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    Summary
    EudraCT Number:2014-000428-12
    Sponsor's Protocol Code Number:CLEE011X2201
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2021-05-27
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2014-000428-12
    A.3Full title of the trial
    A randomized, blinded, placebo-controlled, phase II trial of LEE011 in patients with relapsed, refractory, incurable teratoma with recent progression
    Studio randomizzato, in cieco, controllato versus placebo, di Fase II con LEE011 in pazienti con teratoma recidivante, refrattario, incurabile, in progressione recente
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study for patients with relapsed, refractory,incurable teratoma with recent progression. The study is randomized (the patient may receive the investigational drug or placebo) and it is blinded (the patient and the study doctor will not know what drug the patient receives)
    Studio dell¿efficacia e della sicurezza d¿impiego di LEE011, in pazienti con teratoma recidivante, refrattario, incurabile, in progressione recente
    A.3.2Name or abbreviated title of the trial where available
    NA
    NA
    A.4.1Sponsor's protocol code numberCLEE011X2201
    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 SponsorNOVARTIS FARMA S.P.A.
    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 supportNovartis Pharma Services AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Farma S.p.A.
    B.5.2Functional name of contact pointDrug Regulatory Affairs
    B.5.3 Address:
    B.5.3.1Street AddressLargo Umberto Boccioni,1
    B.5.3.2Town/ cityOriggio
    B.5.3.3Post code21040
    B.5.3.4CountryItaly
    B.5.4Telephone number02-96541
    B.5.5Fax number02-9659066
    B.5.6E-mailinfo.studiclinici@novartis.com
    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 nameNA
    D.3.2Product code LEE011
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    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 1374639-75-4
    D.3.9.2Current sponsor codeLEE011
    D.3.9.4EV Substance CodeSUB31644
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule, hard
    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
    relapsed, refractory, incurable teratoma
    teratoma recidivante, refrattario, incurabile
    E.1.1.1Medical condition in easily understood language
    relapsed, refractory, incurable teratoma
    teratoma recidivante, refrattario, incurabile
    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 PT
    E.1.2Classification code 10043276
    E.1.2Term Teratoma
    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 assess the efficacy of LEE011 compared to placebo in patients with relapsed/refractory teratoma with recent progression
    Valutare l¿efficacia di LEE011 in confronto a placebo in pazienti con teratoma recidivante, refrattario, in progressione recente.
    E.2.2Secondary objectives of the trial
    1.To assess other measures of efficacy of LEE011 compared with placebo
    2.To assess safety and tolerability of LEE011 compared with placebo
    1.Valutare altre misure di efficacia di LEE011 in confronto a placebo.
    2.Valutare la sicurezza d¿impiego e la tollerabilit¿ di LEE011 in confronto a placebo.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives

    Other types of substudies
    Specify title, date and version of each substudy with relative objectives: Title: Survey complementary option for the evaluation of biological indicators additional
    Objectives: Evaluation of biological indicators
    Version: 01
    Date: 24.10.2014

    Altre tipologie di sottostudi
    specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Titolo: Indagine complementare opzionale per la valutazione degli indicatori biologici aggiuntivi
    Obiettivi: valutazione degli indicatori biologici
    Versione: 01
    Data: 24.10.2014
    E.3Principal inclusion criteria
    1. Diagnosis of teratoma for which no additional standard surgical or medical therapy exists
    2. Patients must have completed at least 1 prior line of chemotherapy for germ cell tumor
    3. Radiographic progression, defined by RECIST v.1.1, after the last cancer treatment and within 12 weeks prior to enrollment, compared with scans within 1 year of enrollment.
    4. Availability of an archival or newly obtained tumor sample (collected at diagnosis or progression) with accompanying pathology report
    5. Measurable or evaluable extra-cranial disease as defined by RECIST v 1.1
    Other protocol-defined inclusion criteria may apply
    1.Pazienti di età = 15 anni al momento del consenso informato.
    2.Diagnosi di teratoma per il quale non esiste alcuna terapia medica o chirurgica standard aggiuntiva.
    3.Disponibilità di un campione di tumore archiviato o prelevato allo scopo (prelevato alla diagnosi o alla progressione) con il referto istologico corrispondente.
    •I pazienti che non hanno a disposizione un campione tumorale possono essere inclusi nello studio dopo discussione tra Novartis e lo sperimentatore.
    4.I pazienti devono aver completato almeno 1 linea precedente di chemioterapia per tumori a cellule germinali.
    5.Progressione radiografica, definita da RECIST v.1.1, dopo l’ultimo trattamento antitumorale ed entro 12 settimane prima dell’arruolamento, confrontata con le scansioni eseguite entro 1 anno dall’arruolamento.
    6.Malattia extra-cranica misurabile o valutabile, definita in base a RECIST v.1.1.
    7.I pazienti devono presentare ECOG performance status di 0-1.
    8.Il consenso informato scritto/l’assenso deve essere ottenuto prima di qualsiasi procedura di screening. Nei pazienti pediatrici il consenso sarà ottenuto dai genitori o dal tutore e sarà necessaria la firma di entrambi i genitori o del tutore. Gli sperimentatori otterranno anche l’assenso dei pazienti in base alle linee-guida nazionali.
    E.4Principal exclusion criteria
    1.Malignant germ cell tumors with mixed histology such as embryonal carcinoma, choriocarcinoma, yolk sac tumor or seminoma
    2. Pathologic evidence of malignant transformation
    3. CNS disease unless radiation therapy and/or surgery has been completed and serial evaluation demonstrates stable disease
    4. Prior treatment with any CDK4/6 inhibitor therapy
    5. Systemic antineoplastic therapy or any experimental therapy within 3 weeks before the first dose of study drug (6 weeks for prior nitrosoureas, bevacizumab, or mitomycin C)
    6. Major surgery = 2 weeks or radiotherapy = 4 weeks prior to planned start of study drug or patient has not recovered from major side effects.
    7. Requirement for treatment with any of the prohibited medications including strong CYP3A inhibitors, strong CYP3A inducers, CYP3A
    substrates with a narrow therapeutic index, and medications with strong risk of QT prolongation.
    Other protocol-defined Exclusion criteria may apply
    1.Malattia del sistema nervoso centrale a meno che non siano stati completati la radioterapia e/o l’intervento chirurgico e le valutazioni seriali mediante TAC (con mezzo di contrasto) o RMN nell’arco di un minimo di 2 mesi dimostrino malattia stabile. I pazienti devono essere asintomatici e non devono avere necessità di trattamento con corticosteroidi sistemici o farmaci antiepilettici.
    2.Tumori a cellule germinali maligni diversi da quello trattato nel presente studio, compresi tumori con elementi di istologia mista come ad esempio il carcinoma embrionale, il coriocarcinoma, il tumore del seno endodermico o il seminoma.
    3. Evidenza patologica di trasformazione maligna.
    4. Neoplasie concomitanti diverse dal teratoma entro 3 anni dalla randomizzazione con l'eccezioni aggiuntive di NSGCT trattato dal quale è emerso il teratoma, carcinoma cutaneo a cellule basali o a cellule squamose adeguatamente trattato, carcinoma della cervice uterina trattato chirurgicamente o carcinomi in situ di qualsiasi tipo trattati chirurgicamente.
    5.Trattamento precedente con una terapia con inibitore di CDK4/6.
    6. Qualsiasi condizione medica concomitante grave e/o non controllata che, secondo l’opinione dello sperimentatore,rappresenti una controindicazione alla partecipazione del paziente allo studio (ad es. pancreatite cronica, epatite in fase attiva,epatite virale o positività HIV nota). Non è richiesto lo screening HIV al basale.
    7. Pazienti che non hanno presentato guarigione a CTCAE < Grado 1 dagli effetti tossici acuti (a eccezione di alopecia) di tutte le chemioterapie, immunoterapie o radioterapie precedenti.
    8. Compromissione della funzionalità gastrointestinale o pazienti con patologie gastrointestinali che possono alterare
    significativamente l’assorbimento dei trattamenti in studio (ad es.colite ulcerosa, nausea non controllata, vomito, diarrea, sindrome da malassorbimento o resezione dell’intestino tenue).
    9. Compromissione della funzionalità cardiaca o cardiopatie clinicamente rilevanti, compresa qualsiasi condizione seguente:
    - Frazione di eiezione del ventricolo sinistro (LVEF) < 45% o inferiore al limite inferiore della norma per l’istituzione,determinata mediante angioscintigrafia (MUGA) o ecocardiogramma.
    -Sindrome del QT lungo congenita o familiarità per morte cardiaca improvvisa inattesa.
    -QT corretto con la formula di Fredericia (QTcF) > 450 msec nei maschi e > 470 ms nelle femmine all’ECG di screening.
    -Cardiopatia clinicamente rilevante, quale scompenso cardiaco che richiede trattamento (NYHA Grado > 2), angina instabile o infarto miocardico entro gli ultimi 3 mesi. Qualsiasi altra
    cardiopatia clinicamente rilevante, quale aritmia instabile,bradicardia a riposo, blocco di branca destra, blocco bifascicolare o qualsiasi cardiopatia che richiede l’impiego di un pacemaker cardiaco < 3 mesi dall’inizio del trattamento in studio.
    - Pazienti in terapia attuale con farmaci con un rischio noto per determinare prolungamento dell’intervallo QT o indurre torsione di punta e che non possono essere sospesi o sostituiti con un farmaco differente.
    10. Terapia concomitante che preclude l’arruolamento:
    -Terapia antitumorale sistemica o qualsiasi terapia
    sperimentale entro 3 settimane prima della somministrazione della prima dose del farmaco in studio (6 settimane per nitrosourea, bevacizumab o mitomicina C somministrati in precedenza).
    -Corticosteroidi sistemici entro 2 settimane prima dell’inizio della somministrazione del trattamento in studio.
    Nota: I corticosteroidi sono consentiti in dosi singole, applicazioni topiche (ad es. per eruzione cutanea), spray per via inalatoria (ad es. per patologie ostruttive delle vie aeree), colliri o
    iniezioni locali (ad es. intra-articolari).
    11. Pazienti sottoposti a intervento chirurgico maggiore entro le ultime 2 settimane prima della somministrazione della prima dose del trattamento in studio (mediastinoscopia, posizionamento di un
    accesso venoso centrale o di un sondino naso-gastrico non sono considerati un intervento chirurgico maggiore).
    12. Pazienti sottoposti a radioterapia < 4 settimane o radioterapia a campo limitato per la terapia palliativa < 2 settimane prima della randomizzazione o pazienti che non hanno presentato risoluzione della tossicità relativa a < CTCAE Grado 1 .
    13. Necessità di trattamento con qualsiasi farmaco non consentito compresi forti inibitori del CYP3A, forti induttori del CYP3A,substrati del CYP3A con un indice terapeutico stretto e farmaci con un rischio elevato di determinare prolungamento del QT
    (Vedi Appendice 4).
    14. Partecipazione a un precedente studio clinico sperimentale entro 30 giorni prima dell’arruolamento o entro 5 emivite del farmaco sperimentale, qualunque sia più lungo.
    15. Qualsiasi paziente con i seguenti valori di laboratorio al di fuori del range:
    -Conta neutrofila assoluta (ANC) < 1,5 x 109/L
    -Piastrine < 100 x 10/L
    -Emoglobina (Hgb) < 9,0 g/dL
    Per ulteriori criteri di inclusione vedere il protocollo
    E.5 End points
    E.5.1Primary end point(s)
    Progression Free Survival (PFS) as per RECIST v1.1 (by local investigator assessment)
    Sopravvivenza libera da progressione (PFS) in base a RECIST v1.1 (mediante valutazione dello sperimentatore localmente)
    E.5.1.1Timepoint(s) of evaluation of this end point
    At 4 months
    A 4 mesi
    E.5.2Secondary end point(s)
    1.Best Overall Response (BOR),Overall response rate (ORR), Duration of Response (DOR), Disease Control Rate (DCR) as per RECIST v1.1, Overall
    Survival (OS) and OS rate; Incidence and severity of adverse events and serious adverse events,changes in laboratory values, and electrocardiograms will be used to
    assess the safety as per CTCAE v.4.03. Dose interruptions and changes will be used to assess the tolerability.
    Miglior risposta complessiva (BOR), tasso di risposta complessiva (ORR),durata della risposta (DOR), tasso di controllo della malattia (DCR), sopravvivenza globale (OS) e tasso di OS.; L'incidenza e la gravit¿ degli eventi avversi e di eventi avversi gravi, cambiamenti nei valori di laboratorio, e elettrocardiogrammi saranno utilizzati per valutare la sicurezza d'impiego secondo CTCAE v.4.03. Per valutare la tollerabilit¿ saranno utilizzate modifiche ed interruzioni nella dose.
    E.5.2.1Timepoint(s) of evaluation of this end point
    At 4 months (BOR, ORR, DOR, DCR) or 12 months (OS, OS rate); Study duration
    A 4 mesi ( BOR,ORR,DOR,DCR) o 12 mesi (OS e tasso di OS); Durata dello studio.
    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 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 Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    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.8.2.4Number of treatment arms in the trial2
    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 EEA12
    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
    United States
    France
    Italy
    Netherlands
    Spain
    United Kingdom
    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
    The study data will be analyzed and a primary clinical study report will be written based on all patients' data at the time when there are
    approx. 23 PFS events for the primary efficacy analysis, or if the study is terminated early. Additional data for patients continuing on study or
    in survival follow-up past the data cutoff date for the primary CSR will be reported in a final CSR once the treatment period, safety follow-up, disease follow-up and survival follow-ups have ended for all patients
    L¿analisi primaria di efficacia sar¿ eseguita quando vi saranno approssimativamente 23 eventi PFS e tutti i pazienti saranno stati seguiti per la PFS per almeno 6 mesi o avranno sospeso prima di questo periodo di tempo per progressione della malattia o decesso, oppure avranno ritirato il proprio consenso al follow-up o saranno stati persi al follow-up oppure se lo studio sar¿ concluso anticipatamente.
    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 Yes
    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) Yes
    F.1.1.6.1Number of subjects for this age range: 15
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 22
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 5
    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 26
    F.4.2.2In the whole clinical trial 42
    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)
    NA
    NA
    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 Decision2015-09-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-03-26
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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