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    Summary
    EudraCT Number:2014-000293-20
    Sponsor's Protocol Code Number:INCB18424-362
    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:2014-06-23
    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 number2014-000293-20
    A.3Full title of the trial
    INCB 18424-362
    A Randomized, Double-Blind, Phase 3 Study of the JAK1/2 Inhibitor, Ruxolitinib or Placebo in Combination With Capecitabine in Subjects With Advanced or Metastatic Adenocarcinoma of the Pancreas Who
    Have Failed or Are Intolerant to First-Line Chemotherapy
    (The JANUS 1 Study)
    INCB 18424-362 Studio di Fase 3, randomizzato, in doppio cieco dell'inibitore di JAK1/2, ruxolitinib, o placebo in associazione a capecitabina in soggetti con adenocarcinoma del pancreas in stadio avanzato o metastatico che non hanno risposto o che sono intolleranti alla chemioterapia di prima linea (studio JANUS 1)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A randomized, double-blind, study of ruxolitinib or placebo in combination with capecitabine as second line treatent for Subjects With Pancreatic cancer (The JANUS 1 Study)
    Studio randomizzato, in doppio cieco di ruxolitinib o placebo in associazione a capecitabina come trattamento di seconda linea in pazienti con tumore al pancreas (studio JANUS 1)
    A.3.2Name or abbreviated title of the trial where available
    The JANUS 1 Study
    Studio JANUS 1
    A.4.1Sponsor's protocol code numberINCB18424-362
    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 SponsorIncyte Corporation
    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 supportIncyte Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIncyte Corporation
    B.5.2Functional name of contact pointClinical Trials Information
    B.5.3 Address:
    B.5.3.1Street AddressExperimental Station, Rt 141 & Henry Clay Road
    B.5.3.2Town/ cityWilmington
    B.5.3.3Post codeDE 19880
    B.5.3.4CountryUnited States
    B.5.5Fax number13024252734
    B.5.6E-mailRegAffairs@incyte.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 Yes
    D.2.1.1.1Trade name Jakafi
    D.2.1.1.2Name of the Marketing Authorisation holderIncyte Corporation
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 nameruxolitinib
    D.3.2Product code INCB018424
    D.3.4Pharmaceutical form Tablet
    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.3.8INN - Proposed INNruxolitinib
    D.3.9.1CAS number 941678-49-5
    D.3.9.2Current sponsor codeINCB018424
    D.3.9.3Other descriptive name(R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3- cyclopentylpropanenitrile phosphate
    D.3.9.4EV Substance CodeSUB31642
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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.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 Capecitabine Actavis
    D.2.1.1.2Name of the Marketing Authorisation holderActavis Group PTC ehf
    D.2.1.2Country which granted the Marketing AuthorisationIceland
    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 nameCapecitabine
    D.3.2Product code N/A
    D.3.4Pharmaceutical form Film-coated tablet
    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.3.8INN - Proposed INNCapecitabine
    D.3.9.1CAS number 1158798-73-3
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameN(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine
    D.3.9.4EV Substance CodeSUB12474MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCapecitabine
    D.3.9.1CAS number 1158798-73-3
    D.3.9.2Current sponsor codeN/A
    D.3.9.3Other descriptive nameN(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine
    D.3.9.4EV Substance CodeSUB12474MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    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
    Male or female, 18 years or older with histologically or cytologically confirmed adenocarcinoma of the pancreas that is inoperable or metastatic.
    Pazienti di ambo i sessi, di età pari o superiore a 18 anni, con adenocarcinoma del pancreas confermato istologicamente o citologicamente, non operabile o metastatico.
    E.1.1.1Medical condition in easily understood language
    Advanced pancreatic cancer
    Cancro pancreatico in stadio avanzato
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    E.1.2Level LLT
    E.1.2Classification code 10033606
    E.1.2Term Pancreatic cancer non-resectable
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    E.1.2Level LLT
    E.1.2Classification code 10033605
    E.1.2Term Pancreatic cancer metastatic
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate and compare the OS of subjects with advanced or metastatic adenocarcinoma of the pancreas when treated with ruxolitinib in combination with capecitabine versus capecitabine alone.
    Valutare e confrontare la sopravvivenza globale (overall survival, OS) di soggetti con adenocarcinoma del pancreas in stadio avanzato o metastatico trattati con ruxolitinib in associazione con capecitabina rispetto a capecitabina in monoterapia.
    E.2.2Secondary objectives of the trial
    To evaluate and compare the efficacy of the 2 treatment groups with respect to PFS.
    To evaluate and compare the efficacy of the 2 treatment groups with respect to overall tumor response and duration of response.
    To evaluate and compare the safety and tolerability of ruxolitinib in combination with capecitabine versus capecitabine alone.
    Valutare e confrontare l'efficacia dei 2 gruppi di trattamento in termini di sopravvivenza libera da progressione (progression free survival, PFS).
    Valutare e confrontare l'efficacia dei 2 gruppi di trattamento in termini di risposta complessiva del tumore e durata della risposta.
    Valutare e confrontare la sicurezza e la tollerabilità di ruxolitinib in associazione con capecitabina rispetto a capecitabina in monoterapia
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    •Male or female, 18 years or older.
    •Histologically or cytologically confirmed adenocarcinoma of the pancreas.
    •Advanced adenocarcinoma of the pancreas that is inoperable or metastatic.
    •mGPS of 1 or 2 as defined below:
    -mGPS of 1: C-Reactive protein >10 mg/L and albumin ≥ 35 g/L
    -mGPS of 2: C-Reactive protein >10 mg/L and albumin < 35 g/L
    •Received 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy).
    a.Use of a fluoropyrimidine-containing regimen (eg, FOLFIRNOX, FOLFOX, CapeOx, etc) in the first-line setting is permitted provided the subject discontinued treatment for reasons other than disease progression and the subject received ≤ 2 cycles of therapy. Subjects who received single-agent capecitabine as first-line therapy are not eligible.
    b. There is no restriction on the use of fluoropyrimidine-containing regimens in the neo-adjuvant or adjuvant setting.
    c. History of palliative radiotherapy to disease sites is allowed provided there are other sites of disease or subsequent progression of the disease in the radiation field, and ≥ 4 weeks have elapsed since the completion of radiotherapy and all treatment-related toxicities have resolved or are at a new stable baseline.

    •Able to tolerate and benefit from therapy as evidenced by:
    -Absolute neutrophil count ≥ 1.5 × 109/L with WBC < 20 × 109/L.
    -Platelets ≥ 75 × 109/L.
    -Hemoglobin ≥ 9 g/dL (transfusions are permitted to achieve baseline hemoglobin level).
    -Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN); or ≤ 5 × ULN in the presence of liver metastases.
    -Total bilirubin ≤ 1.5 × ULN; if total bilirubin is > 1.5 × ULN then direct bilirubin must be ≤ 1.5 × ULN.
    -Alkaline phosphatase < 3 × ULN.
    -Lactate dehydrogenase (LDH) < 3 × ULN in the absence of hemolysis.
    -Creatinine clearance ≥ 50 mL/min measured or calculated by Cockroft-Gault equation or the estimated glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m2 using the MDRD formula.
    -ECOG performance status 0 to 2.
    B-ody mass index (BMI) > 16 kg/m2.
    -Absence of significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral, or psychiatric disease.
    -Able to swallow and retain oral medication.
    •≥ 2 weeks elapsed from the completion of previous treatment regimen and subjects must have recovered or be at a new stable baseline from any related toxicities.
    •Radiographically measurable or evaluable disease (based on local evaluation).
    -Measurable lesions may be in the field of prior radiation; however, there must be at least a 4-week period between the last radiation treatment and demonstration of interval progression of the lesion compared with the baseline scan documenting disease status for the lesion to be considered measurable.
    •Females are either postmenopausal for at least 1 year with documented follicle-stimulating hormone (FSH) > 30 IU/L, are surgically sterile for at least 3 months, or must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through follow-up if of childbearing potential. (Note: Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subjects and their understanding confirmed). For all females, the pregnancy test result must be negative at screening.
    •Males must agree to take appropriate precautions to avoid fathering a child (with at least 99% certainty) from screening through follow-up. (Note: Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subjects and their understanding confirmed).
    •Ability to comprehend and willingness to sign an informed consent form (ICF).
    •Pazienti di ambo i sessi, di età pari o superiore ai 18 anni.
    •Adenocarcinoma del pancreas con conferma istologica o citologica.
    •Adenocarcinoma del pancreas in stadio avanzato non operabile o metastatico.
    •mGPS pari a 1 o 2 come definito di seguito:
    -mGPS pari a 1: proteina C reattiva >10 mg/l e albumina ≥35 g/l
    -mGPS pari a 2: proteina C reattiva >10 mg/l e albumina <35 g/l
    •Trattamento con 1 regime chemioterapico precedente per malattia in stadio avanzato o metastatico (non includendo terapia neoadiuvante e/o adiuvante).
    a.L'uso di un regime contenente fluoropirimidine (es. FOLFIRNOX, FOLFOX, CapeOx, ecc.) nel trattamento di prima linea è permesso, purché il soggetto abbia interrotto il trattamento per motivi diversi dalla progressione di malattia e purché il soggetto abbia ricevuto ≤ 2 cicli di terapia. I soggetti che hanno ricevuto capecitabina in monoterapia come terapia di prima linea non sono idonei.
    b.Non ci sono restrizioni all'uso di regimi contenenti fluoropirimidine come terapie neoadiuvante o adiuvante.
    c.La radioterapia palliativa nelle sedi del tumore è consentita, purché siano presenti altri siti della malattia o si sia avuta una successiva progressione della malattia nell’areadi irradiazione, siano trascorse ≥ 4 settimane dal completamento della radioterapia e tutte le eventuali tossicità correlate al trattamento si siano risolte o siano a un nuovo stato basale stabile.
    •Capacità di tollerare e trarre giovamento dalla terapia, come evidenziato dai parametri indicati di seguito.
    -Conta assoluta dei neutrofili ≥1,5 × 109/l con conta leucocitaria < 20 × 109/l.
    -Piastrine ≥ 75 × 109/l.
    -Emoglobina ≥9 g/dl (sono permesse trasfusioni per ottenere il livello basale di emoglobina).
    -ALT/AST ≤ di 2,5 volte il limite superiore della norma (LSN); o ≤ di 5 volte LSN in presenza di metastasi epatiche.
    -Bilirubina totale ≤di 1,5 volte LSN; se la bilirubina totale è >di 1,5 volte LSN, la bilirubina diretta deve essere ≤ di 1,5 volte LSN.
    -Fosfatasi alcalina < di 3 volte LSN.
    -Lattato deidrogenasi (LDH) < di 3 volte LSN in assenza di emolisi.
    -Clearance della creatinina misurata o calcolata mediante l'equazione di Cockroft-Gault ≥50 ml/min o tasso di filtrazione glomerulare (glomerular filtration rate, GFR) stimato ≥50 ml/min/1,73 m2 usando la formula di modificae della dieta nella malattia renale (Modification of Diet in Renal Disease, MDRD).
    -Stato della prestazione ECOG compreso tra 0 e 2.
    -Indice di massa corporea (body mass index, BMI) > 16 kg/m2.
    -Assenza di patologie concomitanti non controllate significative comprese, ma non solo, malattie renali, epatiche, ematologiche, gastrointestinali, endocrine, polmonari, cardiache, neurologiche, cerebrali o psichiatriche.
    -Capacità di ingerire e trattenere il farmaco orale.
    •Tempo trascorso ≥ 2 settimane dal completamento del regime terapeutico precedente e recupero dei soggetti da eventuali tossicità correlate o presenza di nuovo stato basale stabile.
    •Malattia misurabile o valutabile radiologicamente (in base alla valutazione locale).
    -Le lesioni misurabili possono trovarsi nell’area di irradiazione precedente; tuttavia, affinché la lesione sia ritenuta misurabile, deve essere trascorso un periodo di almeno 4 settimane dall'ultima radioterapia e dalla dimostrazione della progressione della lesione rispetto alla scansione basale che documenta lo stato di malattia.
    •Pazienti donne che sono in post- menopausa da almeno un anno con un valore di ormone follicolo stimolante (FSH) >30IU/L, o che sono sterilizzate chirurgicamente da almeno 3 mesi o, se potenzialmente fertili, che devono acconsentire ad assumere appropriate precauzioni per evitare una gravidanza (con una certezza di almeno il 99% ) dallo screening fino al follow-up. (nota:i metodi consentiti che sono efficaci almento al 99%nel prevenire una gravidanza devono essere comunicati alle pazienti e la loro comprensione deve essere confermata). Per tutte le donne, il test di gravidanza deve risultare negativo allo screening.
    •Pazienti maschi devono acconsentire a prendere appropriate precauzioni per evitare di generare dei figli (con una certezza del 99%) dallo screening finto al follow-up(nota:i metodi consentiti che sono efficaci almento al 99%nel prevenire una gravidanza devono essere comunicati ali pazienti e la loro comprensione deve essere confermata).
    •Abilità a comprendere un consenso informato e la volontà di firmarlo
    E.4Principal exclusion criteria
    • Received more than 1 prior chemotherapy regimen for advanced or metastatic disease.
    •Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
    •Known brain or central nervous system metastases or history of uncontrolled seizures.
    •Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy.
    •Ongoing radiation therapy, radiation therapy administered within 30 days of enrollment, or prior history of radiation therapy to ≥ 25% of the bone marrow
    •Subjects who received palliative radiation treatment to a limited field or on an accelerated schedule within the last 30 days are eligible for enrollment, provided at least 7 days have elapsed from completion of radiation therapy prior to the first dose and all treatment related toxicities have resolved or are at a new stable baseline.
    •Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization).
    •Subjects who participated in any other study in which receipt of an investigational study drug occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose.
    •Current or previous other malignancy within 2 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy without sponsor approval.
    •Recent (≤ 3 months) history or ongoing partial or complete bowel obstruction, unless due to the disease understudy and surgically corrected.
    •Prior severe reaction to fluoropyrimidines, known DPD deficiency, or other known sensitivity to 5-FU.
    •Known history of human immunodeficiency virus (HIV) infection.
    •Active hepatitis B or C infection that requires treatment.
    •Unwilling to be transfused with blood components.
    •Pregnant or breastfeeding women.
    •Subjects who, in the opinion of the investigator, are unable or unlikely to comply with the dosing schedule and study evaluations.
    •Any condition in the judgment of the investigator that would jeopardize the safety of the subject or compliance with the protocol.
    •Ricevimento di più di 1 regime chemioterapico precedente per malattia in stadio avanzato o metastatico.
    •Malattia infettiva cronica o in corso che richiede trattamento con antibiotici sistemici, antimicotici o antivirali.
    •Metastasi cerebrali o al sistema nervoso centrale accertate o anamnesi di convulsioni non controllate.
    •Cardiopatia clinicamente significativa compresi angina instabile, infarto miocardico acuto entro 6 mesi dal Giorno 1 della somministrazione del farmaco dello studio, insufficienza cardiaca congestizia di classe III o IV secondo la New York Heart Association e aritmia che richiede terapia.
    •Radioterapia in corso, radioterapia somministrata entro 30 giorni dall'arruolamento o precedente storia clinica di radioterapia a ≥25% del midollo osseo.
    -I soggetti che hanno ricevuto radioterapia palliativa in un’arealimitata o secondo uno schema accelerato negli ultimi 30 giorni sono idonei all'arruolamento, purché siano trascorsi almeno 7 giorni dal completamento della radioterapia prima della prima dose.
    •Terapia antitumorale concomitante (es. chemioterapia, radioterapia, intervento chirurgico, immunoterapia, terapia biologica, terapia ormonale, terapia sperimentale o embolizzazione tumorale).
    •Soggetti che hanno partecipato a un qualsiasi altro studio durante il quale un farmaco sperimentale è stato somministrato entro 28 giorni o 5 emivite (a seconda di quale sia temporalmente più lunga ) prima della prima dose.
    •Altra neoplasia maligna attuale o pregressa entro 2 anni dall'ingresso nello studio, ad eccezione di carcinoma a cellule basali o squamose, cancro alla vescica superficiale, neoplasia intraepiteliale prostatica, carcinoma in situ della cervice curati o altre neoplasie maligne non invasive o indolenti senza l'approvazione dello sponsor.
    •Recente (≤ 3 mesi) anamnesi o presenza attuale di ostruzione intestinale parziale o completa, salvo se dovuta alla malattia in esame e corretta chirurgicamente.
    •Precedente reazione grave alle fluoropirimidine, noto deficit di diidropirimidina deidrogenasi (DPD) o altra nota sensibilità al fluorouracile (5-FU).
    •Nota anamnesi di infezione da virus di immunodeficienza umana (human immunodeficiency virus, HIV).
    •Infezione da epatite B o C attiva che richiede trattamento.
    •Mancata volontà di sottoporsi a trasfusione con emocomponenti.
    •Donne in stato di gravidanza o in allattamento
    •Soggetti che, in accordo all’opinione dello sperimentatore, non sono in grado o è improbabile che rispettino lo schema di dosaggi e le valutazioni dello studio.
    •Qualsiasi condizione che a giudizio dello sperimantatore possano mettere a rischio la sicurezza del paziente o il rispetto del protocollo
    E.5 End points
    E.5.1Primary end point(s)
    Overall survival as determined from the date of randomization until death due to any cause.
    Sopravvivenza globale determinata dalla data della randomizzazione alla data del decesso per qualsiasi causa
    E.5.1.1Timepoint(s) of evaluation of this end point
    This study is event-driven and will complete when 262 deaths (combined across the 2 treatment groups) occur in the study, presuming that the study will not have been stopped earlier for futility, efficacy, or safety considerations.
    In this study, approximately 310 subjects will be randomized 1:1 between ruxolitinib and placebo over an approximate 18-month period. Assuming uniform accrual over the 18-month period, exponential survival on both placebo (median OS of 2 months) and ruxolitinib (median OS of 3 months), the targeted number of deaths is expected 2 months after the last subject starts treatment in the randomized portion of the study.
    Lo studio è basato su eventi e verrà completato quando si verificheranno 262 decessi nel corso dello studio (unendo i 2 gruppi di trattamento), supponendo che lo studio non sia stato fermato anticipatamenteper considerazioni di futilità, efficacia o sicurezza. In questo studio, circa 310 pazienti saranno randomizzati in rapporto 1:1 a ruxolitinib e placebo. In base a un arruolamento uniforme nel corso di un periodo di 18 mesi e un'OS distribuita esponenzialmente nei gruppi di trattamento con placebo (mediana OS di 2 mesi) e ruxolitinib (mediana OS di 3 mesi), si prevede che il numero previsto di decessi avvenga 2 mesi dopo l’inizio del trattamento nella fase di randomizzazione dello stuidio dell’ultimo paziente.
    E.5.2Secondary end point(s)
    Progression-free survival defined as the time from randomization until the earliest date of disease progression determined by investigator assessment of objective radiographic disease assessments per RECIST (v1.1), or death due to any cause, if sooner.

    Objective response rate and duration of response determined by radiographic disease assessments per RECIST (v1.1), by investigator assessment.

    Safety and tolerability of the treatment regimens through assessment of AEs and changes in safety assessments including laboratory parameters.
    •Sopravvivenza libera da progressione definita come il tempo trascorso dalla randomizzazione fino alla prima data della progressione di malattia determinata mediante l'esame dello sperimentatore delle valutazioni radiologiche obiettive della malattia ai sensi dei criteri RECIST (v1.1) o al decesso per qualsiasi causa, se si verifica prima.
    •Tasso di risposta obiettiva e durata della risposta determinati mediante valutazioni radiologiche della malattia ai sensi dei criteri RECIST (v1.1), in base all'esame dello sperimentatore.
    •Sicurezza e tollerabilità dei regimi di trattamento mediante la valutazione degli eventi avversi e delle variazioni nelle valutazioni di sicurezza, compresi i parametri di laboratorio
    E.5.2.1Timepoint(s) of evaluation of this end point
    This study is event-driven and will complete when 262 deaths (combined across the 2 treatment groups) occur in the study, presuming that the study will not have been stopped earlier for futility, efficacy, or safety considerations.
    In this study, approximately 310 subjects will be randomized 1:1 between ruxolitinib and placebo over an approximate 18-month period. Assuming uniform accrual over the 18-month period, exponential survival on both placebo (median OS of 2 months) and ruxolitinib (median OS of 3 months), the targeted number of deaths is expected 2 months after the last subject starts treatment in the randomized portion of the study.
    Lo studio è basato su eventi e verrà completato quando si verificheranno 262 decessi nel corso dello studio (unendo i 2 gruppi di trattamento), supponendo che lo studio non sia stato fermato anticipatamenteper considerazioni di futilità, efficacia o sicurezza. In questo studio, circa 310 pazienti saranno randomizzati in rapporto 1:1 a ruxolitinib e placebo. In base a un arruolamento uniforme nel corso di un periodo di 18 mesi e un'OS distribuita esponenzialmente nei gruppi di trattamento con placebo (mediana OS di 2 mesi) e ruxolitinib (mediana OS di 3 mesi), si prevede che il numero previsto di decessi avvenga 2 mesi dopo l’inizio del trattamento nella fase di randomizzazione dello stuidio dell’ultimo paziente.
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    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) Yes
    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 No
    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 concerned23
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA60
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    European Union
    Korea, Republic of
    New Zealand
    Taiwan
    Thailand
    United States
    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
    This study is event-driven and will complete when 262 deaths (combined across the 2 treatment groups) occur in the study, presuming that the study will not have been stopped earlier for futility, efficacy, or safety considerations.
    Lo studio è basato su eventi e verrà completato quando si saranno verificati nello studio 262 decessi (combinati per 2 gruppi di trattamento), supponendo che lo studio non venga concluso anticipatamente per considerazioni di futilità, efficacia o sicurezza.
    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.1.2.1Number of subjects for this age range: 140
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 170
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 310
    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
    Nessuno
    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 Decision2014-07-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-06-11
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2016-02-11
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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