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    The EU Clinical Trials Register currently displays   38870   clinical trials with a EudraCT protocol, of which   6391   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2013-002258-60
    Sponsor's Protocol Code Number:UMCN-ONCO-201302
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2013-08-15
    Trial 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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2013-002258-60
    A.3Full title of the trial
    prediction of everolimus-induced interstitial lung disease in breast cancer patients; maximizing efficacy by reducing toxicity
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    prediction of lung problems as a side effect of treatment with everolimus for patients with breast cancer
    A.3.2Name or abbreviated title of the trial where available
    PREVENT
    A.4.1Sponsor's protocol code numberUMCN-ONCO-201302
    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 SponsorRadboud University Nijmegen Medical Centre
    B.1.3.4CountryNetherlands
    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 supportRadboud University Nijmegen Medical Centre
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationRadboud University Nijmegen Medical Centre
    B.5.2Functional name of contact pointResearch verpleegkundigen oncologie
    B.5.3 Address:
    B.5.3.1Street AddressGeert Grooteplein 10
    B.5.3.2Town/ cityNijmegen
    B.5.3.4CountryNetherlands
    B.5.4Telephone number0031243618800
    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 Afinitor
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Ltd.
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    breast cancer
    E.1.1.1Medical condition in easily understood language
    breast cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10072737
    E.1.2Term Advanced breast cancer
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Analyze the value of pneumoproteins, immunological parameters, everolimus exposure, pulmonary function tests, distinct radiological patterns, baseline patient characteristics and the development of skin toxicity or mucositis for the prediction of the development and severity of everolimus-induced interstitial lung disease.
    E.2.2Secondary objectives of the trial
    Secondary objectives:
    - Determine whether a decline in pulmonary function test or the occurrence of new radiological pulmonary abnormalities is preceded by an increase in the level of pneumoproteins
    - Investigate the pathophysiology of everolimus-induced ILD, skin toxicity and oral mucositis
    - Describe the outcomes of a standardized treatment strategy for everolimus-induced ILD
    - Correlate the development and grade of everolimus-induced ILD, skin toxicity and oral mucositis with everolimus exposure (AUC) and outcome (PFS)
    - Determine the type and frequency of lung parenchymal changes and its discriminative power from other (not drug-related) lung changes
    - Determine the impact of radiological interreader variability on patient management
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
    - Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
    - Postmenopausal women. Postmenopausal status is defined either by:
    o Age ≥ 55 years and one year or more of amenorrhea
    o Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/ml
    o Surgical menopause with bilateral oophorectomy
    - Radiological or clinical evidence of recurrence or progression on last systemic therapy prior to enrollment.
    - Progression following a non-steroidal aromatase inhibitor
    - Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x ULN
    - Adequate renal function: calculated creatinine clearance (as estimated by GFR using the MDRD formula) is MDRD ≥ 30ml/min/1.73m2
    - Performance status ECOG 0 - 2 (Karnofsky index: 60 - 100)
    - Patient is willing and able to sign the Informed Consent Form prior to screening evaluations
    E.4Principal exclusion criteria
    - HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
    - Previous treatment with exemestane or mTOR inhibitors. Except for the treatment with exemestane in the adjuvant setting.
    - Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
    - Patients with a known history of HIV seropositivity.
    - Any severe and / or uncontrolled medical conditions such as:
    o Unstable angina pectoris, serious uncontrolled cardiac arrhythmia
    o Patients with severe hepatic impairment (Child-Pugh A/B/C)
    o Uncontrolled diabetes mellitus
    o Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
    - Patients who test positive for hepatitis B or C (Patients who test negative for HBV-DNA, HBsAg, and HBcAb but positive for HBsAb with prior history of vaccination against Hepatitis B will be eligible). Only patients at higher risk for hepatitis B or C will be tested.
    - Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days prior to enrollment
    - History of non-compliance to medical regimens
    - Patients unwilling to or unable to comply with the protocol
    E.5 End points
    E.5.1Primary end point(s)
    Find the correlation between:
    - baseline patient characteristics (smoking, preexistent lung disease)
    - pneumoproteins; KL-6, surfactant protein A, surfactant protein D, CC16, CCL18, YKL-40, LDH and CA 15.3 (absolute number and difference from baseline)
    - immunologic parameters (i.e. T-cell activation status and cytokine profile, DC subtyping, immune checkpoint proteins)
    - everolimus exposure (AUC on day 14 and mini-AUC at moment of toxicity)
    - pulmonary function tests: spirometry including FVC and DLCO adjusted for hemoglobin (absolute number and difference from baseline)
    - four distinct radiological patterns of 1.0mm CT slices of the lungs (as described in paragraph 6.2.7, page 30)
    - the development and grade of everolimus-induced skin toxicity and oral mucositis
    and the development and grade of everolimus-induced ILD, using univariate and multivariate analysis.
    E.5.1.1Timepoint(s) of evaluation of this end point
    within six months
    E.5.2Secondary end point(s)
    - Analyze the temporal relationship between a decrease in pulmonary function or the occurrence of new radiological pulmonary abnormalities and an increase in the level of pneumoproteins
    - Investigate which immunological changes (cytokines, T-cells, dendritic cells) are observed in peripheral blood, skin biopsies and bronchoalveolar lavage of patients with everolimus-induced toxicity
    - Assess the duration and severity of ILD when patients are treated according to a standardized diagnostic and treatment strategy
    - Define the correlation between everolimus induced ILD on the one hand and everolimus exposure (as per AUC0-24h) on day 14) and outcome (as per PFS) on the other hand
    - Determine the type and frequency of lung parenchymal changes and its discriminative power from other (not drug-related) lung changes
    - Describe the quantity and quality of differences in judgment of HRCT images between a local and a central radiologist
    E.5.2.1Timepoint(s) of evaluation of this end point
    within six months
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy No
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled No
    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
    observational
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    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 concerned7
    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 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
    LVLS
    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
    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.1.2.1Number of subjects for this age range: 75
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 25
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    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 state100
    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)
    none
    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 Decision2013-08-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-08-30
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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