patient's mesothelioma has progressed or relapsed following treatment with at least one prior chemotherapy regimen.

    b. Patient must have received no more then 2 prior systemic therapy regimens.
    c. Patient must have an area of pleural thickness measured by using the modified RECIST that is at least 1.5 cm in diameter on a spiral computerized tomography (CT) scan.
    d. Patient is at least 18 years.
    e. Patient has a karnofsky performance scale status of ≥70
    f. Patient has adequate bone marrow function without current use of colony stimulating factors
    g. Patient has adequate coagulation
    h. Patient has adequate liver function
    i. Patient has adequate kidney function.

    Extension Phase
    Any patient who was previously enrolled on MK-0683 P014 who did not experience progression of malignant pleural mesothelioma while receiving treatment with vorinostat will have the option to enroll in a Treatment Extension Phase of the study. This option will be available if the investigator believes that the patient may benefit from treatment with open label vorinostat to treat their malignant pleural mesothelioma. Investigators will have up to three months from the time that they are notified of the final study results to enroll patients into the Treatment Extension Phase.
    The following patients may enroll in the Treatment Extension Phase
    • patients who are receiving treatment with vorinostat and have not experienced progression of mesothelioma
    • patients who were randomized to the placebo arm and meet the eligibility criteria for the Treatment Extension Phase outlined in Section I. D. 3
    • for those patients assigned to vorinostat who have discontinued study therapy for reasons other than progression of mesothelioma, it is left to the investigator's discretion as to whether the potential benefit outweighs potential risks associated with using vorinostat
    b. Female patient must either be post-menopausal or surgically sterilized or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the Treatment Extension Phase starting with Day 1 of the Treatment Extension Phase and for at least 30 days after the last dose of vorinostat. Male patient must agree to use an adequate method of contraception for the duration of the Treatment Extension Phase.
    Patient has the ability to understand and willingness to sign the Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form.
    For those patients who are not currently receiving vorinostat as the study therapy when they transition to the Treatment Extension Phase, the following inclusion criteria regarding performance status and organ function as determined by laboratory testing must be fulfilled:
    d. Patient has a Karnofsky performance scale status of ≥70 (see Appendix 1).
    e. Patient has adequate bone marrow function without current use of colony stimulating factors:
    • Absolute neutrophil count (ANC) ≥1000 /μL,
    • Platelets ≥100,000 /μL,
    • Hemoglobin ≥9.0 g/dL.
    f. Patient has adequate coagulation:
    • Prothrombin time ≤1.5 x the upper limit of normal (ULN) unless receiving therapeutic anticoagulation.
    g. Patient has adequate liver function:
    • ALT (SGPT) and AST (SGOT) ≤2.5 x ULN; or ≤5 x ULN if enzyme abnormalities are due to liver metastases,
    • Bilirubin ≤1.5 x ULN.
    h. Patient has adequate renal function:
    • Creatinine ≤1.5 x ULN.

    E.4Principal exclusion criteria
    a. Patient had prior treatment with an HDAC inhibitor (e.g., Depsipeptide, MS 275, LAQ-824, PXD-101, and valproic acid). Patients who have received such agents for other indications (eg epilepsy) may enroll after a 30-day wash-out.
    b. Patient has an active infection or had received intravenous antibiotic, antiviral, or antifungal medications within 2 weeks prior to the start of study drug.
    c. Patients with a "currently active" second malignancy other than non-melanoma skin cancers and carcinoma in situ of the cervix are not eligible. Patients are not considered to have a "currently active" second malignancy if they have completed therapy for the second malignancy and are disease free from prior malignancies for >5 years.
    d. Patient has uncontrolled brain metastases, e.g., previously treated brain metastases that is not stable in the last 6 weeks.
    e. Patient has a known human immunodeficiency virus (HIV) infection or HIV-related malignancy.
    f. Patient is pregnant or breastfeeding.
    g. Patient has a known allergy to any component of the study drug.
    H. Patient has a history of gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drug.
    i. Patient has any poorly controlled intercurrent illness or circumstances that could limit compliance with the study.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint of this study is overall survival. Survival is generally considered to be the best measurement of an oncology drug’s effectiveness.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Information not present in EudraCT
    E.6.2Prophylaxis Information not present in EudraCT
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Information not present in EudraCT
    E.6.8Bioequivalence Information not present in EudraCT
    E.6.9Dose response Information not present in EudraCT
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic Yes
    E.6.13Others Information not present in EudraCT
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    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) Information not present in EudraCT
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) Information not present in EudraCT
    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 Information not present in EudraCT
    E.8.1.4Double blind Yes
    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) No
    E.8.2.2Placebo Yes
    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.8.5The trial involves multiple Member States Yes
    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 Information not present in EudraCT
    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 first interim analysis will occur after 50 patients have had 18 weeks of follow-up. The second interim analysis will occur after 220 patients have had 18 weeks of follow-up. The third interim analysis will occur after approximately 270 events have occurred.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months26
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months26
    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 Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    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 state59
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 660
    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 Decision2005-07-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-07-28
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2011-11-21
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