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    Summary
    EudraCT Number:2009-010319-34
    Sponsor's Protocol Code Number:OSI-906-202
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-03-08
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2009-010319-34
    A.3Full title of the trial
    A Phase 1/2 Study Evaluating Intermittent and Continuous OSI 906 and
    Weekly Paclitaxel in Patients with Recurrent Epithelial Ovarian Cancer
    (and Other Solid Tumors)
    Studio di fase I/II per la valutazione dello schema di trattamento con OSI-906 somministrato in modo intermittente o continuo in combinazione con paclitaxel settimanale in pazienti con tumore epiteliale dell`™ovaio in recidiva (o altri tumori solidi)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial investigating OSI-906 in patients with cancer of the
    surface of the ovary and other solid tumors
    Studio Clinico con OSI-906 in pazienti con tumore dell’ovaio e altri tumori solidi
    A.4.1Sponsor's protocol code numberOSI-906-202
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT00889382
    A.5.4Other Identifiers
    Name:ISN 7487-CL-0202Number:Alternative Sponsor Code
    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 SponsorASTELLAS PHARMA GLOBAL DEVELOPMENT, 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 supportAstellas Pharma Global Development, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstellas Pharma Europe B.V.
    B.5.2Functional name of contact pointAstellas Pharma Service Desk
    B.5.3 Address:
    B.5.3.1Street AddressElisabethhof 19
    B.5.3.2Town/ cityLeiderdorp
    B.5.3.3Post code2353 EW
    B.5.3.4CountryNetherlands
    B.5.4Telephone number31 71 5455878
    B.5.5Fax number31 71 5455224
    B.5.6E-mailcontact@nl.astellas.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 nameOSI-906 25 mg tablet
    D.3.2Product code OSI-906
    D.3.4Pharmaceutical form 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 INNlinsitinib
    D.3.9.1CAS number 867160-71-2
    D.3.9.2Current sponsor codeOSI-906
    D.3.9.3Other descriptive nameASP7487
    D.3.9.4EV Substance CodeNA
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameOSI-906 100 mg tablet
    D.3.2Product code OSI-906
    D.3.4Pharmaceutical form 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 INNlinsitinib
    D.3.9.1CAS number 867160-71-2
    D.3.9.2Current sponsor codeOSI-906
    D.3.9.3Other descriptive nameASP7487
    D.3.9.4EV Substance CodeNA
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin 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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 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 nameOSI-906 150 mg tablet
    D.3.2Product code OSI-906
    D.3.4Pharmaceutical form 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 INNlinsitinib
    D.3.9.1CAS number 867160-71-2
    D.3.9.2Current sponsor codeOSI-906
    D.3.9.3Other descriptive nameASP7487
    D.3.9.4EV Substance CodeNA
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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.2.1.1.1Trade name Paclitaxel 6 mg/ml concentrate for solution for infusion
    D.2.1.1.2Name of the Marketing Authorisation holderHospira UK Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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.3.4Pharmaceutical form Concentrate 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 INNPACLITAXEL
    D.3.9.1CAS number 33069-62-4
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameNA
    D.3.9.4EV Substance CodeSUB09583MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    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 Epithelial Ovarian Cancer and Other Solid Tumors
    tumore epiteliale dell’ovaio in recidiva e altri tumori solidi
    E.1.1.1Medical condition in easily understood language
    Cancer on the surface of the ovary and other solid tumors
    tumore dell’ovaio e altri tumori solidi
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10049280
    E.1.2Term Solid tumour
    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 14.1
    E.1.2Level PT
    E.1.2Classification code 10066697
    E.1.2Term Ovarian cancer recurrent
    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
    The primary phase 2 objective of this study is to determine progression free survival (PFS) evaluated by the investigator of 2 different schedules of OSI-906 (Arm A and B) in combination with weekly paclitaxel as compared with paclitaxel alone (Arm C) in recurrent/refractory ovarian cancer patients.
    L'obiettivo primario della fase 2 di questo studio è: •stabilire la sopravvivenza libera da progressione (PFS), valutata dallo sperimentatore, per 2 diversi regimi di OSI-906 (Braccio A e Braccio B) in associazione con paclitaxel settimanale, rispetto alla monoterapia con paclitaxel (Braccio C), in pazienti con carcinoma ovarico ricorrente/refrattario.
    E.2.2Secondary objectives of the trial
    The secondary phase 2 objectives of this study are to evaluate in parallel for OSI-906 and paclitaxel and paclitaxel alone: - objective response rate (ORR) using RECIST v1.1, CA-125 response rate, duration of response (RECIST v1.1), duration of CA-125 response, and overall survival (OS); - the safety profile of the combination of OSI-906 and paclitaxel; - relevant pharmacodynamic markers involved in related pathways; and - exploratory biomarkers related to treatment outcomes and/or histologic characterization
    Gli obiettivi secondari della fase 2 di questo studio sono le valutazioni, in parallelo per OSI-906 e paclitaxel e per paclitaxel in monoterapia, di quanto segue: •il tasso di risposta obiettiva (ORR) sulla base dei criteri RECIST v1.1, il tasso di risposta al CA-125, la durata della risposta (RECIST v1.1), la durata della risposta al CA-125 e la sopravvivenza globale (OS); •il profilo di sicurezza dell'associazione OSI-906 e paclitaxel; •i marcatori farmacodinamici pertinenti coinvolti nelle vie (pathway) correlate; •i biomarcatori esplorativi legati agli esiti del trattamento e/o la caratterizzazione istologica.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients must meet all of the following inclusion criteria to be eligible for participation in this study. - Histologically or cytologically confirmed epithelial ovarian carcinoma Patients with fallopian or peritoneal cancer will also be eligible. Patients with any solid tumor that may be treated with weekly paclitaxel will be eligible for the phase 1 portion. - For the phase 2 portion, patients must have radiologically-confirmed progressive disease by RECIST v1.1 criteria within 6 months prior to randomization (patients must have measurable disease according to RECIST v1.1). - Age ≥ 18 years. - ECOG PS 0 -1 - Predicted life expectancy ≥ 12 weeks. - Patients may have had prior therapy, providing the following conditions are met: Chemotherapy: Prior chemotherapy must have been completed at least 3 weeks prior to study enrollment (6 weeks for mitomycin C, nitrosoureas or high-dose carboplatin [≥ 600 mg/m²]and 4 weeks for investigational drugs. Patient should have recovered from any drug-related toxicities (with the exception of grade 1 neuropathy and or alopecia). Phase 1: While there is no limit on the number of prior regimens for patients entered into the phase 1 portion, any prior taxane therapy must have been administered on a 3 week schedule. Phase 2: Patients must have received prior chemotherapy, which must have contained a platinum and a taxane at some point. Any prior taxane therapy must have been administered on a 3 week schedule. A maximum of 2 prior chemotherapy regimens are permitted. Patients must be refractory (PD during chemotherapy) or resistant (PD within six months of completing chemotherapy) to their last platinum-containing chemotherapy regimen. Radiation: Patients may have had prior radiation therapy provided they have recovered from the acute, toxic effects of radiotherapy prior to registration/randomization. A minimum of 21 days must have elapsed between the end of radiotherapy and registration/randomization into the study unless the radiation affected less than 25% of bone marrow. Surgery: Previous surgery is permitted provided that adequate wound healing has occurred prior to registration/randomization. - Fasting glucose ≤ 150 mg/dL (8.3 mmol/L). - Adequate hematopoietic, hepatic, and renal function defined as follows: Neutrophil count ≥ 1.5 x 10 ^9 /L and platelet count > = 100 x 10^9/L; Bilirubin ≤ 1.5 x ULN; AST and/or ALT ≤ 2.5 x ULN or < = 5 x ULN if patient has documented liver metastases; and Serum creatinine ≤ 1.5 x ULN. - Patients – (For phase 1 both males and females, for phase 2 females and male partners) – with reproductive potential (ie, menopausal for less than 1 year and not surgically sterilized) must agree to practice effective contraceptive measures (ie, barrier methods that include condom or diaphragm, with spermicide) throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration/randomization. - Patients must provide verbal and written informed consent to participate in the study.
    I pazienti devono soddisfare tutti i seguenti criteri di inclusione per poter partecipare a questo studio.
    - Carcinoma ovarico epiteliale confermato istologicamente o citologicamente I pazienti con tumore di Falloppio o peritoneale saranno anche ammissibili. I pazienti con un tumore solido che possono essere trattati con paclitaxel settimanale avranno diritto per la parte di fase 1.
    - Per la parte fase 2, i pazienti devono avere progressione della malattia confermata radiologicamente secondo i criteri RECIST criteri v1.1 nei 6 mesi prima la randomizzazione (i pazienti devono avere malattia misurabile secondo RECIST v1.1).
    - Età ≥ 18 anni.
    - ECOG PS 0 -1
    - Aspettativa di vita ≥ 12 settimane.
    - I pazienti possono aver avuto una precedente terapia, fornendo le seguenti condizioni: Chemioterapia: la chemioterapia preventiva deve essere completata almeno 3 settimane prima dell'arruolamento nello studio (6 settimane per la mitomicina C, nitrosouree o alte dosi di carboplatino [≥ 600 mg / m²] e 4 settimane per farmaci sperimentali.Qualsiasi tossicità da farmaci deve essere risolta (con l'eccezione di grado 1 e neuropatia o alopecia) Fase 1: non vi è alcun limite al numero di precedenti terapie per i pazienti inseriti nella fase 1 qualsiasi terapia precedente con taxani deve essere somministrata a intervalli di 3 settimane Fase 2:i pazienti devono avere ricevuto una precedente chemioterapia che deve aver contenuto platino e un taxano. Qualsiasi terapia precedente con taxani deve essere stato somministrata ogni 3 settimane. Sono ammessi un massimo di 2 precedenti regimi chemioterapici. I pazienti devono essere refrattari (PD durante la chemioterapia) o resistenti (PD entro sei mesi dalla conclusione chemioterapia) al loro ultimo regime chemioterapicon con platino.
    Radioterapia: I pazienti possono aver ricevuto radioterapia a condizione che abbiano recuperato da effetti tossici della radioterapia prima della registrazione / randomizzazione. Devono essere trascorsi almeno 21 giorni tra la fine della radioterapia e la registrazione / randomizzazione a meno che la radiazione abbia colpito meno del 25% di midollo osseo
    Chirurgia: precedente intervento chirurgico è consentito purché ci sia adeguata cicatrizzazione verificata prima della registrazione / randomizzazione
    - Valore glicemia a digiuno ≤ 150 mg / dl (8,3 mmol / L)
    - adeguati valori emopoietici, epatici e renali definiti come segue.: conta dei neutrofili ≥ 1,5 x 10 ^ 9 / L e conta piastrinica &gt; = 100 x 10 ^ 9 / L; bilirubina ≤ 1,5 x ULN,
    AST e / o ALT ≤ 2,5 x ULN o &lt;= 5 x ULN se il paziente ha metastasi al fegato documentata; e creatinina sierica ≤ 1,5 x ULN
    - Pazienti - (Per la fase 1 maschi e femmine, per la fase 2 femmine e partner di sesso maschile) – potenzialmente riproduttivi (in menopausa da meno di 1 anno e non rese sterili chirurgicamente) devono essere d'accordo di pratica misure contraccettive efficaci (ad esempio, metodi di barriera che includono preservativo o diaframma, con spermicida) nel corso dello studio donne in età fertile devono fornire un test di gravidanza negativo (siero o urine) entro 14 giorni prima della registrazione / randomizzazione
    -I pazienti devono fornire consenso informato sia verbale che scritto a partecipare allo studio
    E.4Principal exclusion criteria
    Patients who meet any of the following exclusion criteria are not eligible for enrollment. - Diabetes mellitus currently requiring medication (eg, insulin or oral hypoglycemics). - During the phase 2 portion, patients with histology of abdominal adenocarcinoma of unknown origin or a diagnosis of a borderline ovarian tumor. - Previous or concurrent malignancies (excluding curatively treated basal or squamous cell carcinoma of the skin or cervical carcinoma in situ) unless the patient has been in remission for at least 3 years. - History of significant cardiovascular disease unless the disease is wellcontrolled. Significant cardiac diseases includes second/third degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea). - History of cerebrovascular accident (CVA) within 6 months prior to registration/randomization or that is not stable. - Prior therapy with an IGF1R inhibitor. - Known or prior hypersensitivity to taxanes or drugs containing Cremophor. - Gastro-intestinal abnormalities, including bowel obstruction, inability to take oral medication, requirement for intravenous (IV) alimentation,active peptic ulcer or prior surgical procedures or bowel resection affecting absorption. - Active infection or serious underlying medical condition (including any type of active seizure disorder within 12 months prior to registration/randomization) that would impair the ability of the patient to receive protocol treatment. - History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent. - Pregnancy or breast-feeding. - Symptomatic brain metastases that are not stable, require steroids, are potentially life threatening, or that have required radiation within 28 days prior to registration/randomization. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug. - History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (≥ grade 3), left bundle branch block (LBBB), or asymptomatic sustained ventricular tachycardia are not allowed. Patients with atrial fibrillation controlled by medication are not excluded. Patients with mean QTcF interval ≥ 450 msec at screening are excluded. - Use of drugs that have a known risk of causing Torsade de Pointes (TdP) or that that have a risk of causing QT interval prolongation within 14 days prior to Day 1 dosing are prohibited. - Use of the potent CYP1A2 inhibitors ciprofloxacin and fluvoxamine. Other less potent CYP1A2 inhibitors/inducers are not excluded.
    I pazienti che soddisfano uno dei seguenti criteri di esclusione non sono eleggibili per l'arruolamento.
    - Diabete mellito che richiede trattamento farmacologico (ad esempio insulina o ipoglicemizzanti orali).
    - pazienti con istologia di adenocarcinoma addominale di origine sconosciuta o con una diagnosi di un tumore ovarico borderline.
    - Neoplasie precedenti o concomitanti (ad esclusione carcinoma basocellulare o squamoso della pelle in trattamento o carcinoma cervicale in situ), a meno che il paziente sia in remissione da almeno 3 anni.
    - Storia di significative malattie cardiovascolari a meno che la malattia non sia ben controllata Malattie cardiache significative includono secondo / terzo grado blocco cardiaco; significativa cardiopatia ischemica, ipertensione scarsamente controllata, insufficienza cardiaca congestizia New York Heart Association (NYHA) Classe II o più grave (lieve limitazione dell'attività fisica, bene a riposo, ma l’ordinaria attività fisica si traduce in stanchezza, palpitazioni o dispnea).
    - Storia di AVC cerebrovascolare entro 6 mesi prima della registrazione / randomizzazione o non è stabile.
    - Precedente terapia con un inibitore IGF1R.
    - nota ipersensibilità a farmaci contenenti taxani o Cremophor.
    - Anomalie Gastro-intestinali, compresa occlusione intestinale, incapacità di assumere farmaci per via orale, alimentazione per via endovenosa (IV), ulcera peptica attiva o precedenti procedure chirurgiche o resezione intestinale che influenzano l'assorbimento.
    - Infezione attiva o grave condizione medica (compreso qualsiasi tipo di disturbo convulsivo attivo nei 12 mesi precedenti alla registrazione / randomizzazione) che compromettano la capacità del paziente di ricevere le cure di protocollo.
    - Storia di una condizione psichiatrica che potrebbe compromettere la capacità del paziente di comprendere o di rispettare i requisiti dello studio o di fornire il consenso informato.
    - Gravidanza o allattamento.
    - Metastasi cerebrali sintomatiche che non sono stabili, soggetti che richiedono uso di steroidi, potenzialmente in pericolo di vita, o che hanno richiesto terapia radiante nei 28 giorni prima della registrazione / randomizzazione.
    - Storia di reazioni allergiche riconducibili ai composti di simile origine chimica o composizione biologica al farmaco in studio.
    - Storia di aritmia (Contrazione ventricolare prematuro multifocale, bigeminismo, trigeminismo, tachicardia ventricolare o fibrillazione atriale non controllata) sintomatica o richiede un trattamento (≥ grado 3), blocco di branca sinistra, o asintomatica tachicardia ventricolare sostenuta. I pazienti con fibrillazione atriale controllata con i farmaci non sono esclusi. I pazienti con intervallo medio QTcF ≥ 450 msec allo screening sono esclusi. - Uso di farmaci che hanno un rischio noto di causare torsioni di punta (TdP), o che hanno un rischio di causare prolungamento dell'intervallo QT sono vietati entro i 14 giorni precedenti al giorno 1 dosaggio.
    - Utilizzo del potenti inibitori del CYP1A2 ciprofloxacina e fluvoxamina. Altri induttori meno potenti inibitori del CYP1A2 / non sono esclusi.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy variable is progression free survival (PFS) evaluated by the investigator per RECIST v1.1.
    la variabile primaria di efficacia è la sopravvivenza libera da progressione, valutata dallo sperimentatore per RECIST v1.1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Progression Free Survival (PFS) Time Frame: 36 months
    la sopravvivenza libera da progressione: 36 mesi
    E.5.2Secondary end point(s)
    The second efficacy variables include objective response rate per RECIST v1.1 (ORR), CA- 125 response rate, duration of response (RECIST DOR), duration of CA-125 response (CA-125 DOR), and overall survival (OS).
    Le variabili secondarie di efficacia includono il tasso di risposta obiettiva (sulla base dei criteri RECIST v1.1),il tasso di risposta al CA-125, la durata della risposta (RECIST DOR),la durata della risposta CA-125 (CA-125 DOR) e la sopravvivenza globale(OS)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Objective Response Rate, Cancer Antigen 125 (CA125) Response Rate, Duration of Response, duration of CA-125, Time from the date of the first documented CA-125 response to the date of CA-125 progression, Overall survival, and Safety. Time Frame: 36 months
    Tasso di risposta obiettiva,tasso di risposta al CA-125, durata della risposta, durata di CA.125, tempo dalla data della prima documentata risposta CA-125 alla data di progressione CA-125, sopravvivenza globale e sicurezza. Tempo 36 mesi
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA23
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Russian Federation
    Switzerland
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study will be deemed as the date of the last visit of the last patient participating in the clinical trial. The database may be locked prior to the last visit of the last patient; however, this database lock may not occur until the primary endpoint is reached.
    La conclusione dello studio sarà considerata LPLV.Il database potrà essere chiuso prima LPLV, tuttavia, la chiusura del database non potrà avvenire fino a quando l'endpoint primario non è raggiunto.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months38
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months38
    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.1.1Number of subjects for this age range: 0
    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: 139
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 60
    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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 119
    F.4.2.2In the whole clinical trial 199
    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)
    Standard treatment of care
    terapia standard
    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 Decision2011-12-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-10-05
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-03-01
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