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    Summary
    EudraCT Number:2019-001219-22
    Sponsor's Protocol Code Number:SGNTV-002
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-01-07
    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 number2019-001219-22
    A.3Full title of the trial
    Open Label Phase 2 Study of Tisotumab Vedotin for Patients with Platinum-Resistant Ovarian Cancer with a Safety Run-in of a Dose-Dense Regimen.
    Studio in aperto di Fase 2 su tisotumab vedotin in pazienti affette da carcinoma ovarico platino-resistente con un run-in di sicurezza di un regime dose-dense.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Open Label Phase 2 Study of Tisotumab Vedotin for Patients with Platinum-Resistant Ovarian Cancer with a Safety Run-in of a Dose-Dense Regimen
    Studio in aperto di Fase 2 su tisotumab vedotin in pazienti affette da carcinoma ovarico platino-resistente con un run-in di sicurezza di un regime dose-dense.
    A.3.2Name or abbreviated title of the trial where available
    innovaTV 208
    innovaTV 208
    A.4.1Sponsor's protocol code numberSGNTV-002
    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 SponsorSEATTLE GENETICS, 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 supportGenmab A/S
    B.4.2CountryDenmark
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSeattle Genetics, Inc.
    B.5.2Functional name of contact pointSeagen Clinical Trial Information
    B.5.3 Address:
    B.5.3.1Street Address21823 30th Drive
    B.5.3.2Town/ citySeattle, Bothell, WA
    B.5.3.3Post code98021
    B.5.3.4CountryUnited States
    B.5.4Telephone number0018663337436
    B.5.6E-mailclinicaltrials@seagen.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 nameTisotumab vedotin
    D.3.2Product code [HuMax-TF-ADC]
    D.3.4Pharmaceutical form Powder for 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 INNTISOTUMAB VEDOTIN
    D.3.9.1CAS number 1418731-10-8
    D.3.9.2Current sponsor codeSGD-1006 SG6
    D.3.9.3Other descriptive nameHuMax-TF-ADC
    D.3.9.4EV Substance CodeSUB192227
    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 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 typeAntibody Drug Conjugate (ADC)
    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.2.5The 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 nameALPHAGAN
    D.3.2Product code [ALPHAGAN]
    D.3.4Pharmaceutical form Eye drops, solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOcular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBRIMONIDINA TARTRATO
    D.3.9.2Current sponsor codeALPHAGAN
    D.3.10 Strength
    D.3.10.1Concentration unit % percent
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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.2.5The 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 nameLUXAZONE
    D.3.2Product code [LUXAZONE]
    D.3.4Pharmaceutical form Eye drops, suspension
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOcular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDESAMETASONE
    D.3.9.2Current sponsor codeLuxazone
    D.3.10 Strength
    D.3.10.1Concentration unit % percent
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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: 4
    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.2.5The 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 nameCELLUVISC
    D.3.2Product code [CELLUVISC]
    D.3.4Pharmaceutical form Eye drops, solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOcular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCARMELLOSA SODICA
    D.3.9.2Current sponsor codeCELLUVISC
    D.3.10 Strength
    D.3.10.1Concentration unit mg/l milligram(s)/litre
    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 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
    Patients with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (hereafter collectively referred to as platinum-resistant ovarian cancer and abbreviated as PROC).
    Pazienti affette da carcinoma ovarico epiteliale, carcinoma peritoneale primario o carcinoma delle tube di Falloppio (di seguito collettivamente indicati come carcinoma ovarico platino-resistente e abbreviati con l’acronimo PROC).
    E.1.1.1Medical condition in easily understood language
    Cancer of the ovary.
    Carcinoma dell'ovaio.
    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 10033128
    E.1.2Term Ovarian 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 20.0
    E.1.2Level PT
    E.1.2Classification code 10016180
    E.1.2Term Fallopian tube 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
    (Safety run-in) Evaluate safety and tolerability of a dose-dense regimen of tisotumab vedotin,
    (Parts A and B) Evaluate antitumor activity of tisotumab vedotin.
    (Run-in di sicurezza) Valutare la sicurezza e tollerabilità di un regime dose-dense di tisotumab vedotin,
    (Parti A e B) Valutare l’attività antitumorale di tisotumab vedotin.
    E.2.2Secondary objectives of the trial
    Evaluate the safety and tolerability of tisotumab vedotin,
    Evaluate preliminary antitumor activity of tisotumab vedotin,
    Evaluate antitumor activity of tisotumab vedotin,
    Evaluate durability of response in patients who respond to tisotumab vedotin,
    Evaluate stability and control of disease,
    Evaluate the timing of responses,
    Evaluate progression-free survival (PFS) of patients treated with tisotumab vedotin,
    Evaluate survival of patients treated with tisotumab vedotin,
    Assess pharmacokinetics of tisotumab vedotin,
    Assess immunogenicity of tisotumab vedotin.
    Valutare la sicurezza e tollerabilità di tisotumab vedotin,
    Valutare l’attività antitumorale preliminare di tisotumab vedotin,
    Valutare l’attività antitumorale di tisotumab vedotin,
    Valutare la durata della risposta in pazienti che rispondono a tisotumab vedotin,
    Valutare la stabilità ed il controllo della malattia,
    Valutare il tempo di risposta,
    Valutare la sopravvivenza senza progressione di pazienti trattate con tisotumab vedotin,
    Valutare la sopravvivenza di pazienti trattate con tisotumab vedotin,
    Valutare la farmacocinetica di tisotumab vedotin,
    Valutare l’immunogenicità di tisotumab vedotin.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Histologic documentation of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (excluding carcinosarcoma, mucinous, and low grade serous histologies), hereafter referred to as
    "ovarian cancer".
    2. Safety run-in patients only: Platinum-resistant ovarian cancer (PROC), which is defined as having progressed or relapsed within 6 months after previous platinum-containing chemotherapy and for which single agent chemotherapy is appropriate. Progression or relapse must be documented radiographically using RECIST v1.1 criteria. The patient may have received more than 1 prior systemic treatment regimen in the PROC setting.
    a. Subjects may or may not have received bevacizumab for treatment of ovarian cancer.
    3. Part A and Part B patients only: PROC. The patient must have received at most 1 prior cytotoxic chemotherapy regimen in the PROC setting, and for whom single agent chemotherapy is appropriate as the next line of treatment. Patients eligible to receive a PARP inhibitor may have received such therapy; PARP inhibitors are not considered cytotoxic chemotherapy regimens for the purposes of this study.
    4. Measurable disease according to RECIST v1.1 as assessed by the investigator, defined as:
    a. A minimum of one non-nodal lesion = or >10 mm in the longest diameter from a non-irradiated area. If target lesion(s) are located within previously irradiated area only, the patient can be enrolled only if there has been demonstrated progression in the "in field" lesion and upon approval of the sponsor's medical monitor.
    OR
    b. Lymph node lesion = or >15 mm in the shortest diameter from a nonirradiated area.
    5. Age 18 years or older.
    6. An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 (see Appendix E for conversion of performance status using Karnofsky and Lansky scales, if applicable).
    7. The following baseline laboratory data:
    - Absolute neutrophil count (ANC) = or >1500/µL assessed at least 2 weeks after growth factor support, if applicable.
    - Platelet count = or >100 x 109/L assessed at least 2 weeks after transfusion with blood products.
    - Hemoglobin = or >5.6 mmol/L (9.0 g/dL) assessed at least 2 weeks after transfusion with blood products.
    - Serum bilirubin = or <1.5 x upper limit of normal (ULN) or direct bilirubin = or <2 x ULN in patients diagnosed with Gilbert's syndrome.
    - Estimated glomerular filtration rate (eGFR) = or >50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) study equation as applicable
    - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = or <2.5 x ULN. (If liver tumor/metastases are present, then <5 x ULN is allowed).
    8. Acceptable coagulation status:
    - INR = or <1.2 without anticoagulation therapy.
    - aPTT = or <1.25 ULN.
    9. Life expectancy of at least 3 months.
    10. Patients of childbearing potential as in Section 4.3s:
    - Negative serum or urine pregnancy test result within 7 days prior to the first dose of tisotumab vedotin.
    - Must agree not to breastfeed or donate ova, starting at time of informed consent and continuing through 6 months after the final dose of study drug administration.
    - Must agree to complete abstinence or, if sexually active, must consistently use 2 highly effective methods of birth control starting at time of informed consent and continuing throughout the study and for at least 6 months after the final dose of study drug administration.
    1. Documentazione istologica di carcinoma ovarico epiteliale, carcinoma peritoneale primitivo o carcinoma delle tube di Falloppio (esclusi carcinosarcoma, istologie mucinose e sierose di grado basso), qui di seguito indicato come “carcinoma ovarico”.
    2. Solo per le pazienti nel run-in di sicurezza: Carcinoma ovarico platino-resistente (PROC), definito come progressivo o recidivante entro i 6 mesi successivi la precedente chemioterapia a base di platino e per il quale è adeguata una chemioterapia ad agente singolo. La progressione o la recidiva deve essere documentata a livello radiografico usando i criteri RECIST v1.1. La paziente può aver ricevuto più di 1 precedente regime di trattamento sistemico perPROC.
    3. Solo per le pazienti nella Parte A e Parte B: PROC. La paziente deve essere stata sottoposta al massimo a 1 precedente regime chemioterapico citotossico nel contesto PROC e per la quale una chemioterapia ad agente singolo è appropriata come successiva linea di trattamento. Le pazienti idonee al trattamento con un inibitore della poli ADP-ribosio polimerasi (PARP) possono essere state sottoposte a questa terapia: i PARP-inibitori non sono considerati regimi chemioterapici citotossici ai fini di questo studio.
    a. Se idonee, le pazienti devono essere state sottoposte a precedente trattamento con regime a base di bevacizumab per il carcinoma ovarico. Bevacizumab può essere stato somministrato in precedenza in qualsiasi linea di trattamento.
    4. Malattia misurabile secondo i criteri RECIST v1.1, come da valutazione dello sperimentatore, definita come:
    a. Un minimo di una lesione non nodale = or >10 mm nel diametro più lungo da una zona non irradiata. Se la/e lesione/i bersaglio è/sono localizzata/e solo all’interno della zona precedentemente irradiata, la paziente può essere arruolata solo in presenza di progressione dimostrata nella lesione “in field” e previa approvazione del responsabile del monitoraggio medico dello sponsor.
    OPPURE
    b. Lesione linfonodale = or >15 mm nel diametro più corto da una zona non irradiata.
    5. Età pari o superiore a 18 anni.
    6. Performance statusdel Gruppo Cooperativo Orientale di Oncologia (ECOG) pari a 0 o 1 (vedere Appendice E per la conversione dello stato di validità usando le scale di Karnofsky e Lansky, a seconda del caso).
    7. I seguenti dati di laboratorio al basale:
    - Conta assoluta dei neutrofili (ANC) = or >1500/µL, valutata almeno 2 settimane dopo il supporto al fattore di crescita, se del caso.
    - Conta piastrinica = or >100 x 109/l, valutata almeno 2 settimane dopo la trasfusione con emoderivati.
    - Emoglobina = or >5,6 mmol/l (9,0 g/dl), valutata almeno 2 settimane dopo la trasfusione con emoderivati.
    - Bilirubina sierica = or <1,5 x il limite superiore della normalità (ULN) o bilirubina diretta = or <2 x ULN in pazienti con diagnosi di sindrome di Gilbert.
    - Velocità di filtrazione glomerulare stimata (eGFR) = or >50 ml/min/1,73m2 usando l’equazione dello studio di modifica dell’alimentazione nella malattia renale (MDRD), a seconda del caso.
    - Alanina aminotransferasi (ALT) e aspartato aminotransferasi (AST) = or <2,5 x ULN. (In presenza di tumore/metastasi epatiche, allora è consentito < 5 x ULN).
    8. Stato della coagulazione accettabile:
    - INR = or <1,2 senza terapia anticoagulante.
    - aPTT = or <1,25 ULN.
    9. Aspettativa di vita di almeno 3 mesi.
    10. Pazienti fertili in base alla Sezione 4.3:
    - test di gravidanza su siero o urine negativo nei 7 giorni precedenti la prima dose di tisotumab vedotin.
    - acconsentire a non allattare al seno o donare ovuli a partire dal momento del consenso informato e fino a 6 mesi dopo l’ultima dose del farmaco in studio.
    - acconsentire all’astinenza completa o, se sessualmente attive, usare 2 metodi contraccettivi di elevate efficacia a partire dal momento del consenso informato e fino a 6 mesi dopo l’ultima somministrazione del farmaco in studio.
    E.4Principal exclusion criteria
    1.Primary platinum-refractory disease, defined as disease progression within 2 months of completion of first line platinum-based therapy.
    2. Patients with clinical symptoms or signs of gastrointestinal obstruction within the past 6 months or who currently require parenteral nutrition.
    3.Hematological: Known past or current coagulation defects leading to an increased risk of bleeding; diffuse alveolar hemorrhage from vasculitis; known bleeding diathesis; ongoing major bleeding; trauma
    with increased risk of life-threatening bleeding or history of severe head trauma or intracranial surgery within 8 weeks of trial entry.
    4. Cardiovascular: Clinically significant cardiac disease including uncontrolled hypertension (systolic BP >150 mmHg or diastolic BP >90 mmHg), unstable angina, acute myocardial infarction within 6 months
    prior to screening, serious cardiac arrhythmia requiring medication (not including asymptomatic atrial fibrillation with controlled ventricular rate); any medical history of congestive heart failure (Class II or higher as classified by the New York Heart Association, see Appendix H), or any medical history of decreased cardiac ejection fraction of <45%.
    5. Ophthalmological: Active ocular surface disease at baseline. An ocular evaluation is to be confirmed by an ophthalmologist at screening. Patients with any prior episode of cicatricial conjunctivitis or Stevens Johnson syndrome (as evaluated by the investigator) are ineligible. Cataract is not considered active ocular surface disease for this study.
    6. History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible
    risk of metastasis or death (e.g., 5-year overall survival = or >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, ductal carcinoma in situ, or stage I uterine cancer.
    7. Inflammatory bowel disease including Crohn's disease and ulcerative colitis.
    8. Ongoing, acute, or chronic inflammatory skin disease.
    9. Uncontrolled tumor-related pain.
    10. Inflammatory lung disease, including moderate and severe asthma and chronic obstructive pulmonary disease, requiring chronic medical therapy.
    11. Grade 3 or higher pulmonary disease unrelated to underlying malignancy.
    12. Patients with significant peripheral vascular disease.
    13. Uncontrolled pleural or pericardial effusions.
    1. Malattia primitiva refrattaria al platino, definita come progressione della malattia entro i 2 mesi successivi alla conclusione di una terapia di prima linea a base di platino.
    2. Pazienti con sintomi o segni clinici di occlusione gastrointestinale entro gli ultimi 6 mesi o che al momento richiedono un’alimentazione parenterale.
    3. Aspetti ematologici: Difetti della coagulazione passati o attuali noti con conseguente aumento di rischio di sanguinamenti: emorragia alveolare diffusa da vascolite; diatesi emorragica nota; sanguinamento maggiore in corso; trauma associato a un maggiore rischio di sanguinamento pericoloso per la vita o anamnesi di trauma cranico grave o chirurgia intracranica entro le 8 settimane precedenti all’ingresso nella sperimentazione.
    4. Aspetti cardiovascolari: Malattia cardiaca clinicamente significativa, tra cui ipertensione incontrollata (pressione sanguigna (BP) sistolica > 150 mmHg o BP diastolica > 90 mmHg), angina instabile, infarto miocardico acuto entro i 6 mesi precedenti allo screening, aritmia cardiaca seria che richiede terapia farmacologica (esclusa la fibrillazione atriale asintomatica con frequenza ventricolare controllata); qualsiasi anamnesi medica di insufficienza cardiaca congestizia (di classe II o superiore, secondo la classificazione della New York Heart Association, vedere Appendice H) o qualsiasi anamnesi medica di frazione di eiezione cardiaca ridotta di < 45%.
    5. Aspetti oftalmologici: Malattia della superficie oculare attiva al basale. Una valutazione oculare è da confermare con un oftalmologo allo screening. Le pazienti con precedente episodio di congiuntivite cicatriziale o sindrome di Stevens Johnson (secondo la valutazione dello sperimentatore) non sono idonee. La cataratta non è considerata una malattia della superficie oculare attiva ai fini di questo studio.
    6. Anamnesi di altro tumore maligno nei 3 anni precedenti alla prima dose di farmaco dello studio o qualsiasi evidenza di malattia residua da tumore maligno precedentemente diagnosticato. Fanno eccezione i tumori maligni con rischio trascurabile di metastasi o decesso (per es., sopravvivenza complessiva a 5 anni = or >90%), come ad esempio carcinoma in situ del collo dell’utero adeguatamente trattato, carcinoma cutaneo diverso da melanoma, carcinoma duttale in situ o carcinoma dell’utero allo stadio I.
    7. Malattia intestinale infiammatoria, comprese malattia di Crohn e colite ulcerosa.
    8. Malattia cutanea infiammatoria in corso, acuta o cronica.
    9. Dolore correlato a tumore incontrollato.
    10. Pneumopatia infiammatoria, incluse asma moderata e grave e broncopneumopatia cronica ostruttiva, che richiedono terapia farmacologica cronica.
    11. Pneumopatia di grado 3 o superiore non correlata a tumore maligno preesistente.
    12. Pazienti con malattia vascolare periferica significativa.
    13. Effusioni pleuriche o pericardiche incontrollate.
    E.5 End points
    E.5.1Primary end point(s)
    Incidence of DLTs or other unacceptable toxicities.
    Investigator-determined confirmed ORR as measured by RECIST v1.1.
    Incidenza di DLTs o altre tossicità inaccettabili.
    ORR confermata in base alla valutazione dello sperimentatore e misurata in base ai criteri RECIST v1.1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Safety and tolerability will be assessed at every visit and via phone calls as needed between visits.

    La sicurezza e la tollerabilità saranno valutate ad ogni visita ed attraverso telefonate tra le visite al bisogno.
    E.5.2Secondary end point(s)
    The confirmed and unconfirmed ORR according to RECIST v1.1, CA-125 response rate, combined RECIST/CA-125 overall response rate, and the DCR will be estimated and the 95% CIs will be calculated.
    Saranno stimati l'ORR confermato e non confermato in base ai criteri RECIST v1.1, il tasso di risposta di CA-125, il tasso di risposta complessivo combinato di RECIST/CA-125 ed il DCR e saranno calcolati gli intervalli di confidenza al 95%.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Radiographic tumor assessments.
    Valutazioni radiografiche del tumore.
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA17
    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
    Belgium
    Denmark
    Ireland
    Italy
    Spain
    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 date the patient met criteria for study discontinuation and the reason for study discontinuation will be recorded.
    Saranno registrate la data in cui il paziente soddisfa i criteri di interruzione dello studio e la ragione dell'interruzione dello studio.
    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 years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 82
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    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 state16
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 47
    F.4.2.2In the whole clinical trial 182
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None.
    Nessuno.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-12-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-09-26
    P. End of Trial
    P.End of Trial StatusOngoing
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