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    Summary
    EudraCT Number:2015-004535-12
    Sponsor's Protocol Code Number:KO-TIP-001
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-06-01
    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 number2015-004535-12
    A.3Full title of the trial
    An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies with HRAS Mutations
    Studio in aperto di fase II su Tipifarnib nel trattamento dei tumori maligni non ematologici avanzati con mutazioni del gene HRAS.
    An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies with HRAS Mutations.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A research study to find out whether tipifarnib is safe and effective for the treatment of a type of cancer that has a specific genetic mutation and for which there is no curative therapy available
    Uno Studio di Ricerca per valutare se tipifarnib sia sicuro ed efficace per il trattamento di un tipo di tumore che ha una specifica mutazione genetica e per il quale non ci sono terapie disponibili
    A.3.2Name or abbreviated title of the trial where available
    An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies with HRAS Muta
    Studio in aperto di fase II su Tipifarnib nel trattamento dei tumori maligni non ematologici avanzat
    A.4.1Sponsor's protocol code numberKO-TIP-001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02383927
    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 pointHead of Clinical Operations
    B.5.3 Address:
    B.5.3.1Street Address55 Cambridge Parkway, Suite 101
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02142
    B.5.3.4CountryUnited States
    B.5.4Telephone number0016175883747
    B.5.5Fax number0016175883747
    B.5.6E-mailcarrie@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
    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 codeR115777
    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 number900
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Advanced Non-Hematological Malignancies with HRAS mutations
    Tumori maligni non ematologici avanzati con mutazioni del gene HRAS
    E.1.1.1Medical condition in easily understood language
    A type of cancer that has a specific genetic mutation and for which there is no curative therapy available
    Tipo di tumore caratterizzato da una mutazione specifica per il quale non esistono trattamenti disponibili
    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 10066474
    E.1.2Term Thyroid cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10048683
    E.1.2Term Advanced cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level PT
    E.1.2Classification code 10071971
    E.1.2Term H-ras gene mutation
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    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 antitumor activity in terms of ORR of tipifarnib in subjects with locally advanced unresectable or metastatic, relapsed and/or refractory, HRAS mutant non hematological malignancies
    Determinare l'attività antitumorale di tipifarnib in termini di tasso di risposta oggettiva (ORR), in soggetti con tumore non ematologico con mutazioni del gene HRAS, recidivante e/o refrattario, localmente avanzato non resecabile o metastatico.
    E.2.2Secondary objectives of the trial
    Safety and tolerability of tipifarnib in subjects with locally advanced unresectable or metastatic, relapsed and/or refractory, HRAS mutant non hematological malignancies.
    Sicurezza e tollerabilità di tipifarnib in soggetti con tumore non ematologico con mutazioni del gene HRAS, recidivante e/o refrattario, localmente avanzato non resecabile o metastatico.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    •Adults, with histologically or cytologically confirmed diagnosis of non-hematological malignancy for which there is no curative therapy available. Cohort 1 subjects with malignant thyroid tumors. Cohort 2 any subject with a non-hematological HRAS mutation in first stage of cohort 2. The second stage the subjects must have HNSCC. Cohort 3 will enroll subjects with SCCs with HRAS mutations other than HNSCC
    Tumor that carries a missense HRAS mutation
    Subject consents to provide at least 10 unstained tumor slides (or equivalent tumor tissue blocks) for retrospective testing of HRAS gene tumor status, including T81C polymorphism
    Subject has measurable disease according to RECIST v1.1 and has relapsed or is refractory to prior therapy.
    At least 2 weeks since the last systemic therapy or radiotherapy regimen prior to enrolment
    ECOG PS 0 or 1
    Acceptable liver function
    Acceptable renal function
    Acceptable hematologic status
    Female subjects must be either of non-child-bearing potential (surgically sterilized or at least 2 years post-menopausal); or If of child-bearing potential, subject must use an adequatea highly effective method of contraception
    Written and voluntary informed consent understood, signed and dated
    1.Il soggetto dovrà avere un’età almeno di 18 anni.
    2.Il soggetto dovrà avere una diagnosi di tumore non ematologico confermata istologicamente o citologicamente, per il quale non sono disponibili terapie curative.
    a. Nella coorte 1 verranno arruolati soggetti con carcinoma maligno della tiroide
    b. I soggetti con tumori non ematologici mutanti per il gene HRAS (ad eccezione dei tumori maligni della tiroide) che soddisfano i criteri di eleggibilità arruolati nella prima fase della coorte 2 (completata). Per poter essere arruolati nella seconda fase della coorte 2 e nella sua estensione, i soggetti devono avere un carcinoma HNSCC con mutazioni del gene HRAS.
    c. Nella coorte 3 verranno arruolati i soggetti con carcinomi SCC diversi dai carcinomi HNSCC
    3. Il soggetto ha un tumore che porta ad una mutazione missenso secondo una metodologia approvata dallo Sponsor. Lo stato HRAS può essere stato valutato sia nel tessuto tumorale primario che nella recidiva o nella metastatica.
    4. Il soggetto ha acconsentito a fornire almeno 10 vetrini non colorati con tessuto tumorale (o blocchetti di tessuto tumorale equivalenti) per le analisi retrospettive dello stato del gene HRAS del tumore, compresa la valutazione del polimorfismo T81C.
    5. Il soggetto ha malattia misurabile secondo i criteri RECIST v1.1 che è recidivante (progressione della malattia) o refrattaria alla terapia precedente.
    6. Almeno 2 settimane dall'ultimo regime terapico sistemico o radioterapico prima dell'arruolamento.
    7. Performance status ECOG di 0 o 1
    8. Funzionalità epatica accettabile
    09. Funzionalità renale accettabile
    10. Stato ematologico accettabile:
    11. I soggetti di sesso femminile devono essere o:
    a. in età non fertile (sterilizzate chirurgicamente o in menopausa da almeno 2 anni); oppure se in età fertile, devono utilizzare un metodo di controllo delle nascite altamente efficace,
    12. Consenso informato scritto e volontario co
    E.4Principal exclusion criteria
    Prior treatment with an FTase inhibitor
    History of relevant coronary heart disease or myocardial infarction within last 3 years, NYHA Grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or serious cardiac arrhythmia requiring medication except atrial fibrillation. Known uncontrolled brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 4 weeks prior to Cycle 1 Day 1). Controlled brain metastases that require continuous high dose corticosteroid use within 4 weeks of Day 1.
    Non-tolerable >= Grade 2 neuropathy or evidence of emerging or rapidly progressing neurological symptoms within 4 weeks first dose. Non-tolerable grade 2 toxicities are defined as those with moderate symptoms that the patient is not able to endure for the conduct of instrumental activities of daily life or that persists = 7 days
    Major surgery, other than diagnostic surgery, within 4 weeks prior to first dose, without complete recovery.
    Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Known infection with HIV, or an active infection with hepatitis B or hepatitis C
    Subjects who have exhibited allergic reactions to tipifarnib or structural compounds similar to tipifarnib or to the drug product excipients. This includes hypersensitivity to imidazoles, such as clotrimazole, ketoconazole, miconazole and others in this drug class. PatientsSubjects with hypersensitivity to these agents will be excluded from enrolment.
    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.
    The subject has legal incapacity or limited legal capacity.
    Significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol. Unwillingness or inability to comply with the study protocol for any reason.
    1. Precedente trattamento (almeno 1 ciclo completo) con un inibitore dell'FTasi.
    2. Ogni anamnesi di malattia coronarica clinicamente rilevante o di infarto del miocardio negli ultimi 3 anni, insufficienza cardiaca congestizia di grado III o superiore secondo la New York Heart Association (NYHA), accidente cerebrovascolare nell'anno precedente o grave aritmia cardiaca in corso che necessita di farmaci, ad eccezione della fibrillazione atriale.
    3. Metastasi cerebrali, leptomeningeali o epidurali conclamate, non controllate (fatta eccezione di quelle trattate e ben controllate per almeno 4 settimane prima del Ciclo 1 Giorno 1). Metastasi cerebrali controllate che richiedono l'uso continuo di elevati dosaggi di corticosteroidi entro 4 settimane dal Giorno 1.
    4. Neuropatia non tollerabile > Grado 2 o evidenza di sintomi neurologici emergenti o in rapida progressione entro 4 settimane dal Ciclo 1 Giorno 1. Le tossicità non tollerabili di grado 2 sono definite come tossicità con sintomi moderati che non permettono al soggetto di sopportare attività strumentali della vita quotidiana o che persistono per 7 o più giorni.
    5. Intervento chirurgico maggiore, diverso da un intervento chirurgico a scopo diagnostico, nelle 4 settimane che precedono il Giorno 1 del Ciclo 1, senza completo recupero.
    6. Infezioni batteriche, virali o fungine attive, non controllate, che necessitano di terapia sistemica. Infezione conclamata da HIV o infezione attiva da epatite B o epatite C.
    7. Soggetti che evidenziano reazioni allergiche al tipifarnib o a composti strutturali simili al tipifarnib o agli eccipienti del farmaco. Ciò comprende l'ipersensibilità ai prodotti imidazolici, quali clotrimazolo, ketoconazolo, miconazolo e altri prodotti appartenenti a questa classe. I soggetti con ipersensibilità a questi agenti verranno esclusi dall'arruolamento.
    8. Malattia concomitante o condizione che potrebbe interferire con lo svolgimento dello studio o che potrebbe, a giudizio dello Sperimentatore, costituire un rischio inaccettabile per il soggetto in questo studio.
    9. Il soggetto ha un'incapacità legale o una capacità legale limitata.
    10. Stato mentale significativamente alterato che potrebbe limitare la comprensione o l'ottenimento del consenso informato e la compliance con i requisiti di questo protocollo. Riluttanza o incapacità ad ottemperare alle indicazioni del protocollo dello studio per qualsiasi ragione.
    E.5 End points
    E.5.1Primary end point(s)
    Response assessments according to RECIST 1.1
    valutazione della risposta in accordo ai criteri RECIST 1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    At screening (4 weeks before the first study drug administration), at the end of cycle 2 and at approximately 8 week intervals thereafter until disease progression
    Allo screening (4 settimane prima della prima dose di farmaco in studio), alla fine del ciclo 2 e poi all'incirca ogni 8 settimane fino a progressione della malattia.
    E.5.2Secondary end point(s)
    Treatment-emergent adverse events (TEAE) and SAEs evaluated according to NCI CTCAE v.4.03
    Eventi avversi emersi dal trattamento (TEAE) ed eventi avversi seri valutati secondo i criteri NCI CTCAE v.4.03
    E.5.2.1Timepoint(s) of evaluation of this end point
    Comprehensive assessment of any apparent toxicity experienced by the subject will be performed throughout the course of the trial (at each study visit and as clinically needed), from the time of the subject’s signature of informed consent until 30 days from the final administration of the trial treatment or immediately before initiation of any other anticancer therapy, whichever comes first
    Sarà effettuata una valutazione complessiva di ogni tossicità apparente riscontrata dal soggetto lungo tutto il corso dello studio (ad ogni visita prevista dal protocollo e clinicamente indicata), dalla data della frima del consenso informato da parte del soggetto fino a 30 giorni dopo la somministrazione finale del farmaco in studio o immediatamente prima di qualsiasi trattamento anti-tumurale, in base a qualedi questi eventi si verifichi prima.
    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 No
    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) 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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA23
    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
    Korea, Democratic People's Republic of
    Korea, Republic of
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of this clinical study is defined as the day when the last remaining study subject in the trial completes the last Follow-up assessment no later than 12 months after the last study subject is enrolled in the study. Provisions will be made for the continuation of study treatment in patients who demonstrate objective response or disease stabilization and manageable toxicity beyond the end of the study, e.g. a single patient treatment protocol
    La fine della sperimentazione è definita come il giorno in cui l'ultimo soggetto in studio completa le valutazioni previste per il Follow-Up, che non sarà oltre i 12 mesi dall'arruolamento dell'utlimo soggetto in studio. Saranno valutate opzioni per la continuazione del trattamento nei pazienti che dimostrano una risposta obiettiva o stabilità di malattia e tossicità accettabile, quali protocollo di trattamento individuale.
    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 years5
    E.8.9.2In all countries concerned by the trial months3
    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: 52
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 31
    F.4.2.2In the whole clinical trial 62
    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 Decision
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-07-19
    P. End of Trial
    P.End of Trial StatusCompleted
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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