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    Summary
    EudraCT Number:2018-001991-39
    Sponsor's Protocol Code Number:NIR-DT-301
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-01-27
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2018-001991-39
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Nirogacestat
    Versus Placebo in Adult Patients with Progressing Desmoid Tumors/Aggressive Fibromatosis
    (DT/AF)
    Sperimentazione randomizzata, in doppio cieco, controllata con placebo,
    di Fase 3 di Nirogacestat rispetto a placebo in pazienti adulti con tumori
    desmoidi / fibromatosi aggressiva (DT/AF) in progressione.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis
    Nirogacestat per pazienti adulti con tumori desmoidi / fibromatosi aggressiva
    A.3.2Name or abbreviated title of the trial where available
    DeFi
    DeFi
    A.4.1Sponsor's protocol code numberNIR-DT-301
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03785964
    A.5.4Other Identifiers
    Name:INDNumber:138207
    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 SponsorSpringWorks Therapeutics
    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 supportSpringWorks Therapeutics
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSpringWorks Subsidiary 2, PBC
    B.5.2Functional name of contact pointClinical Operations
    B.5.3 Address:
    B.5.3.1Street Address575 5th Avenue
    B.5.3.2Town/ cityNew York
    B.5.3.3Post codeNY 10017
    B.5.3.4CountryUnited States
    B.5.6E-mailclinical@springworkstx.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 nameNirogacestat
    D.3.2Product code [PF-03084014]
    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 INNNIROGACESTAT
    D.3.9.2Current sponsor codePF-03084014
    D.3.9.4EV Substance CodeSUB188628
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 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
    Desmoid Tumors/Aggressive Fibromatosis
    Tumori desmoidi / Fibromatosi aggressiva
    E.1.1.1Medical condition in easily understood language
    Desmoid Tumors/Aggressive Fibromatosis
    Tumori desmoidi / Fibromatosi aggressiva
    E.1.1.2Therapeutic area Diseases [C] - Skin and Connective Tissue Diseases [C17]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10059353
    E.1.2Term Desmoid tumor
    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
    To determine the efficacy (as defined by progression free survival [PFS])
    of nirogacestat in adult participants with progressing DT/AF.
    Determinare l’efficacia (definita in base alla sopravvivenza libera da progressione [progression free survival, PFS])
    di nirogacestat in partecipanti adulti con TD/FA in fase progressiva
    E.2.2Secondary objectives of the trial
    To evaluate the safety and tolerability of nirogacestat in adult
    participants with progressing DT/AF as measured by the incidence of
    adverse events (AEs);
    To determine the overall response rate (complete response [CR] +
    partial response [PR]) of nirogacestat in participants with progressing
    DT/AF;
    To determine the duration of response;
    To compare tumor volume changes measured by MRI in participants with
    progressing DT/AF;
    To evaluate desmoid tumor symptoms and impacts using patient reported
    outcomes (PROs).
    Valutare la sicurezza e la tollerabilità di nirogacestat in partecipanti adulti
    con TD/FA in fase progressiva, misurate in base all’incidenza
    di eventi avversi (EA);
    Determinare il tasso di risposta complessiva (risposta completa [RC] +
    risposta parziale [RP]) di nirogacestat nei partecipanti con TD/FA in fase progressiva;
    Determinare la durata della risposta;
    Confrontare le variazioni nel volume tumorale misurate mediante RM nei partecipanti
    con TD/FA in fase progressiva;
    Valutare i sintomi e gli impatti dei tumori desmoidi usando
    esiti riferiti dal paziente (patient-reported outcome, PRO).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Participant must be at least 18 years of age at the time of signing the informed consent (ICF). 2.Participant has DT/AF that progressed by (=20% measured by RECIST v1.1 within 12-month period prior to first dose of study treatment (nirogacestat or placebo). 3.Participant has: Newly diagnosed, measurably progressing DT/AF not amenable to surgical resection or radiation therapy; Recurrent, progressing DT/AF following CR to initial therapy; Preexisting DT/AF and has previously received therapy and residual tumor has progressed. 4.Participant agrees to provide archival or new tumor tissue for confirmation of disease. 5.If participant was previously treated with an investigational therapy for treatment of DT/AF,participant must have completed prior therapy at least 28 days prior to signing ICF.All toxicities from prior therapy must resolve to Grade 1 or baseline. 6.Participants who are receiving NSAIDs for conditions other than DT/AF must be receiving them prior to observed progression (inclusion criteria 2) for: Chronic scheduled daily use (defined as stable for 28 days prior to signing ICF); or Occasional use (defined as =3 days per week) for the treatment of pain or as anti-inflammatory in licensed conditions such as headache, arthritis, etc. 7.Participant has ECOG performance status ¿2 at screening (refer to Section 10.8 for ECOG performance status scale). 8.Participant has adequate organ and bone marrow function as defined by following Screening laboratory values: Absolute neutrophil count =1500 cells/µL; Platelets =100,000µL; Hemoglobin =9 g/dL; Total bilirubin =1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%); e.AST/ALT =2 ULN; f.Serum creatinine =1.5 x ULN or if creatinine >1.5 x ULN then calculated creatinine clearance must be =60 mL/min/1.73 m2 (using the CockcroftGault formula); 9.Participant can swallow tablets and has no gastrointestinal conditions affecting absorption. 10Male or Female. Contraceptive use by men women should be consistent with local regulations regarding the methods of contraception in clinical studies. a.Male participants: Male participants are eligible to participate if they agree to the following during the treatment period and for at least 90 days after the last dose of study treatment: Refrain from donating or preserving sperm; PLUS either: Be abstinent from sexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; OR Must agree to contraception/barrier as detailed below: Agree to use double-barrier contraception method when having sexual intercourse with a woman of childbearing potential (WOCBP). Additional contraception form should be used by WOCBP partner . b.Female participants:A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a WOCBP. OR Is WOCBP using 1 highly effective contraceptive method during treatment and until 6 months after the last dose of active study treatment . A second contraceptive method is required if the participant is using hormonal method. Additionally participant agrees not to donate eggs (ova, oocytes) for reproduction during treatment period and for at least 6 months after the last dose of study treatment. A WOCBP must have negative serum pregnancy test at screening and negative urine pregnancy test at baseline visit prior to first dose of study treatment. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with early undetected pregnancy. 11.Capable of giving signed ICF as described in Section 10.1.3 which includes compliance with requirements and restrictions listed in the ICF and in protocol
    1. Il partecipante deve avere almeno 18 anni alla firma del consenso informato (ICF)
    2. Il partecipante ha TD/FA in progressione (=20% misurata in base a RECIST v1.1 entro i 12 mesi precedenti la prima dose del trattamento di studio (nirogacestat o placebo).
    3. Il partecipante ha: TD/FA in progressione misurabile, di nuova diagnosi non trattabile chirurgicamente o con radioterapia
    TD/FA in progressione, recidivante in seguito a risposta completa a terapia iniziale
    TD/FA preesistente già trattata e in cui il tumore residuo ha progredito
    4. Il partecipante acconsente a dare tessuto tumorale nuovo o già archiviato per confermare la diagnosi
    5. Il partecipante che ha avuto precedente trattamento sperimentale per TD/FA, deve averlo completato almeno 28 giorni prima di firmare ICF.
    Tutte le tossicità causate dalla terapia devono essere risolte fino ad un grado 1 o tornate a livello basale
    6. I partecipanti in trattamento con FANS per condizioni diverse da TD/FA devono aver iniziato la terapia prima della progressione per:
    a. Trattamento giornaliero cronico (definito stabile nei 28 giorni prima di firma di ICF)
    b. Uso occasionale (=3giorni/settimana) per trattamento del dolore o per indicazioni autorizzate come mal di testa, artrite ecc.
    7. Il partecipante ha ECOG performance status =2 allo screening (sezione 10.8 per ECOG performance scale)
    8. Il partecipante ha adeguata funzione d’organo e del midollo osseo definita tramite i seguenti valori di laboratorio:
    a. Conta neutrofilica assoluta =1500 cellule/µL
    b. Piastrine = 100.000µL
    c. Emoglobina =9 g/dL
    d. Bilirubina totale =1.5 volte il limite normale superiore (ULN) (bilirubina isolata > 1.5 ULN è accettabile se la bilirubina è frazionata e la bilirubina diretta <35%)
    e. AST/ALT =2volte ULN e
    f. Creatinina serica =1.5 volte ULN o se la creatinina >1.5 volte ULN allora la clearance della creatinina deve essere =60 mL/min/1.73m2 (secondo formula Cockcroft-Gault)
    9. Il partecipante può deglutire pastiglie e non condizioni gastrointestinali che influiscono sull’assorbimento
    10. L’uso di contraccettivi maschili e femminili deve essere in accordo con le leggi locale sull’uso di contraccettivi nei trials clinici
    a. I maschi sono idonei se acconsentono durante il trattamento e per almeno 90 giorni successivi a ultima dose di trattamento di studio a:
    Astenersi dal donare o preservare sperma
    E
    Astenersi da rapporti sessuali, come preferito e usuale stile di vita (astinenza a lungo termine persistente) e acconsentire a continuare a praticare l’astinenza
    O
    Devono acconsentire all’utilizzo di metodi di contraccezione/barriera come descritto sotto:
    Acconsentire all’utilizzo di un metodo contraccettivo a doppia barriera quando hanno rapporti sessuali con donna potenzialmente fertile (WOCBP). La partner WOCBP dovrebbe usare un ulteriore metodo contraccettivo
    b. Una partecipante femmina è idonea se non è in gravidanza o allatta al seno, e almeno una di due condizioni sotto è soddisfatta.
    Non è una WOCBP
    O
    E’ una WOCBP e usa 1 metodo di contraccezione altamente efficace durante il trattamento e per almeno 6 mesi dopo l’ultima dose di trattamento di studio. un secondo metodo contraccettivo è richiesto in caso di metodo ormonale. la partecipante e acconsente a non donare oociti a fini riproduttivi durante il trattamento e per almeno 6 mesii dopo l’ultima dose di trattamento di studio. Una WOCBP deve avere test di gravidanza negativo su siero allo screening e su urina alla baseline prima della prima dose del trattamento di studio
    Lo sperimentatore è responsabile di valutare anamnesi, condizione mestruale e attività sessuale recente in modo da diminuire il rischio di arruolare una donna ai primi stadi di una gravidanza non rilevata
    11. Capace di dare il proprio consenso informato come descritto in sezione 10.1.3 che comprende l’ottemperanza ai requisiti e restrizioni elencate in ICF e nel protocollo
    E.4Principal exclusion criteria
    1. Participant has known malabsorption syndrome or preexisting
    gastrointestinal conditions that may impair absorption of nirogacestat
    (e.g., gastric bypass, lap band, or other gastric procedures); delivery of
    nirogacestat via nasogastric tube or gastrostomy tube is not allowed.
    2. Participant has experienced any of the following within 6 months of
    signing informed consent: clinically significant cardiac disease (New
    York Heart Association Class III or IV), myocardial infarction,
    severe/unstable angina, coronary/peripheral artery bypass graft,
    symptomatic congestive heart failure, cerebrovascular accident,
    transient ischemic attack, or symptomatic pulmonary embolism.
    3. Participant has abnormal QT interval corrected by Fridericia's formula
    (>450 msec for male participants, >470 msec for female participants, or
    >480 msec for participants with bundle branch block) after electrolytes
    have been corrected (triplicate ECG readings, done 2-3 minutes apart
    and averaged) at screening.
    4. Participant is using concomitant medications prolonging QT/QTcF of Class Ia and Class III, Non antiarrhytmics prolonging QT/QTcF are allowed if there are not additional Torsades de Pointes risk factors.
    5. Participant has congenital long QT syndrome.
    6. Lymphoma, leukemia, or any malignancy within the past 5 years
    except for basal cell or squamous epithelial carcinomas of the skin that
    have been resected with no evidence of metastatic disease for 3 years.
    7. Current or chronic history of liver disease or known hepatic or biliary
    abnormalities (except for Gilbert's syndrome or asymptomatic
    gallstones).
    8. Participant previously received or is currently receiving therapy with
    GS inhibitors or anti-Notch antibody therapy.
    9. Participant is currently using DT/AF treatment including TKIs, NSAIDs (chronic daily use except criterion 6) or IMPs 28 days prior first dose of study treatment
    or
    participant started any DT/AF treatment after documented progressive disease
    9. Participant is currently using or anticipates using food or drugs that
    are known strong/moderate cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 14 days prior to the first dose of study treatment.
    11. Participant is currently enrolled or was enrolled within 28 days of
    signing informed consent in another clinical study with any
    investigational drug or device; however, participation in observational
    studies is permitted.
    12. Participant has a positive human immunodeficiency virus antibody test.
    13. Participant has presence of Hepatitis B surface antigen at screening.
    14. Participant has a positive Hepatitis C antibody or Hepatitis C
    ribonucleic acid (RNA) test result at screening or within 3 months prior
    to starting study treatment.
    15. Participant is unable to tolerate MRI or for whom MRI is contraindicated.
    16. Participant with active or chronic infection at the time of informed consent and during the screening period.
    17. Participant has experienced other severe acute or chronic medical or
    psychiatric conditions, including recent (within 1 year of signing
    informed consent) or active suicidal ideation or behavior, or a laboratory
    abnormality that may increase the risk associated with study
    participation or study treatment administration or may interfere with the
    interpretation of study results and, in the judgment of the investigator,
    would make the participant inappropriate for entry into this study.
    18. participant has known hypersensitivity to the active substance or to excipients of nirogacestat or placebo
    19. Participant is unable to comply with study procedures
    1. Il partecipante soffre di sindrome da malassorbimento o condizioni gastrointestinali preesistenti che possono inficiare l’assorbimento di nirogacestat (come bypass gastrico, bendaggio gastrico o altre procedure gastriche); la somministrazione di nirogacestat tramite sonda nasogastrica o gastrostomia non è consentita
    2. Il partecipante ha avuto nei 6 mesi precedenti la firma di ICF uno dei seguenti: malattia cardiaca clinicamente significativa (NYHA Class III o IV), infarto del miocardio, angina severa/instabile, bypass arterioso coronarico/periferico, insufficienza cardiaca congestizia sintomatica, evento cerebrovascolare, attacco ischemico transiente, o embolia polmonare sintomatica.
    3. Il partecipante ha intervallo QT anormale corretto con Formula di Fridericia (<450 msec per i maschi, <470 msec per le femmine o <480 msec per partecipanti con blocco di branca) dopo correzione degli elettroliti (ECG triplicato, eseguito ad intervalli di 2-3 minuti e mediato) allo screening
    4. Il partecipante usa farmaci concomitanti che prolungano intervallo QT/QTcF di classe Ia e III. Non antiaritmici prolunganti intervallo QT/QTcF sono ammessi se non ci sono altri fattori di rischio per Torsades de Pointes
    5. Il partecipante ha sindrome da QT lungo congenita
    6. Linfoma, leucemia, o altra malignità nei 5 anni precedenti ad eccezione di basalioma e carcinoma epiteliale squamoso rimosso chirurgicamente senza evidenze di metastasi per 3 anni.
    7. Storia di malattia epatica attiva o cronica o diagnosi di anomalie epatiche o biliari (ad eccezione di sindrome di Gilbert o calcoli biliari)
    8. Il partecipante ha ricevuto in precedenza o è in terapia con inibitori di gamma secretasi o anticorpi anti Notch
    9. Il partecipante è in trattamento per DT/AF con TKI, FANS (uso cronico giornaliero, eccetto criterio 6) o IMPs 28 giorni precedenti la prima dose di trattamento di studio
    o
    Ha iniziato terapia per DT/AF dopo progressione documentata
    10. Il partecipante fa uso o ha usato alimenti o farmaci che sono moderati/forti inibitori o induttori di CYP3A4 (sezione 10.7) nei 14 giorni precedenti la prima dose del trattamento di studio
    11. Il partecipante è arruolato o è stato arruolato nei 28 giorni precedenti la firma di ICF in altra sperimentazione clinica con un qualsiasi farmaco sperimentale o dispositivo medico, la partecipazione a studi osservazionali è concessa.
    12. Il partecipante ha un test per anticorpi HIV (Human Immunodeficiency Virus) positivo
    13. Il partecipante ha presenza di antigene di superficie per l’epatite B allo screening
    14. Il partecipante ha un test per anticorpi Epatite C o un test per l’acido ribonucleico (RNA) dell’Epatite C positivo allo screening o nei 3 mesi precedenti l’inizio del trattamento di studio.
    15. Il partecipante non può tollerare la risonanza magnetica (RM) o per il partecipante la RM non è indicata
    16. Il partecipante con un’infezione attiva o cronica al momento del consenso informato e durante lo screening
    17. Il partecipante ha avuto altre malattie acute o croniche o condizioni psichiatriche, incluse recenti (entro 1 anno dalla firma di ICF) o in corso idee o comportamenti suicidi, o valori anormali di laboratorio che possono aumentare il rischio associato con la partecipazione allo studio o la somministrazione del trattamento di studio o possono interferire con l’interpretazione dei risultati dello studio e, a giudizio dello sperimentatore, rendono il partecipante non idoneo per entrare nello studio.
    18. Il partecipante ha ipersensitività nota al principio attivo o agli eccipienti di nirogacestat o placebo
    19. Il partecipante non è in grado di effettuare le procedure di studio
    E.5 End points
    E.5.1Primary end point(s)
    PFS defined as the time from randomization until the date of assessment
    of progression or death by any cause will be determined using Response
    Evaluation Criteria In Solid Tumors (RECIST) version (v)1.1 . The
    documented date of progression will be determined by an independent,
    blinded, central radiologic review.
    La PFS, definita come l’intervallo di tempo compreso tra la randomizzazione e la data di valutazione
    della progressione o decesso per qualsiasi causa, sarà determinata usando i Criteri di valutazione della risposta
    nei tumori solidi (RECIST) versione (v)1.1.
    La data documentata della progressione sarà determinata da una revisione
    radiologica centrale in cieco e indipendente.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Last patient last visit
    Last patient last visit
    E.5.2Secondary end point(s)
    Safety endpoints will include incidence of treatment-emergent AEs,
    changes in laboratory parameters, vital signs, physical examination
    findings, and electrocardiograms (ECGs).
    Tolerability will be assessed according to toxicities graded by National
    Cancer Institute Common Terminology Criteria for Adverse Events
    (CTCAE) v5.0;
    Overall response rate, defined as the proportion of participants with CR
    + PR assessed by RECIST v1.1 Criteria;
    Duration of response for participants whose best response is CR or PR;
    Change in tumor volume from baseline as assessed by MRI volumetric;
    Symptoms and impacts will be assessed by evaluating change from
    baseline on the following PROs:
    Memorial Sloan Kettering/Desmoid Tumor Research Foundation Desmoid
    Tumor Symptom Scale (MSK/DTRF DTSS);
    Brief Pain Inventory (BPI) short form;
    Patient-Reported Outcomes Measurement Information System Physical
    Function (PROMIS PF) short form 10a plus 3 additional items from
    PROMIS item banks;
    Memorial Sloan Kettering/Desmoid Tumor Research Foundation Desmoid
    Tumor Impact Scale (MSK/DTRF DTIS); and
    European Organisation for Research and Treatment of Cancer Quality of
    Life Questionnaire-Core 30 (EORTC) QLQ-C30.
    Gli endpoint di sicurezza includeranno incidenza di EA emergenti dal trattamento, variazioni nei parametri di laboratorio, segni vitali, risultati dell’esame obiettivo ed elettrocardiogrammi (ECG).
    La tollerabilità sarà valutata in base alle tossicità classificate secondo i Criteri terminologici comuni per gli eventi avversi (Common Terminology Criteria for Adverse Events, CTCAE) v5.0 del National Cancer Institute.
    Tasso di risposta complessiva, definito come la percentuale di partecipanti con Risposta Completa (RC) + Risposta Parziale (RP) valutate in base ai criteri RECIST v1.1.
    Durata della risposta per i partecipanti la cui migliore risposta è RC o RP.
    Variazione nel volume tumorale rispetto al basale valutata mediante RM volumetrica e
    I sintomi e gli impatti saranno valutati determinando la variazione rispetto al basale sui seguenti PRO:
    • Scala dei sintomi dei tumori desmoidi del Memorial Sloan Kettering/Fondazione per la ricerca sui tumori desmoidi (Memorial Sloan Kettering/Desmoid Tumor Research Foundation Desmoid Tumor Symptom Scale, MSK/DTRF DTSS);
    • Modulo ridotto dell’inventario breve sul dolore (brief pain inventory, BPI);
    • Modulo breve 10a del Sistema di misurazione degli esiti riferiti dal paziente-Funzionalità fisiche (Patient-Reported Outcomes Measurement Information System Physical Function, PROMIS PF) più altre 3 voci della banca di voci PROMIS;
    • Scala dell’impatto dei tumori desmoidi (Desmoid Tumor Impact Scale, DTIS) del Memorial Sloan Kettering/Fondazione per la ricerca sui tumori desmoidi (MSK/DTRF); e
    Questionario principale a 30 voci sulla qualità della vita dell’Organizzazione europea per la ricerca e il trattamento dei tumori (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, EORTC QLQ-C30).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Last patient last visit
    Last patient last visit
    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 Yes
    E.6.11Pharmacogenomic Yes
    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 No
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    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
    Canada
    United States
    Belgium
    Germany
    Italy
    Netherlands
    United Kingdom
    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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    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 years4
    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: 99
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 34
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 54
    F.4.2.2In the whole clinical trial 135
    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)
    Eligible participants may enroll in the optional Open-label phase to
    receive 150 mg BID of nirogacestat (open-label study treatment),
    continuously in 28-day cycles.
    Pazienti elegibili potrebbero essere arruolati in una fase in aperto opzionale ricevendo 150 mg BID di nirogacestat (trattamento in studio in aperto), continuativamente per cicli di 28 giorni
    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 Decision2019-07-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-11-27
    P. End of Trial
    P.End of Trial StatusOngoing
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