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    Summary
    EudraCT Number:2018-001437-40
    Sponsor's Protocol Code Number:KO-TIP-007
    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:2020-11-04
    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 number2018-001437-40
    A.3Full title of the trial
    The AIM-HN and SEQ-HN Study: A 2 Cohort, Non-comparative, Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC) with HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN)
    Studio AIM-HN e SEQ-HN: Studio cardine non comparativo, a 2 coorti, volto a valutare l’efficacia di tipifarnib in pazienti con carcinoma a cellule squamose della testa e del collo (HNSCC) con mutazioni HRAS (AIM-HN) e l’impatto delle mutazioni HRAS sulla risposta alle terapie sistemiche di prima linea per l’HNSCC (SEQ-HN)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The AIM-HN and SEQ-HN Study: A 2 Cohort Study to Evaluate the Safety and Efficacy of Tipifarnib in Patients with Head and Neck Cancer with HRAS Mutations (Cohort 1) and the Impact of HRAS Mutations on Response to Treatment (Cohort 2)
    Studio AIM-HN e SEQ-HN: Studio a 2 coorti volto a valutare la sicurezza e l’efficacia di tipifarnib in pazienti con tumore della testa e del collo con mutazioni HRAS (Coorte 1) e l'impatto delle mutazioni HRAS sulla risposta al trattamento (Coorte 2)
    A.3.2Name or abbreviated title of the trial where available
    NA
    NA
    A.4.1Sponsor's protocol code numberKO-TIP-007
    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 SponsorKURA ONCOLOGY INC
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportKura Oncology, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKura Oncology, Inc.
    B.5.2Functional name of contact pointClinical Trials Mailbox
    B.5.3 Address:
    B.5.3.1Street Address3033 Science Park Road, Suite 220
    B.5.3.2Town/ citySan Diego
    B.5.3.3Post codeCA 92121
    B.5.3.4CountryUnited States
    B.5.6E-mailprivacy@kuraoncology.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 nameTipifarnib 300 mg
    D.3.2Product code [R115777]
    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 INNTipifarnib
    D.3.9.1CAS number 192185-72-1
    D.3.9.2Current sponsor code089408
    D.3.9.3Other descriptive nameTIPIFARNIB
    D.3.9.4EV Substance CodeSUB22236
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    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.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 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 nameTipifarnib 100 mg
    D.3.2Product code [R115777]
    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 INNTipifarnib
    D.3.9.1CAS number 192185-72-1
    D.3.9.2Current sponsor code089408
    D.3.9.3Other descriptive nameTIPIFARNIB
    D.3.9.4EV Substance CodeSUB22236
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
    (HNSCC) with HRAS Mutations
    Carcinoma a cellule squamose della testa e del collo (HNSCC) ricorrente o metastatico con mutazioni di HRAS
    E.1.1.1Medical condition in easily understood language
    Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
    (HNSCC) with HRAS Mutations
    Carcinoma a cellule squamose della testa e del collo (HNSCC) ricorrente o metastatico con mutazioni di HRAS
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10063569
    E.1.2Term Metastatic squamous cell carcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    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 ORR of tipifarnib in subjects with HNSCC with HRAS mutations as assessed by IRF.
    Determinare il tasso di risposta obiettiva (ORR) di tipifarnib in soggetti affetti da carcinoma squamocellulare della testa e del collo (HNSCC) con mutazioni di HRAS, valutato da una Struttura di revisione indipendente (IRF).
    E.2.2Secondary objectives of the trial
    -To determine the anti-tumor activity of tipifarnib in terms of: time to response, DOR, TTP, PFS, one year progression free rate, one year survival and OS
    -To investigate the safety and tolerability of tipifarnib according to the NCI CTCAE v5.0
    -To assess population PK of tipifarnib in subjects with HNSCC with HRAS
    mutations
    • Determinare l’attività antitumorale di tipifarnib in termini di: tempo alla risposta, durata della risposta (DR), tempo alla progressione (TTP), sopravvivenza libera da progressione (PFS), tasso di libertà da progressione a un anno, sopravvivenza a un anno e sopravvivenza complessiva (OS).
    • Analizzare la sicurezza e la tollerabilità di tipifarnib secondo i Criteri Comuni di Terminologia per gli Eventi Avversi del National Cancer Institute, versione 5.0 (NCI CTCAE v5.0).
    • Valutare la farmacocinetica (PK) di popolazione di tipifarnib in soggetti affetti da HNSCC con mutazioni di HRAS.
    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: Observational cohort SEQ-HN.
    Study title: The AIM-HN and SEQ-HN Study: A 2 Cohort, Non-comparative, Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC) with HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN).
    Objective of SEQ-HN is to help facilitate HRAS testing in HNSCC, preferentially as HNSCC patients initiate first line systemic treatment for recurrent or metastatic disease.

    Altre tipologie di sottostudi
    specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: La seconda coorte, SEQ-HN, è un sottostudio osservazionale.
    Titolo dello studio: Studio AIM-HN e SEQ-HN: Studio cardine non comparativo, a 2 coorti, volto a valutare l’efficacia di tipifarnib in pazienti con carcinoma a cellule squamose della testa e del collo (HNSCC) con mutazioni HRAS (AIM-HN) e l’impatto delle mutazioni HRAS sulla risposta alle terapie sistemiche di prima linea per l’HNSCC (SEQ-HN).
    L'obiettivo di SEQ-HN è contribuire ad agevolare l’analisi di HRAS nell’HNSCC, preferibilmente nel momento in cui i pazienti con HNSCC iniziano il trattamento sistemico di prima linea per malattia ricorrente o metastatica.
    E.3Principal inclusion criteria
    AIM-HN
    1.At least 18 years of age.
    2.Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Enrollment may proceed with local diagnosis but all subjects must consent to provide tumor tissue for a central pathology review.
    3.Documented tumor progression or recurrence from at least one prior platinum-containing regimen in the primary, neoadjuvant, adjuvant, advanced, recurrent or metastatic setting. Subjects must have progressed or have recurred from a prior platinum containing regimen but there is no limit in the number of prior lines of therapy. Subjects without prior platinum treatment who, at the judgment of the investigator, are considered unsuitable to receive standard therapy with a platinum-containing regimen due to auditory deficit or hypersensitivity to platinum may be also enrolled.
    4.Known tumor missense HRAS mutation with a variant allele frequency
    (VAF) > 20% according to Next Generation Sequencing (NGS) or any
    other methodology approved by the Sponsor. HRAS status may be assessed on tumor obtained at primary diagnosis or at later stages of disease. Enrollment may proceed with the identification of a missense HRAS mutation using a test preferred by the site and approved by the Sponsor but all subjects must consent to provide tumor tissue for central HRAS testing. Tumor tissue may be obtained from prior archival diagnostic
    biopsies. If no archival biopsy is available, a new biopsy will be required.
    5.Measurable disease by RECIST v1.1 that meets the criteria for selection as a target lesion according to RECIST v1.1. The presence of at least one measurable target lesion per RECIST v1.1 must be confirmed by local radiology prior to subject entry.
    6.At least 2 weeks since the last systemic therapy regimen prior to Cycle 1 Day 1. Subjects must have recovered to NCI CTCAE v5.0 < Grade 2 from all acute toxicities (excluding Grade 2 toxicities that are not considered a safety risk by the Sponsor and Investigator) or toxicity must be deemed irreversible by the Investigator.
    7.At least 2 weeks since last radiotherapy. Subjects must have recovered
    from all acute toxicities from radiotherapy.
    etc...

    SEQ-HN
    1.At least 18 years of age.
    2.Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology.
    3.HRAS wildtype (i.e. have no identified tumor missense HRAS mutation)
    determined by a test preferred by the site and approved by the Sponsor
    or through central HRAS testing. HRAS status may be assessed on tumor
    obtained at primary diagnosis or at later stages of disease.
    4.Will or has received at least one systemic anti-cancer therapy for recurrent or metastatic HNSCC for which there is available outcome information in terms of ORR, or the latter can be estimated based on the subject's records. Subjects who have not yet received or completed at least one systemic anti-cancer therapy for recurrent or metastatic HNSCC must consent to the collection of treatment outcome information and additional follow up contact in order to participate in the SEQ-HN portion of the study.
    etc...
    AIM-HN
    1. Età minima 18 anni.
    2. Conferma istologica di carcinoma della testa e del collo (della cavità orale, della faringe, della laringe, rinosinusale, rinofaringeo o primario non noto) a istologia squamosa non idoneo alla terapia locale con intento curativo (intervento chirurgico oppure radioterapia con o senza chemioterapia). L’arruolamento potrà procedere con la diagnosi locale, ma tutti i soggetti devono acconsentire a fornire del tessuto tumorale per una revisione istologica centrale.
    3. Progressione o recidiva tumorale documentata con almeno un precedente regime contenente platino nel contesto primario, neoadiuvante, adiuvante, avanzato, ricorrente o metastatico. I soggetti devono aver manifestato progressione o recidiva con un precedente regime contenente platino, ma non vi sono limiti nel numero di linee di terapia precedenti. Potranno inoltre essere arruolati soggetti non precedentemente sottoposti a un trattamento con platino che, a giudizio dello sperimentatore, sono ritenuti non idonei a ricevere la terapia standard con un regime contenente platino a causa di deficit uditivi o ipersensibilità al platino.
    4.Mutazione missenso di HRAS nota nel tumore con una frequenza della variante allelica (VAF) > 20% in base al sequenziamento di nuova generazione (Next Generation Sequencing - NGS) o a qualsiasi altra metodologia approvata dallo sponsor. Lo stato di HRAS può essere valutato sul tessuto tumorale prelevato per la diagnosi primaria o in stadi successivi della malattia. L’arruolamento potrà procedere con l’identificazione di una mutazione missenso di HRAS mediante un’analisi di preferenza del centro e approvata dallo sponsor, ma tutti i soggetti devono acconsentire a fornire del tessuto tumorale per l’analisi centrale di HRAS. Il tessuto tumorale può essere ottenuto da precedenti biopsie diagnostiche di archivio. Qualora non sia disponibile una biopsia d’archivio, sarà necessaria una nuova biopsia.
    5. Malattia misurabile secondo i criteri RECIST v1.1 che soddisfi i criteri per la selezione come lesione target in base ai RECIST v1.1. La presenza di almeno una lesione target misurabile secondo i criteri RECIST v1.1 deve essere confermata mediante esame radiologico locale prima dell’arruolamento del soggetto.
    6. Decorso di almeno 2 settimane dall’ultimo regime terapeutico sistemico prima del Giorno 1 del Ciclo 1. Tutte le tossicità acute presentate dai soggetti devono essere tornate a un Grado < 2 secondo i criteri NCI CTCAE v5.0 (escluse le tossicità di Grado 2 che non siano considerate un rischio per la sicurezza dallo sponsor e dallo sperimentatore) oppure la tossicità deve essere ritenuta irreversibile dallo sperimentatore.
    7. Decorso di almeno 2 settimane dall’ultima radioterapia. I soggetti devono essersi ripresi da tutte le tossicità acute dovute alla radioterapia.
    etc...

    SEQ-HN
    1. Età minima 18 anni.
    2. Conferma istologica di carcinoma della testa e del collo (della cavità orale, della faringe, della laringe, rinosinusale, rinofaringeo o primario non noto) a istologia squamosa.
    3. HRAS wild-type (ovvero, nessuna mutazione missenso di HRAS nel tumore identificata) stabilito attraverso un’analisi di preferenza del centro e approvata dallo sponsor oppure tramite l’analisi centrale di HRAS. Lo stato di HRAS può essere valutato sul tessuto tumorale prelevato per la diagnosi primaria o in stadi successivi della malattia
    4. Il soggetto riceverà o ha ricevuto almeno una terapia antitumorale sistemica per HNSCC ricorrente o metastatico per la quale siano disponibili informazioni sull’esito in termini di ORR o sia possibile stimare quest’ultimo in base alla documentazione del soggetto. Per partecipare alla porzione SEQ-HN dello studio, i soggetti che non hanno ancora ricevuto o completato almeno una terapia antitumorale sistemica per HNSCC ricorrente o metastatico devono acconsentire alla raccolta di informazioni sull’esito terapeutico e al contatto per l’ulteriore follow-up.
    etc...
    E.4Principal exclusion criteria
    AIM-HN
    1.Has disease that is suitable for local therapy administered with
    curative intent.
    2.Histologically confirmed salivary gland, thyroid, (primary) cutaneous
    squamous or nonsquamous histologies (e.g. mucosal melanoma).
    3.Known additional malignancy that is progressing or requires active
    treatment (excluding non-melanoma skin cancer, adjuvant hormonal
    therapy for breast cancer and hormonal treatment for castration
    sensitive prostate cancer).
    4.Ongoing treatment with an anticancer agent not contemplated in this
    protocol (excluding adjuvant hormonal therapy for breast cancer and
    hormonal treatment for castration sensitive prostate cancer).
    5.Prior treatment (at least 1 full treatment cycle) with a
    farnesyltransferase inhibitor (FTI).
    6.Any use of investigational therapy within 2 weeks of Cycle 1 Day 1 or 5
    half-lives (whichever is longer).
    7.Received treatment for unstable angina within prior year, myocardial
    infarction within the prior year, cerebro-vascular attack within the prior
    year, history of New York Heart Association grade III or greater
    congestive heart failure, or current serious cardiac arrhythmia requiring
    medication except atrial fibrillation.
    8.Non-tolerable Grade 2 or = Grade 3 neuropathy or evidence of unstable
    neurological symptoms within 4 weeks of Cycle 1 Day 1. Non-tolerable
    Grade 2 toxicities are defined as those with moderate symptoms that the
    subject is not able to endure for the conduct of instrumental activities of
    daily life or that persists = 7 days.
    9.Major surgery, other than diagnostic surgery, within 2 weeks prior to
    Cycle 1 Day 1, without complete recovery.
    10.Active, uncontrolled bacterial, viral or fungal infections requiring
    systemic therapy. Known history of infection with human
    immunodeficiency virus or an active infection with hepatitis B or
    hepatitis C.
    11. Received treatment for non-cancer related liver disease (excluding
    cholelithiasis) within prior year.
    12.Subjects who have exhibited allergic reactions to tipifarnib or
    structural compounds similar to tipifarnib or to its excipients. This
    includes hypersensitivity to imidazoles, such as clotrimazole,
    ketoconazole, miconazole and others in this drug class. Subjects with
    hypersensitivity to these agents will be excluded from enrollment.
    13.Required use of concomitant medications classified as strong
    inhibitors or inducers of cytochrome P450 3A4 (CYP3A4, Table 7) or
    UDP-glucuronosyltransferase (UGT).
    14.Concomitant disease or condition that could interfere with the
    conduct of the study or that would, in the opinion of the investigator,
    pose an unacceptable risk to the subject in this study.
    15.Dementia or significantly altered mental status that would limit the
    understanding or rendering of informed consent by the subject and compliance with the
    requirements of this protocol. Unwillingness or inability to comply with
    the study protocol for any reason.
    16.The subject has legal incapacity or limited legal capacity.

    SEQ-HN
    1.Histologically confirmed salivary gland, thyroid, (primary) cutaneous
    squamous or nonsquamous histologies (e.g. mucosal melanoma).
    2.Concomitant disease or condition that could interfere with the conduct
    of the study or that would, in the opinion of the investigator, pose an
    unacceptable risk to the subject in this study.
    3.The subject has legal incapacity or limited legal capacity.
    AIM-HN
    1. Presenza di malattia idonea alla terapia locale somministrata con intento curativo.
    2. Conferma istologica di carcinoma delle ghiandole salivari, della tiroide e cutaneo (primario) a istologia squamosa o non squamosa (per es. melanoma mucosale).
    3. Ulteriore malignità nota in fase progressiva o che richiede un trattamento attivo (tranne i tumori cutanei non melanomatosi, la terapia ormonale adiuvante per tumore mammario e il trattamento ormonale per tumore prostatico sensibile alla castrazione).
    4. Trattamento in corso con un agente antitumorale non contemplato nel presente protocollo (tranne la terapia ormonale adiuvante per tumore mammario e il trattamento ormonale per tumore prostatico sensibile alla castrazione).
    5. Precedente trattamento (almeno 1 ciclo completo di trattamento) con un inibitore della farnesil-transferasi (FTI).
    6. Impiego di una qualsiasi terapia sperimentale nelle 2 settimane precedenti il Giorno 1 del Ciclo 1 o entro 5 emivite (a seconda di quale dei due periodi abbia durata maggiore).
    7. Assunzione di un trattamento per angina instabile nell’anno precedente, infarto miocardico nell’anno precedente, attacco cerebrovascolare nell’anno precedente, anamnesi di insufficienza cardiaca congestizia di grado = III secondo la New York Heart Association o attuale aritmia cardiaca grave che richiede l’uso di farmaci, esclusa la fibrillazione atriale.
    8. Neuropatia non tollerabile di Grado 2 o Grado = 3 oppure evidenza di sintomi neurologici instabili nelle 4 settimane precedenti il Giorno 1 del Ciclo 1. Per tossicità di Grado 2 non tollerabili si intendono quelle con sintomi moderati che il soggetto non è in grado di tollerare per la conduzione di attività strumentali della vita quotidiana o che persistono per = 7 giorni.
    9. Intervento chirurgico maggiore, diverso da quelli a scopo diagnostico, nelle 2 settimane precedenti il Giorno 1 del Ciclo 1, senza recupero completo.
    10. Infezioni batteriche, virali o micotiche non controllate in fase attiva che richiedono una terapia sistemica. Anamnesi nota di infezione da virus dell’immunodeficienza umana o infezione attiva da virus dell’epatite B o dell’epatite C.
    11. Assunzione di un trattamento per epatopatia non correlata al tumore (esclusa la colelitiasi) nell’anno precedente.
    12. Soggetti che hanno manifestato reazioni allergiche a tipifarnib o a composti strutturali simili a tipifarnib, oppure ai suoi eccipienti. Sono incluse le reazioni di ipersensibilità agli imidazoli, quali clotrimazolo, ketoconazolo, miconazolo e altri agenti della stessa classe farmacologica. I soggetti con ipersensibilità a questi agenti saranno esclusi dall’arruolamento.
    13. Necessità di usare farmaci concomitanti classificati come forti inibitori o induttori del citocromo P450 3A4 (CYP3A4, Tabella 7) o della UDP-glucuronosiltransferasi (UGT).
    14. Malattia o condizione concomitante che potrebbe interferire con la conduzione dello studio o che, secondo il parere dello sperimentatore, comporterebbe un rischio inaccettabile per il soggetto in questo studio.
    15. Demenza o stato mentale significativamente alterato che potrebbe limitare la comprensione o il rilascio del consenso informato da parte del soggetto partecipante allo studio e la conformità ai requisiti del presente protocollo. Riluttanza o incapacità di conformarsi al protocollo di studio per qualsiasi motivo.
    16. Il soggetto presenta incapacità giuridica o capacità giuridica limitata.

    SEQ-HN
    1. Conferma istologica di carcinoma delle ghiandole salivari, della tiroide e cutaneo (primario) a istologia squamosa o non squamosa (per es. melanoma mucosale).
    2. Malattia o condizione concomitante che potrebbe interferire con la conduzione dello studio o che, secondo il parere dello sperimentatore, comporterebbe un rischio inaccettabile per il soggetto in questo studio.
    3. Il soggetto presenta incapacità giuridica o capacità giuridica limitata.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the proportion of subjects with confirmed Objective Response (OR), defined as either Complete Response (CR) or Partial Response (PR), calculated using the mITT analysis set.
    L’endpoint primario è la percentuale di soggetti con risposta obiettiva (OR) confermata, definita come risposta completa (CR) o risposta parziale (PR), calcolato usando la serie di analisi Intent-to-Treat modificata (mITT).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Tumor response assessment visit
    Visita di Valutazione della risposta del tumore
    E.5.2Secondary end point(s)
    •Time to response
    •Duration of response (DOR)
    •Time to progression (TTP)
    •Progression-free survival (PFS)
    •1-year progression-free rate and 1-year survival rate
    •Overall survival rate (OS)
    •Adverse Events
    •Population PK parameters of tipifarnib
    •Laboratory test results
    •Vital Signs
    •ECG results
    •Tempo alla risposta
    •Durata della risposta (DOR)
    •Tempo alla progressione (TTP)
    •Sopravvivenza senza progressione (PFS)
    •Tasso di mancanza di progressione a 1 anno e tasso di sopravvivenza a 1 anno
    •Tasso di sopravvivenza complessiva (OS)
    •Eventi avversi
    •Parametri di farmacocinetica (PK) di tipifarnib nella popolazione
    •Risultati dei test di laboratorio
    •Segni vitali
    •Risultati dell’ECG
    E.5.2.1Timepoint(s) of evaluation of this end point
    Tumor response assessment visit
    End of response assessment visit
    Follow up visit
    Visita di valutazione della risposta del tumore
    Visita di valutazione della fine della risposta
    Visita di follow-up
    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 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 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 No
    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.8.2.4Number of treatment arms in the trial1
    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 Yes
    E.8.5.1Number of sites anticipated in the EEA51
    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
    Australia
    Austria
    Belgium
    Canada
    Denmark
    France
    Germany
    Greece
    Italy
    Malaysia
    Netherlands
    Norway
    Taiwan
    Thailand
    United Kingdom
    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
    The end of this clinical study is defined as 2 years from enrollment of the last enrolled study subject in AIM-HN. If the last enrolled study subject discontinues treatment within 2 years of study enrollment, the End of Study will occur no earlier than the date of the last enrolled
    subject's safety follow-up assessment (End of Treatment visit) performed approximately 30 days after treatment discontinuation or until initiation of another anti-cancer therapy, whichever occurs first.
    La conclusione è definita come 2 anni dopo l’arruolam dell’ultimo soggetto dello studio in AIM-HN. Se l’ultimo sogg arruolato interrompe il trattamento entro 2 anni dall’arruolamento, la conclusione avrà luogo non prima della data della valutazione di follow-up di sicurezza (visita di fine trattamento) dell’ultimo soggetto arruolato, eseguita circa 30 giorni dopo l’interruzione del trattamento o fino all’inizio di un’altra terapia antitumorale, a seconda di quale evento si verifichi per primo.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    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 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: 84
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 200
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 152
    F.4.2.2In the whole clinical trial 284
    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 Decision2019-05-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-02-26
    P. End of Trial
    P.End of Trial StatusOngoing
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