Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43974   clinical trials with a EudraCT protocol, of which   7312   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2019-004070-26
    Sponsor's Protocol Code Number:BRICE
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2021-06-08
    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 number2019-004070-26
    A.3Full title of the trial
    A Phase 1/2 Study Exploring Safety, Tolerability and Efficacy of BRIgatinib in Combination With CEtuximab in Subjects With Advanced EGFR mutated or ALK or ROS1 positive Non-Small Cell Lung Cancer and Expansion Phase in Subjects with Advanced EGFR mutated Non-Small Cell Lung Cancer who are resistant to EGFR tyrosine kinase inhibitors
    Studio di fase 1/2 che studia la sicurezza, la tollerabilità e l'efficacia di BRIgatinib in combinazione con CEtuximab in pazienti con carcinoma polmonare non a piccole cellule avanzato (NSCLC) con mutazioni di EGFR o positivi per riarrangiamento di ALK o ROS1 e fase di espansione in pazienti con NSCLC EGFR mutati resistenti agli inibitori tirosin-chinasici di EGFR (EGFR-TKI)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 1/2 Study Exploring Safety, Tolerability and Efficacy of BRIgatinib in Combination With CEtuximab in Subjects With Advanced EGFR mutated or ALK or ROS1 positive Non-Small Cell Lung Cancer and Expansion Phase in Subjects with Advanced EGFR mutated Non-Small Cell Lung Cancer who are resistant to EGFR tyrosine kinase inhibitors
    Studio di fase 1/2 che studia la sicurezza, la tollerabilità e l'efficacia di BRIgatinib in combinazione con CEtuximab in pazienti con carcinoma polmonare non a piccole cellule avanzato (NSCLC) con mutazioni di EGFR o positivi per riarrangiamento di ALK o ROS1 e fase di espansione in pazienti con NSCLC EGFR mutati resistenti agli inibitori tirosin-chinasici di EGFR (EGFR-TKI)
    A.3.2Name or abbreviated title of the trial where available
    BRICE
    BRICE
    A.4.1Sponsor's protocol code numberBRICE
    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 SponsorFONDAZIONE RICERCA TRASLAZIONALE (FORT)
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportTakeda Italia S.p.A
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationClinical Research Technology
    B.5.2Functional name of contact pointClinical Operations
    B.5.3 Address:
    B.5.3.1Street AddressPiazza Nicola Amore, 10
    B.5.3.2Town/ cityNapoli
    B.5.3.3Post code80138
    B.5.3.4CountryItaly
    B.5.4Telephone number08119572570
    B.5.5Fax number0897724155
    B.5.6E-mailbrice@cr-technology.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 nameALUNBRIG
    D.3.2Product code [Brigatinib]
    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.3.9.1CAS number 1197953-54-0
    D.3.9.2Current sponsor codeBrigatinib
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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 Yes
    D.2.1.1.1Trade name Erbitux
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Europe B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameErbitux
    D.3.2Product code [Cetuximab]
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCETUXIMAB
    D.3.9.1CAS number 205923-56-4
    D.3.9.2Current sponsor codeCetuximab
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeè un anticorpo monoclonale chimerico IgG prodotto in una linea cellulare di mammifero (Sp2/0) mediante tecniche di DNA ricombinante, diretto contro il recettore del fattore di crescita epidermico (EGF
    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 or metastatic epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC) with acquired resistance to approved EGFR tyrosine kinase inhibitors (TKI); advanced or metastatic ALK or ROS1 positive NSCLC with acquired resistance to specific available inhibitors.
    carcinoma polmonare non a piccole cellule (NSCLC) avanzato o metastatico positivo per la mutazione del recettore del fattore di crescita epidermico (EGFR) con resistenza acquisita agli inibitori tirosin chinasi della EGFR (TKI) approvati; NSCLC avanzato o metastatico positivo per ALK o ROS1 con resistenza acquisita a specifici inibitori disponibili.
    E.1.1.1Medical condition in easily understood language
    Advanced or metastatic epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC) with acquired resistance to approved EGFR tyrosine kinase inhibitors (TKI)
    NSCLC avanzato o metastatico positivo per la mutazione del recettore del fattore di crescita epidermico (EGFR) con resistenza acquisita agli inibitori tirosin chinasi della EGFR (TKI) approvati
    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 10061873
    E.1.2Term Non-small cell lung cancer
    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
    There are study two phases with different primary and secondary objectives.

    Primary objectives:
    · Phase 1: To evaluate the safety and tolerability and determine the maximum tolerated dose (MTD) or a pharmacologically active dose (PAD) of brigatinib in combination with cetuximab in patients with advanced EGFR mutation positive cancers and ALK or ROS1 positive tumors who are resistant to available inhibitors.
    · Phase 2: To evaluate the activity of brigatinib in combination with cetuximab in EGFR mutation positive NSCLC who develop an on-target mechanism of resistance, i.e. secondary or tertiary resistance mutations of EGFR (secondary/tertiary mutations of EGFR)
    Ci sono due fasi di studio con differenti obiettivi primari e secondari:
    Obiettivi Primari:
    Fase 1: Valutare la sicurezza e la tollerabilità e determinare la Massima Dose Tollerata (MTD) o la dose farmacologicamente attiva (PAD) del brigatinib in combinazione con il cetuximab in pazienti con carcinoma avanzato con mutazioni di EGFR o positivi per riarrangiamento di ALK o ROS1 che sono resistenti agli inibitori disponibili.
    Phase 2: Valutare l’attività del brigatinib in combinazione con il cetuximab in pazienti con carcinoma polmonare non a piccole cellule (NSCLC) con mutazioni di EGFR che hanno sviluppato meccanismi di resistenza ai farmaci a bersaglio molecolare EGFR-TKI, cioè mutazioni di resistenza secondarie o terziarie dell'EGFR.
    E.2.2Secondary objectives of the trial
    · Phase 1: To evaluate the activity of brigatinib in combination with cetuximab in patients with EGFR mutated solid tumors and ALK and ROS1 positive tumors that are resistant to available inhibitors.
    · Phase 2: To evaluate the safety and tolerability of brigatinib and cetuximab at the MTD or PAD in EGFR mutation positive NSCLC who develop an .on-target mechanism of resistance to available TKIs, i.e. secondary or tertiary resistance mutations of EGFR.
    · Phase 2: To evaluate the efficacy of brigatinib in combination with cetuximab in EGFR mutation positive NSCLC who develop a non-target mechanism of resistance to available TKIs, i.e. secondary or tertiary resistance mutations of EGFR.
    Fase 1: Valutare l’attività del brigatinib in combinazione con il cetuximab in pazienti con tumori solidi EGFR mutati e positivi ad ALK o ROS 1 che sono resistenti agli inibitori disponibili.
    Fase 2: Valutare la sicurezza e la tollerabilità del brigatinib e cetuximab alla MTD o PAD in pazienti con carcinoma polmonare non a piccole cellule (NSCLC) con mutazioni di EGFR che hanno sviluppato meccanismi di resistenza ai farmaci a bersaglio molecolare EGFR-TKI, cioè mutazioni di resistenza secondarie o terziarie dell'EGFR.
    Fase 2: Valutare l’efficacia del brigatinib in combinazione con il cetuximab in pazienti con carcinoma polmonare non a piccole cellule (NSCLC) con mutazioni di EGFR che hanno sviluppato meccanismi di resistenza ai farmaci a bersaglio molecolare EGFR-TKI, cioè mutazioni di resistenza secondarie o terziarie dell'EGFR.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion criteria Part 1 only
    1) Histologically confirmed advanced EGFR mutated or ALK positive or ROS1 positive tumors resistant to available specific inhibitors.
    Part 2 only
    1) Acquired resistance to EGFR TKIs defined as progression of disease according to RECIST 1.1 during osimertinib treatment and presence of on-target mechanism of resistance, i.e. secondary or tertiary resistance mutations of EGFR, on circulating tumor DNA or tumor tissue obtained before treatment start and after any intervening systemic treatment
    Parts 1 and 2
    1) Age 18 years or older
    2) Willingness to provide written informed consent.
    3) Life expectancy >12 weeks.
    4) ECOG performance status of 0 to 1.
    5) Presence of measurable disease per RECIST v1.1 as determined by the site study team. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. The lesion selected for pre- and/or post-treatment biopsy cannot be the only measurable lesion.
    6) Female patients should be using adequate contraceptive measures, should not be breastfeeding until 120 days after the last dose, and must have a negative pregnancy test (serum or urine) prior to first dose of study drug (within 72 hours); or female patients must have an evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
    a. Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
    b. Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution.
    c. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.
    Female patients must meet 1 of the following:
    • Postmenopausal for at least 1 year before the screening visit, or
    • Surgically sterile, or
    • If they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing of the informed consent form through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
    Brigatinib may decrease effectiveness of hormonal contraceptives, therefore, women are recommended to use non-hormonal methods of contraception. Highly effective non-hormonal birth control for women of child bearing potential with male partners includes:

    • Sexual abstinence (no sexual intercourse)
    • Intrauterine device (IUD) or intrauterine system (IUS)
    • Bilateral tubal ligation (both tubes tied)
    • Vasectomized partner
    7) Male patients should be willing to use barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or completely abstain from heterosexual intercourse
    Solo Fase 1
    Conferma istologica di tumori avanzati EGFR mutati o positivi per ALK o ROS1 resistenti agli inibitori specifici disponibili.
    Solo Fase 2
    Resistenza acquisita ai TKI dell'EGFR definita come progressione della malattia secondo RECIST 1.1 durante il trattamento con osimertinib e presenza di un meccanismo di resistenza on target, ad esempio mutazioni di resistenza secondarie o terziarie dell'EGFR, sul DNA tumorale circolante o sul tessuto tumorale ottenuto prima dell'inizio del trattamento e dopo qualsiasi trattamento sistemico.
    Parte 1 e 2
    1. Età = 18 anni.
    2. Disponibilità a fornire il consenso informato scritto.
    3. Aspettativa di vita > 12 settimane.
    4. ECOG performance status da 0 a 1.
    5. Presenza di malattia misurabile in accordo ai RECIST v1.1 come determinato dal team di studio del centro. Le lesioni tumorali situate in un'area precedentemente irradiata sono considerate misurabili se la progressione è stata dimostrata in tali lesioni. La lesione selezionata per la biopsia pre- e/o post-trattamento non può essere l'unica lesione misurabile.
    6. Le pazienti di sesso femminile devono utilizzare misure contraccettive adeguate, non devono allattare fino a 120 giorni dopo l'ultima dose e devono avere un test di gravidanza negativo (siero o urina) prima della prima dose del farmaco in studio (entro 72 ore); in alternativa le pazienti di sesso femminile devono avere un’evidenza di potenziale non fertilità soddisfacendo uno dei seguenti criteri allo screening:
    a) Stato post-menopausale definito come età superiore a 50 anni e amenorrea per almeno 12 mesi dopo la cessazione di tutti i trattamenti ormonali esogeni.
    b) Donne sotto i 50 anni sono considerate in postmenopausa se sono state amenorroiche per 12 mesi o più dopo la cessazione dei trattamenti ormonali esogeni e con livelli di ormone luteinizzante (LH) e ormone follicolo-stimolante (FSH) nel range post-menopausale dell’ospedale.
    c) Documentata sterilizzazione chirurgica irreversibile mediante isterectomia, ovariectomia bilaterale o salpingectomia bilaterale ma non legatura delle tube.
    Le pazienti di sesso femminile devono soddisfare uno dei seguenti criteri:
    • Stato postmenopausale per almeno 1 anno prima della visita di screening, o
    • Sterilità Chirurga, o
    • Se in età fertile, utilizzo di 2 metodi contraccettivi efficaci dal momento della firma del modulo di consenso informato fino a 4 mesi dopo l'ultima dose del farmaco in studio, o accettare di astenersi completamente dai rapporti eterosessuali.
    Brigatinib può diminuire l'efficacia dei contraccettivi ormonali, pertanto si raccomanda alle donne di utilizzare metodi contraccettivi non ormonali. Il controllo delle nascite non ormonale altamente efficace per le donne in età fertile con partner maschili si può perseguire con:
    • Astinenza sessuale (nessun rapporto sessuale)
    • Dispositivo intrauterino (IUD) o sistema intrauterino (IUS)
    • Legatura bilaterale delle tube (entrambe le tube legate)
    • Partner vasectomizzato
    7. I pazienti di sesso maschile devono essere disposti a utilizzare la contraccezione di barriera durante l'intero periodo di trattamento in studio e fino a 4 mesi dopo l'ultima dose del farmaco in studio, o astenersi completamente da rapporti eterosessuali
    E.4Principal exclusion criteria
    1) Off target mechanisms of actions, such as mutations or amplification of other genes, changes of histology, etc.
    2) Lab assessments as follows:
    a. Absolute neutrophil count <1.5 × 109/L.
    b. Platelet count <100 × 109/L.
    c. Hemoglobin <9 g/dL (transfusion is acceptable to meet this criterion).
    d. Serum creatinine =1.5 × institutional upper limit of normality (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate can also be used in place of creatinine or CrCl) <50 mL/min for subjects with creatinine levels >1.5 × institutional ULN).
    e. Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase =2.5 × ULN. Subjects with 1) bone metastases and 2) no hepatic parenchymal metastases on screening radiographic examinations may enroll if the alkaline phosphatase is <5 × ULN. Subjects with hepatic parenchymal metastases on screening radiographic examinations may enroll if the aspartate aminotransferase and alanine aminotransferase are >2.5 × ULN only with medical monitor approval.
    f. Total bilirubin =1.5 × ULN.
    g. International normalized ratio or prothrombin time (PT) >1.5 × ULN.
    h. Activated partial thromboplastin time (aPTT) >1.5 × ULN.
    3) Anticancer medications or investigational drugs within the following ranges:
    a. <14 days for chemotherapy, targeted small-molecule therapy or radiation therapy;
    b. <28 days or 5-half-lives (whichever is longer) before first dose of investigational combination therapy.
    4) Subjects with previous grade 3 or 4 adverse event to anti-EGFR treatment, even if the toxicity is related only to laboratory anomalies and the subjects are asymptomatic
    5) History or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis
    6) Subjects who have not recovered adequately from toxicity and/or complications from surgical intervention prior to starting therapy.
    8) Evidence or history of interstitial lung disease or active non-infectious pneumonitis.
    9) Concomitant medication with strong inhibitors or inducers of CYP2C8 and CYP3A4.
    10) Known active CNS metastases. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks before the first dose of study treatment and no need of changes to corticosteroids dose for the management of neurologic symptoms).
    11) Significant, uncontrolled, or active cardiovascular disease, specifically including
    12) Major surgery within 30 days of the first dose of brigatinib. Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.
    13) Another primary malignancy other than NSCLC, except for adequately treated nonmelanoma skin cancer or cervical cancer in situ; definitively treated nonmetastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
    14) Symptomatic brain metastasis (parenchymal or leptomeningeal). Patients with asymptomatic brain metastasis or who have stable symptoms that did not require an increased dose of corticosteroids to control symptoms in the past 7 days before the first dose of brigatinib may be enrolled.
    15) Current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression are allowed
    16) Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
    17) Subject has a known history of or is positive for hepatitis B (HBsAg reactive or HBV DNA detected) or hepatitis C (HCV antibody positive and/or HCV RNA is detected).
    18) Known history of human immunodeficiency virus (HIV).
    19) Active infection requiring systemic therapy.
    20) Pregnancy or lactating female;
    21) Other serious illness or medical condition potentially interfering with the study.
    1. Meccanismi di azione off target, come mutazioni o amplificazione di altri geni, cambiamenti dell'istologia, ecc.
    2. Valutazioni di laboratorio come segue:
    a) Conta assoluta dei neutrofili <1.5 × 109/L.
    b) Conta piastrinica <100 × 109/L.
    c) Emoglobina <9 g/dL (la trasfusione è accettabile se soddisfa questo criterio).
    d) Creatinina sierica =1.5 il limite superiore di normalità istituzionale (ULN) OPPURE clearance della creatinina misurata o calcolata (la velocità di filtrazione glomurulare può essere utilizzata anche al posto della creatinina o CrCl) <50 mL/min per soggetti con livelli di creatinina >1.5 l’ULN istituzionale.
    e) Aspartato aminotransferasi, alanina aminotransferasi e fosfatasi alcalina >2.5 l’ULN. I soggetti con 1) metastasi ossee e 2) metastasi non al parenchima epatico agli esami radiografici dello screening possono essere arruolati se la fosfatasi alcalina è <5 l’ULN. I soggetti con metastasi al parenchima epatico agli esami radiografici dello screening possono essere arruolati se l’aspartato aminotransferasi e l’alanina aminotransferasi sono >2.5 l’ULN solo in seguito all’approvazione del medical monitor.
    f) Bilirubina totale =1.5 l’ULN.
    g) L’INR o tempo di protrombina (PT) >1.5 l’ULN.
    h) Tempo di tromboplastina parziale attivata (aPTT) >1.5 l’ULN.
    3. Farmaci antitumorali o farmaci sperimentali nei seguenti intervalli:
    a) <14 giorni per chemioterapia, terapia mirata con piccole molecole o radioterapia.
    b) <28 giorni o 5 emivite (a seconda di quale sia più lunga) prima della prima dose della terapia combinata sperimentale.
    4. Soggetti con precedente evento avverso di grado 3 o 4 al trattamento anti-EGFR, anche se la tossicità è correlata solo ad anomalie di laboratorio e il soggetto è asintomatico.
    5. Storia o presenza al basale di malattia interstiziale polmonare, polmonite correlata al farmaco o polmonite da radiazioni.
    6. Soggetti che non si sono ripresi adeguatamente dalla tossicità e/o dalle complicanze dell'intervento chirurgico prima dell'inizio della terapia.
    7. Evidenza o storia di malattia polmonare interstiziale o polmonite non infettiva attiva.
    8. Farmaci concomitanti con potenti inibitori o induttori di CYP2C8 e CYP3A4.
    9. Evidenza di metastasi attive del SNC.
    10. Malattia cardiovascolare significativa, incontrollata o attiva,
    11. Intervento chirurgico maggiore entro 30 giorni dalla prima dose di brigatinib. Sono consentite procedure chirurgiche minori come il posizionamento del catetere o biopsie minimamente invasive.
    12. Un'altra neoplasia primaria diversa dal NSCLC, ad eccezione del cancro della pelle non melanoma adeguatamente trattato o del cancro cervicale in situ; carcinoma prostatico non metastatico trattato definitivamente; o pazienti con un altro tumore maligno primario che sono definitivamente liberi da recidiva con almeno 3 anni trascorsi dalla diagnosi dell'altro tumore primario.
    13. Metastasi sintomatiche del SNC (parenchimali o leptomeningee). Possono essere arruolati pazienti con metastasi asintomatiche del SNC o che hanno sintomi stabili che non hanno richiesto un aumento della dose di corticosteroidi per controllare i sintomi negli ultimi 7 giorni prima della prima dose di brigatinib.
    14. Attuale compressione del midollo spinale (sintomatica o asintomatica e rilevata mediante imaging radiografico). Sono ammessi pazienti con malattia leptomeningea e senza compressione del midollo.
    15. Incapacità di deglutire il cibo o qualsiasi condizione del tratto gastrointestinale superiore che precluda la somministrazione di farmaci per via orale.
    16. Storia nota di epatite B o positività al test dell’epatite B (HBsAg reattivo o HBV DNA rilevato) o dell’epatite C (anticorpo HCV positivo e/o HCV RNA rilevato).
    17. Storia nota di HIV.
    18. Infezione attiva che richiede una terapia sistemica.
    19. Donne in gravidanza o in allattamento.
    20. Altre gravi malattie o condizioni mediche che potenzialmente interferiscono con lo studio.
    E.5 End points
    E.5.1Primary end point(s)
    · Phase 1: Safety and tolerability will be assessed by monitoring the frequency, duration, and severity of adverse events (AEs) through physical examination, changes in vital signs and ECGs, and through clinical laboratory blood and urine sample evaluations.
    · Phase 2: Objective response rate, defined as the percentage of subjects having a complete response (CR) or partial response (PR), will be determined by investigator assessment of radiographic disease as per RECIST v1.1.
    Endpoints primari
    Fase 1: La sicurezza e la tollerabilità saranno valutate monitorando la frequenza, la durata e la severità degli eventi avversi (EA) attraverso l'esame obiettivo, i cambiamenti nei segni vitali, negli ECG e attraverso valutazioni cliniche di laboratorio delle analisi del sangue e dei campioni di urina.
    Fase 2: Il tasso di risposta obiettiva (ORR), definito come la percentuale di pazienti che hanno una risposta completa (CR) o una risposta parziale (PR), sarà valutato dallo sperimentatore mediante imaging in accordo ai criteri RECIST 1.1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Phase 1: Continuous - at each medical examination of the patient

    Phase 2 : Continuous -every 8 weeks ± 7 days for the first 12 months and then every 12 weeks ± 7 days
    Fase 1: continuativo - ad ogni visita medica del paziente
    Fase 2: continuativo - ogni 8 settimane ± 7 giorni nei primi 12 mesi e poi ogni 12 settimane ±7 giorni
    E.5.2Secondary end point(s)
    · Phase 1: Objective response rate, defined as the percentage of subjects having a complete response (CR) or partial response (PR), will be determined by investigator assessment of radiographic disease as per RECIST v1.1
    · Phase 2: Safety and tolerability will be assessed by monitoring the frequency, duration, and severity of adverse events (AEs), through physical examinations, changes in vital signs and ECGs, and through clinical laboratory blood and urine sample evaluations
    · Phase 2: Progression-free survival, defined as the time from date of first dose of study drug until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1, or death due to any cause, if occurring sooner than progression.
    Endpoints secondari
    Fase 1: Il tasso di risposta obiettiva (ORR), definito come la percentuale di pazienti che hanno una risposta completa (CR) o una risposta parziale (PR), sarà valutato dallo sperimentatore mediante imaging in accordo ai criteri RECIST 1.1.
    Fase 2: La sicurezza e la tollerabilità saranno valutate monitorando la frequenza, la durata e la severità degli eventi avversi (EA) attraverso l'esame obiettivo, i cambiamenti nei segni vitali, negli ECG e attraverso valutazioni cliniche di laboratorio delle analisi del sangue e dei campioni di urina.
    Fase 2: Sopravvivenza libera da progressione, definita come il tempo dalla data della prima dose del farmaco in studio fino alla prima data di progressione della malattia, come valutato dallo sperimentatore mediante imaging in accordo ai criteri RECIST 1.1, o morte per qualsiasi causa, se si verifica prima della progressione.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Phase 1: Continuous -every 8 weeks ± 7 days for the first 12 months and then every 12 weeks ± 7 days


    Phase 2 : Continuous - at each medical examination of the patient
    Phase 2: Continuous -every 8 weeks ± 7 days for the first 12 months and then every 12 weeks ± 7 days
    Fase 1: continuativo - ogni 8 settimane ± 7 giorni nei primi 12 mesi e poi ogni 12 settimane ±7 giorni

    Fase 2: continuativo - ad ogni visita medica del paziente
    Fase 2: : continuativo - ogni 8 settimane ± 7 giorni nei primi 12 mesi e poi ogni 12 settimane ±7 giorni
    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 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) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    to test the safety and tolerability of the association of brigatinib and cetuximab
    testare la sicurezza e la tollerabilità dell'associazione di brigatinib e cetuximab
    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 No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    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 years2
    E.8.9.1In the Member State concerned months6
    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 months6
    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: 32
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 16
    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 state48
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 48
    F.4.2.2In the whole clinical trial 48
    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)
    If a patient discontinues treatment prior to radiologic progression, then the patient should still continue to be followed until confirmed objective disease progression.
    Following confirmed progression, patients should continue to be followed up for survival every 3 months (12 weeks) till 2 years from last patient first visit
    SAEs must be collected and reported during the study and for up to 100 days after the last dose of study medication
    Se un paziente interrompe il trattamento prima della progressione radiologica, allora il paziente deve continuare ad essere seguito fino alla conferma della progressione obiettiva della malattia.
    Dopo la progressione confermata, i pazienti devono continuare a essere seguiti per la sopravvivenza ogni 3 mesi (12 settimane) fino a 2 anni dalla prima visita dell'ultimo paziente.
    I SAE devono essere raccolti e riportati durante lo studio e fino a 100 giorni dopo l'ultima dose del farmaco in studio
    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 Decision2021-08-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-03-23
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2023-05-05
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA