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    Summary
    EudraCT Number:2022-000391-19
    Sponsor's Protocol Code Number:CAT_AOSPTR001
    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:2022-02-04
    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 number2022-000391-19
    A.3Full title of the trial
    A Single Arm Phase II Study of CAbozantinib in relapsing IDH-1wt, MET amplified Glioblastoma: (“CAT” Study)
    Sperimentazione clinica di fase 2 a singolo braccio con CAbozantinib nel glioblastoma recidivo, IDH-1 non mutato e con meT iperespresso: (Studio "CAT").
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study on Cabozantinib in subjects with recurrent or progressive glioblastoma with c-MET hyperexpression
    Studio su Cabozantinib in pazienti affetti da glioblastoma ricorrente o in progressione con iperespressione di c-MET
    A.3.2Name or abbreviated title of the trial where available
    CAT
    CAT
    A.4.1Sponsor's protocol code numberCAT_AOSPTR001
    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 SponsorAZIENDA OSPEDALIERA "S. MARIA"
    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 supportIPSEN SPA
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAzienda Ospedaliera S. Maria
    B.5.2Functional name of contact pointStudy Coordinator- Clinical Trial O
    B.5.3 Address:
    B.5.3.1Street AddressViale Tristano di Joannuccio
    B.5.3.2Town/ cityTerni
    B.5.3.3Post code05100
    B.5.3.4CountryItaly
    B.5.4Telephone number+390744205631
    B.5.5Fax number+390744205631
    B.5.6E-mailagnese.isori@hotmail.it
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name CABOMETYX - 40 MG- COMPRESSA RIVESTITA CON FILM- USO ORALE- FLACONE (HDPE)- 30 COMPRESSE
    D.2.1.1.2Name of the Marketing Authorisation holderIPSEN PHARMA
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameCabozantinib
    D.3.2Product code [Cabozantinib]
    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 INNCabozantinib
    D.3.9.1CAS number 849217-68-1
    D.3.9.2Current sponsor codeXL184
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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 CABOMETYX - 60 MG- COMPRESSA RIVESTITA CON FILM- USO ORALE- FLACONE (HDPE)- 30 COMPRESSE
    D.2.1.1.2Name of the Marketing Authorisation holderIPSEN PHARMA
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameCabozantinib
    D.3.2Product code [Cabozantinib]
    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 INNCabozantinib
    D.3.9.1CAS number 849217-68-1
    D.3.9.2Current sponsor codeXL184
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    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: 3
    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 CABOMETYX - 20 MG- COMPRESSA RIVESTITA CON FILM- USO ORALE- FLACONE (HDPE)- 30 COMPRESSE
    D.2.1.1.2Name of the Marketing Authorisation holderIPSEN PHARMA
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameCabozantinib
    D.3.2Product code [Cabozantinib]
    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 INNCabozantinib
    D.3.9.1CAS number 849217-68-1
    D.3.9.2Current sponsor codeXL184
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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
    recurrent or progressive glioblastoma with c-MET hyperexpression
    glioblastoma ricorrente o in progressione con iperespressione di c-MET
    E.1.1.1Medical condition in easily understood language
    recurrent or progressive glioblastoma after standard treatment, characterized by hyperexpression of c-MET
    glioblastoma ricorrente o in progressione dopo terapia standard, caratterizzato da iperespressione di c-MET
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10018336
    E.1.2Term Glioblastoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the 6-month progression-free survival (PFS) rate of cabozantinib in patients with recurrent or progressive glioblastoma, with c-MET hyperexpression
    Valutare il tasso di sopravvivenza libera da progressione a 6 mesi di cabozantinib in pazienti con glioblastoma ricorrente o progressivo con iperespressione di c-MET
    E.2.2Secondary objectives of the trial
    1) To evaluate the activity of cabozantinib in term of objective response rate (ORR)
    2) To evaluate the duration of response (DOR).
    3) To evaluate the median overall survival (OS).
    4) To evaluate the 12-month OS rate.
    5) To evaluate the safety of cabozantinib.
    6) To evaluate the reduction of glucocorticoid use during the therapy with cabozantinib.
    1) valutare l'attività di cabozantinib in termini di tasso di risposta oggettiva (ORR)
    2) valutare la durata della risposta (DOR)
    3) valutare la mediana di sopravvivenza (OS)
    4) valutare il tasso globale di sopravvivenza a 12 mesi
    5) valutare la sicurezza di cabozantinib
    6) valutare la riduzione nell'uso di glucocorticoidi durante la terapia con cabozantinib
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    •Male or female cases = 18 years of age.
    •Histologically confirmed WHO grade IV glioma
    •First recurrence or progression of GBM after standard treatment in patients who have not received further therapeutic interventions and that could not be treated with surgery or radiotherapy.
    •Measurable disease by RANO criteria: For patients not undergoing a second surgery at the time of relapse, recurrent disease must include at least one bi-dimensionally measurable contrast-enhancing lesion with clearly defined margins by MRI scan, with minimal diameters of 10 mm, visible on 2 or more axial slices 5 mm apart, based on an MRI scan done within 2 weeks prior to randomization.
    •Documented progression of disease as defined by RANO criteria at least 12 weeks after completion of radiotherapy, unless the recurrence is outside the radiation field or has been histologically documented.
    •Diagnosis of IDH1/2 wild type GBM with any MGMT methylation status
    •Evidence of c-MET hyperexpression
    •Have adequate bone marrow function, liver function, and renal function, as measured by the following laboratory assessments conducted within 7 days prior to the initiation of study treatment:
    - Hemoglobin>9.0 g/dl
    - Absolute neutrophil count (ANC) >1500/mm3 without transfusions or granulocyte colony stimulating factor and other hematopoietic growth factors
    - Platelet count =100,000/µl
    - White blood cell count (WBC) >3.0 x 100/L
    - Total bilirubin <1.5 times the upper limit of normal
    - ALT and AST <3 x upper limit of normal (<5 x upper limit of normal for patients with liver involvement of their cancer and/or have bone metastasis)
    - Serum creatinine <1.5 x upper limit of normal
    - Alkaline phosphatase <2.5 x ULN
    - PT-INR/PTT <1.5 x upper limit of normal (Patients treated with oral anticoagulants or therapeutic dose of heparin will be excluded. Patients treated with heparin for thromboprophylaxis will be allowed to participate).
    - Glomerular filtration rate = 30 mL/min.
    •Understand, be willing to give consent, and sign the written informed consent form (ICF) prior to undergoing any study-specific procedure.
    •Female subjects of childbearing potential must have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment.
    •Sexually active subjects (male and female) must agree to use medically accepted methods of contraception (eg, intrauterine device, oral contraceptive, or double-barrier method) during the course of the study and for 4 months following discontinuation of study drug.
    •Karnofsky performance status (KPS) =70% within 14 days prior to the initiation of study treatment.
    •Stable or decreasing dosage of glucocorticoids during the 7 days prior to the baseline MRI scan.
    • Maschi o femmine di età = 18 anni.
    • Glioma di grado IV confermato istologicamente
    • Recidiva o progressione di GBM dopo trattamento standard in pazienti che non hanno ricevuto ulteriori interventi terapeutici e che non possono essere trattati con chirurgia o radioterapia.
    • Malattia misurabile secondo i criteri RANO: per i pazienti che non si sottopongono ad un secondo intervento chirurgico al momento della ricaduta, la malattia ricorrente deve includere almeno una lesione misurabile bidimensionalmente
    • Progressione della malattia documentata come definita dai criteri RANO almeno 12 settimane dopo il completamento della radioterapia, a meno che la recidiva non sia al di fuori del campo di irradiazione o sia stata documentata istologicamente.
    • Diagnosi di GBM IDH1 / 2 wt con qualsiasi stato di metilazione MGMT
    • Evidenza di iperespressione di c-MET
    • Adeguata funzionalità midollare, epatica e renale, misurata alle valutazioni di laboratorio condotte non oltre 7 giorni prima dell'inizio del trattamento in studio:
    - Emoglobina> 9,0 g / dl senza trasfusioni e fattori di crescita ematopoietici
    - Conta assoluta dei neutrofili (ANC)> 1500 / mm3 senza fattore stimolante le colonie di granulociti
    - Conta piastrinica =100.000 / µl
    - Conta dei globuli bianchi (WBC)> 3,0 x 100 / L
    - Bilirubina totale <1,5 volte il limite superiore della norma
    - ALT e AST <3 volte il limite superiore della norma
    - Creatinina sierica <1,5 volte il limite superiore della norma
    - Fosfatasi alcalina <2,5 x ULN
    - PT-INR / PTT <1,5 x limite superiore normale (Saranno esclusi i pazienti trattati con anticoagulanti orali o dose terapeutica di eparina. Saranno ammessi i pazienti trattati con eparina per tromboprofilassi).
    - Filtrato glomerulare = 30 mL / min.
    • Comprendere, essere disposti a dare il consenso e firmare il modulo di consenso informato scritto (ICF) prima di sottoporsi a qualsiasi procedura specifica per lo studio.
    • I soggetti di sesso femminile in età fertile devono avere un risultato negativo in un test di gravidanza eseguito un massimo di 7 giorni prima dell'inizio del trattamento in studio.
    • I soggetti sessualmente attivi (maschi e femmine) devono accettare di utilizzare metodi contraccettivi accettati (ad es. Dispositivo intrauterino, contraccettivo orale o metodo a doppia barriera) durante il corso dello studio e per 4 mesi dopo l'interruzione del farmaco in studio
    • Karnofsky performance status (KPS) =70% entro 14 giorni prima dell'inizio del trattamento in studio.
    • Dosaggio stabile o decrescente di glucocorticoidi durante i 7 giorni precedenti la scansione MRI di base.
    E.4Principal exclusion criteria
    •Diagnosis of IDH1/2-mutated GBM.
    •Previous non-standard dose of radiation therapy for glioblastoma.
    •Radiotherapy within 12 weeks prior to the diagnosis of progression, if the lesion is in the radiation field.
    •Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, hormonal therapy and other investigational therapy (including agents not specified above) within 28 days prior to the first scheduled dose of cabozantinib.
    •Prior anti-angiogenic therapy (small-molecule kinase inhibitors including bevacizumab and cabozantinib) at any time.
    •Prior treatment with carmustine wafer.
    •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment.
    •Inability to swallow oral tablets (crushing of study treatment tablets is not allowed).
    •Current therapy with warfarin (or other coumarin derivatives) at study entry and not indication to switch to low molecular weight heparin.
    •Evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin may enter the study.
    •Any conditions that contraindicate MRI scan (eg, has pacemaker).
    •The subject has received enzyme-inducing anti-epileptic agents within 2 weeks before the first dose of cabozantinib (eg, carbamazepine, phenytoin, phenobarbital, primidone).
    •The subject has not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade = 1 from adverse events (AEs) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered before study enrolment.
    •Evidence of wound dehiscence from recent surgery.
    •Pregnancy or breast-feeding.
    •Serious intercurrent illness, such as uncontrolled hypertension (systolic blood pressure [SBP] > 140 mmHg or diastolic blood pressure [DBP] > 90 mmHg) despite optimal medical management, cardiac arrhythmias or a recent history of significant disease such as either symptomatic congestive heart failure classified as New York Heart Association Class 2 or higher, unstable angina pectoris within the past 3 months, myocardial infarction within the past 6 months, arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within 6 months prior to the initiation of study treatment or active infection requiring systemic treatment/hospitalization within 2 weeks of the first scheduled dose of cabozantinib.
    •Renal failure requiring hemodialysis or peritoneal dialysis.
    •Inherited bleeding diathesis or coagulopathy with the risk of bleeding.
    •Hemorrhage or a bleeding event = Grade 3 (NCI-CTCAE v 4.0) within 4 weeks prior to the initiation of study treatment.
    •Any live virus vaccine received within 28 days or any inactivated vaccine within 7 days prior to first dose of cabozantinib.
    •Other active malignancy (unless nonmelanoma skincancer, in situ carcinoma of the cervix, or a malignancy diagnosed = 5 years previously).
    •Known allergy or hypersensitivity to any of the components of the cabozantinib formulations.
    •Any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results.
    •Any malabsorption condition.
    • Diagnosi di GBM mutato in IDH1 / 2.
    • Precedente dose non standard di radioterapia per il glioblastoma.
    • Radioterapia entro 12 settimane prima della diagnosi di progressione, se la lesione in progressione è nel campo di irradiazione.
    • Terapia antitumorale sistemica inclusa terapia citotossica, inibitori della trasduzione del segnale, immunoterapia, terapia ormonale e altra terapia sperimentale (inclusi agenti non specificati sopra) entro 28 giorni prima della prima dose programmata di cabozantinib.
    • Precedente terapia anti-angiogenica
    • Procedura chirurgica maggiore, biopsia aperta o lesione traumatica significativa nei 28 giorni prima dell'inizio del trattamento in studio.
    • Incapacità di deglutire le compresse orali (non è consentito frantumare le compresse del trattamento in studio).
    • Terapia con warfarin (o altri derivati cumarinici) e non indicazione a passare all'eparina a basso peso molecolare.
    • Evidenza di emorragia intracranica o intratumorale acuta riscontrata mediante risonanza magnetica o tomografia computerizzata (TC). Possono entrare nello studio soggetti con alterazioni emorragiche in via di risoluzione, emorragia puntata o emosiderina.
    • Qualsiasi condizione che controindica la risonanza magnetica (ad esempio, pacemaker).
    • Il soggetto ha ricevuto agenti antiepilettici induttori enzimatici nelle 2 settimane prima della prima dose di cabozantinib (ad es. carbamazepina, fenitoina, fenobarbital, primidone).
    • Il soggetto non ha raggiunto il grado = 1 secondo i Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 del National Cancer Institute per quel che riguarda gli eventi avversi legati all’intervento chirurgico, agenti antineoplastici, farmaci sperimentali o altri farmaci somministrati prima dell'arruolamento nello studio
    • Deiscenza della ferita di interventi chirurgici recenti.
    • Gravidanza o allattamento.
    • Malattia intercorrente grave, come ipertensione non controllata (pressione sanguigna sistolica > 140 mmHg o pressione sanguigna diastolica > 90 mmHg) nonostante una gestione medica ottimale, aritmie cardiache o una storia recente di malattia significativa come il scompenso cardiaco congestizio sintomatico classificato come New York Heart Association Classe 2 o superiore, angina pectoris instabile negli ultimi 3 mesi, infarto del miocardio negli ultimi 6 mesi, eventi trombotici arteriosi o embolici come accidenti cerebrovascolari (inclusi attacchi ischemici transitori) o embolia polmonare entro 6 mesi prima dell'inizio del trattamento in studio o infezione attiva che richiede trattamento sistemico / ospedalizzazione nelle 2 settimane precedenti la prima dose programmata di cabozantinib.
    • Insufficienza renale che richiede emodialisi o dialisi peritoneale.
    • Diatesi emorragica ereditaria o coagulopatia con rischio di sanguinamento.
    • Emorragia o evento di sanguinamento = Grado 3 (NCI-CTCAE v 4.0) entro 4 settimane prima dell'inizio del trattamento in studio.
    • Qualsiasi vaccino a virus vivo ricevuto nei 28 giorni o qualsiasi vaccino inattivato nei 7 giorni prima della prima dose di cabozantinib.
    • Altre neoplasie attive (a meno che non sia un carcinoma cutaneo diverso dal melanoma, un carcinoma in situ della cervice o un tumore maligno diagnosticato = 5 anni prima).
    • Nota allergia o ipersensibilità ad uno dei componenti della formulazione di cabozantinib.
    • Qualsiasi altra malattia grave o instabile, o condizione medica, psicologica o sociale, che potrebbe compromettere la sicurezza del soggetto e / o il suo rispetto delle procedure di studio, o potrebbe interferire con la partecipazione del soggetto allo studio o alla valutazione del risultati dello studio.
    • Qualsiasi condizione di malassorbimento
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the 6-month progression-free survival (PFS) rate.
    L'endpoint primario è il tasso di sopravvivenza libera da progressione (PFS) a 6 mesi.
    E.5.1.1Timepoint(s) of evaluation of this end point
    6 months
    6 mesi
    E.5.2Secondary end point(s)
    Number of patients with a 50% reduction in total daily corticosteroid dose compared with baseline, or reduction of the total daily dose to =2 mg of dexamethasone (or equivalent dose of other corticosteroid).; safety analysis of cabozantinib based on subjects who experienced toxicities as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 criteria, including serious adverse events (SAEs) and events of clinical interest (ECIs). The attribution to drug, time-of-onset, duration of the event, its resolution, and any concomitant medications administered will be recorded.; Objective Response Rate (ORR) measured as proportion of patients with PR or CR, using criteria of the modified Response Assessment in Neuro-Oncology (modified RANO) as assessed by an independent radiology facility (IRF).; Duration Of Response (DOR); 12-month overall survival rate; median Overall Survival (mOS)
    Numero di pazienti con una riduzione del 50% nell'uso di corticosteroidi in confronto con il baseline, o riduzione della dose totale =2 mg di desametasone ( o dose equivalente di altri corticosteroidi); Analisi di sicurezza di cabozantinib basata sui soggetti con tossicità secondo NCI CTCAE, versione 5, inclusi SAE e ECIs. Saranno riportati l'attribuzione di causalità, il tempo di insorgenza, la durata dell'evento e i farmaci concomitanti.; Tasso di risposta obiettiva (ORR), misurata come proporzione di pazienti con CR o PR, utilizzando i criteri della valutazione della risposta modificata in neuro-oncologia (RANO modificato) valutata da una struttura di radiologia indipendente (IRF),; Durata della risposta (DOR); Tasso di sopravvivenza globale a 12 mesi; Sopravvivenza globale mediana (mOS)
    E.5.2.1Timepoint(s) of evaluation of this end point
    During therapy with cabozantinib; AEs will be recorded up from informed consent to 30-days from the last dose. Subjects with an AE of Grade > 1 and SAEs will be followed until the resolution of the AE to Grade 0 - 1 or until the beginning of a new anti-cancer therapy, whichever occurs first.; At partial or complete response (PR or CR); Time from tumor response to disease progression; 12 months; Time from study entry and data of death. The survival time of living patients will be censored at last date on which the patient is known to be alive or lost to follow-up.
    Durante la terapia con cabozantinib; Tutti gli AEs saranno registati dalla firma del consenso informato fino a 30 giorni dall'ultima dose. AE di grado >1 e SAE saranno seguiti fino a risoluzione, o fino ad inizio di nuova terapia anti-tumorale, quale dei due avvenga prima.; A risposta parziale o completa (PR o CR); Tempo tra risposta tumorale e progressione di malattia; 12 mesi; Tempo tra entrata in studio e data di decesso. Il tempo di sopravvivenza dei pazienti in vita sarà misurato all'ultima data in cui il paziente risulta essere in vita o in cui è perso al 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 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) 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 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 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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    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 years1
    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: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 40
    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)
    Subjects will be treated till desease progression or death or unaccetable adverse events. In case, the PI will discuss with the patient eventual therapy options
    I soggetti saranno trattati fino a progressione della malattia o morte o eventi avversi inaccettabili. Se del caso, il medico discuterà col paziente eventuali opzioni disponibili
    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 Decision2022-04-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-02-23
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2023-10-24
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