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    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   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:2008-005942-22
    Sponsor's Protocol Code Number:8669-021
    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:2009-01-19
    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 number2008-005942-22
    A.3Full title of the trial
    A Randomized Discontinuation Phase II Trial of Deforolimus in Non-Small Cell Lung Cancer (NSCLC) Patients with KRAS Mutations
    A.4.1Sponsor's protocol code number8669-021
    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., a subsidiary of Merck & Co. Inc
    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 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 nameDeforolimus
    D.3.2Product code AP23573 or MK-8669
    D.3.4Pharmaceutical form Gastro-resistant tablet
    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.3.8INN - Proposed INNdeforolimus
    D.3.9.1CAS number 572924-54-0
    D.3.9.2Current sponsor codeMK-8669
    D.3.9.3Other descriptive nameAP23573
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboGastro-resistant tablet
    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
    Non-small cell lung cancer, Non-small cell lung cancer metastatic, non-small cell lung cancer NOS, non-small cell lung cancer recurrent, non small cell lung cancer stage III, non-small cell lung cancer stage IIIA, non-small cell lung cancer stage IIIB, non-small cell lung cancer stage IV, Progressions of non-small cell lung cancer.
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10061873
    E.1.2Term Non-small cell lung cancer
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10029514
    E.1.2Term Non-small cell lung cancer NOS
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10029520
    E.1.2Term Non-small cell lung cancer stage IIIA
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10029515
    E.1.2Term Non-small cell lung cancer recurrent
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10029521
    E.1.2Term Non-small cell lung cancer stage IIIB
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10029519
    E.1.2Term Non-small cell lung cancer stage III
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10029522
    E.1.2Term Non-small cell lung cancer stage IV
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10059515
    E.1.2Term Non-small cell lung cancer metastatic
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10066490
    E.1.2Term Progression of non small cell lung cancer
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the efficacy of deforolimus in patients with KRAS mutant NSCLC who have progressed after two prior chemotherapy regimens compared to placebo by progression free survival analysis of randomized patients who have stable disease after an 8-week lead-in treatment with deforolimus.
    E.2.2Secondary objectives of the trial
    In patients with KRAS mutant NSCLC who receive deforolimus after failing two prior chemotherapy regimens, to:
    • Evaluate the safety profile of deforolimus.
    • Evaluate the best overall response rate.
    • Evaluate the overall duration of progression-free survival.
    • Estimate overall survival.
    • Estimate whether continuing therapy with deforolimus improves survival in patients who have experienced stable disease after 8 weeks of therapy with deforolimus.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Patient has histologically confirmed stage IIIB/IV non-small cell lung cancer.
    2.Patient has a documented mutation of the KRAS gene in tumor tissue.
    a.Patients with a known KRAS mutation must have documentation in the source documents, and are strongly encouraged to submit archival tissue material for central confirmation of mutation status.
    b.Patients without a previously documented mutation in the KRAS gene must submit a paraffin block or unstained slides for mutation testing and only those patients who test positive for a KRAS mutation will be eligible (see Study Operations Manual).
    3.Patient has measurable disease by protocol-specific RECIST criteria (see the IIOM).
    4.Patient has evidence of disease progression following 2 prior chemotherapy regimens, one of which was a platinum doublet. No more than 2 prior chemotherapy regimens for treatment of locally advanced or metastatic disease are allowed. Adjuvant (or neoadjuvant) chemotherapy given less than one year before disease recurrence is considered a prior chemotherapy regimen, but one additional prior cytotoxic chemotherapy regimen is allowed if it was given as adjuvant or neoadjuvant therapy more than one year before recurrence or progression to advanced disease.
    a.A prior chemotherapy regimen is defined as a drug regimen used for treatment of lung cancer that contains at least one conventional cytotoxic chemotherapy agent.
    b.Prior kinase inhibitor therapy and prior monoclonal antibody therapy are allowed, alone or in combination with chemotherapy. There is no limit on prior non-cytotoxic agents or regimens.
    5.A minimum of 4 weeks has elapsed between prior chemotherapy and day 1 of study treatment. A minimum of 14 days has elapsed since prior kinase inhibitor therapy or radiotherapy, and a minimum of 6 weeks has elapsed since prior monoclonal antibody therapy (e.g. cetuximab or bevacizumab).
    6.Patient has performance status ≤2 on ECOG Performance Scale (Appendix, 6.1).
    7.Patient voluntarily agreed to participate by giving written informed consent.
    8.Patient is ≥18 years of age on day of signing informed consent.
    9.Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to start of therapy and must use an approved contraceptive method for the entire duration of the study, from the time of study enrollment until 30 days after the last dose of study drug.
    a.Approved contraceptive methods include hormonal contraception, intra-uterine device, diaphragm with spermicide, cervical cap with spermicide, or female condom with spermicide (spermicides alone are not an acceptable method of contraception.)
    b.WOCBP are defined as women who are not surgically sterile or who are not post-menopausal. Post-menopausal women who have been amenorrheic for less than one year are considered to be WOCBP unless they have a documented FSH value in the post-menopausal range.
    10.Male partners of WOCBP agree to use approved methods of contraception for the entire duration of the study.
    11.Patient must be available for periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study.
    E.4Principal exclusion criteria
    1.Patient is known to have active brain metastases. Patients with previously treated brain metastases that are stable for > 3 months are eligible if a current brain MRI (within 28 days of day 1 of study treatment) shows no edema or evidence of progression compared to a prior study at least 3 months ago.
    2.Patient is currently participating or has participated in a study with an investigational compound in or device within 30 days or 5 half lives of the investigational compound (which ever is greater) of initial dosing with study drug.
    3.Patient has previously received rapamycin or rapamycin analogs, including deforolimus, everolimus, or temsirolimus.
    4.Patient is receiving corticosteroids administered at doses greater than those used for normal replacement therapy.
    5.Patient has a history of prior malignancy except for basal cell carcinoma of the skin, carcinoma in situ of the cervix; or any patient who has undergone potentially curative therapy for malignancy with no evidence of that disease for five years or who is deemed at low risk for recurrence by his treating physician.
    6.Patient has known severe hypersensitivity to macrolide antibiotics (ie: clarithomycin, erythromycin, or azythromycin).
    7.Patient has NYHA Class III or IV congestive heart failure or any other significant history of cardiac disease including: myocardial infarction within the last 6 months; ventricular arrhythmia or acute congestive heart failure within the last 3 months; uncontrolled angina or uncontrolled hypertension.
    8.Patient is known to be HIV positive or has a known history of Hepatitis B or C.
    9.Patient has a psychiatric disorder that would interfere with cooperation with the requirements of the trial, is a regular user of illicit drugs (including "recreational use"), or has a recent history (within the last year) of drug or alcohol dependence.
    10.Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study.
    11.Patient has an active infection requiring prescribed intervention.
    12.Patient has a requirement for concurrent treatment with medications that are strong inducers or inhibitors of cytochrome P450 (CYP3A) (see Appendix 6.2). Patients should be off these medications for at least 2 weeks prior to the first dose of deforolimus. Concomitant medications that are metabolized by CYP3A are allowed (e.g., simvastatin or atorvastatin).
    13.Patient has newly diagnosed (within 3 months before enrollment) or poorly controlled Type 1 or 2 diabetes. Poorly controlled diabetes is defined as a fasting glucose >160 mg/dL during screening or being known to have a HbA1C > 8%.
    14.Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study or interfere with the patient's participation for the full duration of the study, or it is not in the best interest of the patient to participate.
    E.5 End points
    E.5.1Primary end point(s)
    Primary Efficacy endpoint:
    Progression-free Survival (PFS) in the randomized population: is defined, in the randomized population, as the time from randomization to progressive disease or death, whichever is earlier. Patients without an event at the time of analysis will be censored at the date of the last tumor assessment.

    Secondary endpoints:
    Overall survival (OS) in the randomized population: is defined, in the randomized population, as the time from randomization to death due to any cause. Patients without documented death at the time of analysis will be censored at the date last known to be alive.
    Overall response rate (ORR) in the FAS population: is defined, in the FAS population, as the proportion of patients whose best response is PR or CR at Week 8.
    Progression Free Survival (PFS) in the FAS population: is defined, in the FAS population, as the time from entry to the study to progressive disease or death, whichever is earlier. Patients without an event at the time of analysis will be censored at the date of the last tumor assessment.
    Overall survival (OS) in the FAS population: is defined, in the FAS population, as the time from entry to the study to death due to any cause. Patients without documented death at the time of analysis will be censored at the date last known to be alive.

    Exploratory endpoint: EQ-5D, a validated instrument for the assessment of overall quality of life (QoL): the questionnaire consists of 5 questions, pertaining to a specific dimension of quality of life: (1) mobility, (2) self-care, (3) usual activities, (4) pain/discomfort and (5) anxiety/depression. Additionally, a sixth question, called the Health State Thermometer, measures a patient's current health state.

    Safety Endpoints: Safety and tolerability will be assessed by a clinical review of all relevant adverse experiences and monitoring variables related to laboratory measurements, ECG, ECOG performance status, physical examinations, and vital signs.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised No
    E.8.1.2Open No
    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 Yes
    E.8.1.7.1Other trial design description
    Randomized Discontinuation Trial
    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 concerned2
    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 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 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
    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 months10
    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 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 Yes
    F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2009-01-19. Yes
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 150
    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 Decision2009-03-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-04-23
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2012-08-29
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