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    Summary
    EudraCT Number:2015-000269-30
    Sponsor's Protocol Code Number:MO29518
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-06-17
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2015-000269-30
    A.3Full title of the trial
    AN OPEN-LABEL, MULTICOHORT, PHASE II STUDY OF MPDL3280A IN
    ADVANCED SOLID TUMORS
    STUDIO IN APERTO, MULTI-COORTE, DI FASE II PER LA VALUTAZIONE DI MPDL3280A NEI TUMORI SOLIDI IN STADIO AVANZATO
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An open-label, multicohort, phase II study of MPDL3280A in advanced solid
    tumors
    STUDIO IN APERTO, MULTI-COORTE, DI FASE II PER LA VALUTAZIONE DI MPDL3280A NEI TUMORI SOLIDI IN STADIO AVANZATO
    A.3.2Name or abbreviated title of the trial where available
    BASKET
    BASKET
    A.4.1Sponsor's protocol code numberMO29518
    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 SponsorF. HOFFMANN - LA ROCHE LTD.
    B.1.3.4CountrySwitzerland
    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 supportF. HOFFMANN-LA ROCHE LTD.
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGenentech Inc. c/o F. Hoffmann La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number000000
    B.5.5Fax number000000
    B.5.6E-mailglobal.rochegenentechtrials@roche.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 nameAtezolizumab
    D.3.2Product code [RO5541267-F03-01]
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAtezolizumab
    D.3.9.2Current sponsor codeRO5541267
    D.3.9.4EV Substance CodeSUB126162
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 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 Yes
    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 Tecentriq
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH - EU/1/17/1220/001
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameATEZOLIZUMAB
    D.3.2Product code [RO5541267]
    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 INNATEZOLIZUMAB
    D.3.9.2Current sponsor codeRO5541267
    D.3.9.4EV Substance CodeSUB126162
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 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 Yes
    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 histologically documented advanced solid tumors that
    meet protocol-defined cohort specifications, have progressed following
    at least one line of prior systemic anticancer therapy, or for which there is no alternative therapy known to prolong survival.
    Pazienti affetti da tumori solidi documentati istologicamente che soddisfino una delle specifiche di coorte, che hanno ricevuto almeno una linea di teerapia precedente o per i quali non esista una terapia alternativa nota per prolungare la sopravvivenza.
    E.1.1.1Medical condition in easily understood language
    Patients with several pre-specified types of solid tumors that are progressing after previous therapy, or with no alternative treatment that has demonstrated to prolong survival.
    Paz.con diversi tipi pre-specificati di tumori solidi che hanno progredito dopo la prec. terapia, oppure per i quali non esiste un trattamento alternativo noto per prolungare la sopravv.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10066474
    E.1.2Term Thyroid cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10008229
    E.1.2Term Cervical 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 LLT
    E.1.2Classification code 10004655
    E.1.2Term Biliary carcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10071114
    E.1.2Term Metastatic gastric adenocarcinoma
    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 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 10061306
    E.1.2Term Nasopharyngeal cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10061184
    E.1.2Term Germ cell cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10072737
    E.1.2Term Advanced breast 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 10062042
    E.1.2Term Lung neoplasm
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10055108
    E.1.2Term Thymic cancer metastatic
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10041823
    E.1.2Term Squamous cell carcinoma
    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 10006187
    E.1.2Term Breast 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 10008593
    E.1.2Term Cholangiocarcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10061451
    E.1.2Term Colorectal 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 HLGT
    E.1.2Classification code 10027412
    E.1.2Term Mesotheliomas
    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 10043670
    E.1.2Term Thymoma
    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 10039491
    E.1.2Term Sarcoma
    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 20.1
    E.1.2Level PT
    E.1.2Classification code 10062878
    E.1.2Term Gastrooesophageal cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10049280
    E.1.2Term Solid tumour
    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 main objective is to evaluate the percentage of patients that do not
    experience progression during the first 18 weeks of treatment with MPDL3280A in patients affected by advanced solid tumors.
    L'obiettivo primario di efficacia dello studio ¿ la valutazione del tasso di non progressione (non-progression rate, NPR) a 18 settimane in pazienti affetti da tumori solidi in stadio avanzato, trattati con MPDL3280A, definito come percentuale di pazienti con risposta completa (complete response, CR), risposta parziale (partial response, PR) o malattia stabile (stable disease, SD) secondo il giudizio dello sperimentatore in base alla versione 1.1 dei criteri di valutazione della risposta nei tumori solidi (Response Evaluation Criteria In Solid Tumors, RECIST v1.1)
    E.2.2Secondary objectives of the trial
    The secondary objectives are to evaluate the percentage of patients that do not progress during the first 24 weeks of treatment with MPDL3280A, the percentage of patients that achieve an objective response, the best response
    achieved, the duration of response; the clinical benefit rate, the progression free survival and time to
    progression [all these variables will be evaluated according to both RECIST v1.1 and modified RECIST (latter also NPR at 18 weeks), or disease-specific criteria for prostate cancer and malignant pleural mesothelioma], and overall survival.
    Gli obiettivi secondari sono la valutazione della percentuale di pazienti che non progrediscono durante le prime 24 settimane di trattamento con MPDL3280A, la percentuale di pazienti che raggiungono una risposta globale, la migliore risposta ottenuta, la durata della risposta; il tasso di beneficio clinico, la sopravvivenza libera da progressione e il tempo necessario alla progressione del tumore [tutte queste variabili saranno valutate secondo i criteri RECIST v1.1 e RECIST modificati (ultimo NPR a 18 settimane), o criteri malattia-specifici per il cancro della prostata e il mesotelioma pleurico maligno] e la sopravvivenza complessiva.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Ability to comply with protocol
    2.Male or female, 18 years of age or older
    3.Histologically documented advanced (i.e. stages III or IV) solid tumors that meet protocol-defined cohort specifications, with progressive disease at study entry and at least one prior line of systemic
    anticancer therapy or for which there is no alternative therapy known to prolong survival.
    4.Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in
    paraffin blocks or, in exceptional cases, 15 unstained slides, with an
    associated pathology report, for central testing. Detection of tumor in
    the provided block needs to be confirmed by the central pathology
    laboratory prior to study enrollment. Patients with fewer than 15
    unstained slides available at baseline (but no fewer than 10) may be
    eligible following discussion with the Sponsor. Only tissue from core needle, punch or excisional biopsy sample
    collection will be accepted. For core-needle biopsy specimens, at least
    three cores should be submitted for evaluation. Fine-needle aspiration,
    brushing, bone tissue, and lavage samples are not acceptable
    Patients who do not have tissue specimens meeting eligibility
    requirements must undergo a biopsy during the screening period.
    Acceptable samples include core needle biopsies for deep tumor tissue
    (minimum three cores) or excisional, incisional, punch, or forceps
    biopsies for cutaneous, subcutaneous, or mucosal lesions
    5.Measurable disease as defined by RECIST, v1.1. (except for prostate
    cancer and malignant pleural mesothelioma) or disease-specific criteria
    for patients with prostate cancer (see Appendix 6) and malignant pleural
    mesothelioma (see Appendix 7)
    6.Eastern Cooperative Oncology group ECOG Performance Status of 0 or 1
    7.Adequate hematologic and end organ function, defined by the
    following laboratory results obtained within 14 days prior to the first
    study treatment (Cycle 1, Day 1):
    -Absolute neutrophil count (ANC) = 1500 cells/µL (without granulocyte
    colony-stimulating factor support within 2 weeks before Cycle 1, Day 1)
    -Lymphocyte count = 500/µL
    -White blood cell counts > 2500/µL
    -Platelet count = 100,000/µL (without transfusion within 2 weeks before
    Cycle 1, Day 1)
    -Hemoglobin = 9.0 g/dL (patients may be transfused or receive
    erythropoyetic treatment to meet this criterion)
    -Serum bilirubin < 1.5 × upper limit of normal (ULN), with the following
    exception:
    Patients with known Gilbert disease who have serum bilirubin level = 3
    × ULN may be enrolled
    -Serum albumin level >3.2 g/dl
    -Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and
    alkaline phosphatase = 2.5 × ULN, with the following exceptions:
    Patients with liver involvement: AST and/or ALT = 5 × ULN
    Patients with liver or bone metastases: alkaline phosphatase = 5 × ULN
    -Serum creatinine = 1.5 × ULN or creatinine clearance = 30 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation
    -International normalized ratio (INR) and activated partial
    thromboplastin time (aPTT) = 1.5 × ULN. This applies only to patients
    who do not receive therapeutic anticoagulation; patients receiving
    therapeutic anticoagulation (such as low-molecular weight heparin or
    warfarin) should be on a stable dose
    8.Women who are not postmenopausal (= 12 months of non-therapyinduced
    amenorrhea) or surgically sterile must have a negative serum
    pregnancy test result within 14 days prior to initiation of study drug
    9.For female patients of childbearing potential and male patients with partners of childbearing potential, please refer to the protocol
    1. ICF firmato.
    2. Cap. di rispettare il prot.
    3. Paz. di entrambi i sessi, di età pari o superiore a 18 anni.
    4. Tum. solidi docum. istolog. in stadio avanzato (p.e. stadi III e IV) e che sodd. una delle specifiche di coorte, che hanno mostrato progr. di malattia all’entrata dello studio e che hanno ricevuto almeno una linea di terapia precedente o per i quali non esista una terapia alternativa nota per prolungare la sopravvivenza.
    5. Dispon. di campioni tum. rappresentativi fissati in formalina e inclusi in blocchetti di paraffina (FFPE) (preferiti) o, in casi eccezionali, 15 vetrini in bianco, con associato referto patologico, per la valutazione centralizzata. La presenza di tessuto tumorale presente nei blocchetti (o vetrini) forniti deve essere confermata dal laboratorio centralizzato di patologia prima dell’arruolamento del paziente nello studio. I pazienti con meno di 15 vetrini in bianco disponibili al basale (ma non meno di 10) potrebbero essere idonei previa approvazione dello Sponsor. - Saranno accettabili solo campioni di tessuto prelevati mediante biopsia con ago, con perforatore o escissionale. In caso di agobiopsie devono essere disponibili per la valutazione almeno tre campioni. Non sono accettabili campioni provenienti da agoaspirato, raschiamento, tessuto osseo e lavaggio.
    - I pazienti che non dispongono di campioni di tessuto che soddisfano i requisiti di idoneità dovranno essere sottoposti a biopsia durante il periodo di screening. I campioni accettabili comprendono agobiopsie per il tessuto tum. prof. (min. tre camp.) o biopsie escissionali, incisionali, con perforatore o con forcipe per le lesioni cutanee, sottocutanee o delle mucose.
    6. Malattia misurabile in base ai criteri RECIST v 1.1 (fatta eccezione per il ca. prostatico e il mesotelioma pleurico maligno) oopure ai criteri specifici della malattia per i pazienti affetti da carcinoma prostatico (v. App. 6) e da mesotelioma pleurico maligno (v. App.7).
    7. Perf. status secondo l'ECOG di 0 o 1.
    8. Funzionalità ematol. e d'organo adeguata, definita dai seguenti risultati di lab. ottenuti nei 14 giorni precedenti al primo tratt. dello studio (Giorno 1 del Ciclo 1):
    - ANC = 1500 cellule/µl (senza impiego del fattore di stimolazione della colonia granulocitica nelle 2 settimane precedenti al Giorno 1 del Ciclo 1)
    - Conta linfocitaria = 500/µl
    - Conta leucocitaria > 2500/µl
    - Conta piastrinica = 100.000/µl (senza trasfusioni nelle 2 settimane precedenti al Giorno 1 del Ciclo 1)
    - Hb = 9,0 g/dl (i pazienti possono essere sottoposti a trasfusione o a trattamento eritropoietico per soddisfare questo criterio)
    - Bilirubina sierica < 1,5 volte il limite superiore della norma (ULN), con la seguente eccezione:
    I pazienti con sindrome di Gilbert accertata, con livelli di bilirubina sierica = 3 volte l'ULN possono essere arruolati.
    -Livelli si siero albumina >3.2 g/dl
    - AST, ALT e fosfatasi alcalina = 2,5 volte l'ULN, con le seguenti eccezioni:
    Pazienti con coinvolgimento epatico: AST e/o ALT = 5 volte l'ULN.
    Pazienti con metastasi epatiche o ossee: fosfatasi alcalina = 5 volte l'ULN.
    E.4Principal exclusion criteria
    1.Malignancies other than disease under study within 5 years prior to Cycle 1 Day 1, with the exception of those with a negligible risk of metastasis or death
    2.Uncontrolled tumor-related pain
    3.Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
    4.Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
    5.History of treated asymptomatic or symptomatic CNS metastasis or presence of CNS metastases as determined by CT scan or MRI evaluation during screening or at prior radiographic assessments
    6.Leptomeningeal disease
    7. Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated but not clinically stable for = 2 weeks prior to Cycle 1, Day 1
    8.Any approved anticancer therapy, including chemotherapy, hormonal therapy or radiotherapy, within 3 weeks prior to initiation of study treatment, with certain exceptions
    9.Acute toxicities from previous therapy that have not resolved to Grade = 1, except for alopecia
    10.Pregnant and lactating women
    11.Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease
    12.Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complication
    13.Significant cardiovascular disease within 3 months prior to Cycle 1,Day 1
    14.Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
    15.Severe infections within 4 weeks prior to Cycle 1, Day 1
    16.Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day
    17.Active tuberculosis
    18. Positive test for HIV
    19.Patients with a positive hepatitis B surface antigen [HBsAg] test at screening or hepatitis C
    20.anticipation of need for a major surgical procedure during the course of the study
    21.History of autoimmune disease, except treated/stable autoimmune hypothyroidism or controlled type 1 diabetes mellitus on a stable insulin
    regimen. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are permitted provided
    that they meet certain pre-specified conditions
    22.History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    23.Prior allogeneic bone marrow transplantation or prior solid organ transplantation
    24.History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan
    25.Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study treatment or within 5 months after the last dose of atezolizumab
    26.Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD1, or anti-PDL1 therapeutic antibodies
    27.Treatment with systemic immunostimulatory agents or with an investigational agent within 4 weeks or five half-lives of the drug prior to Cycle 1, Day 1
    28.Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1,or anticipated requirement for systemic immunosuppressive medications during the trial
    1.Malattie tumorali diverse dalle patologie in studio nei 5 anni precedenti alla randomizzazione, fatta eccezione per quelle con un rischio trascurabile di metastasi o decesso
    2.Dolore correlato al tumore e non controllato
    3.Casi non controllati di versamento pleurico, versamento pericardico o ascite che necessitano procedure di drenaggio ricorrenti
    4.Ipercalcemia non controllata o ipercalcemia sintomatica che necessita dell'uso continuato di terapia a base di bifosfonati o denosumab
    5.Storia di metastasi asintomatiche o sintomatiche trattate a carico del SNC o presenza di metastasi a carico del SNC individuate mediante TAC o RM durante lo screening o in precedenti valutazioni radiografiche
    6. Malattia leptomeningea.
    7.Compressione del midollo spinale non trattata in modo definitivo con intervento chirurgico e/o radioterapia o compressione del midollo spinale diagnosticata e trattata in precedenza senza evidenza di malattia clinicamente stabile per = 2 settimane prima del Giorno 1 del Ciclo 1
    8.Tossicità acute dovute a una terapia precedente, che non si sono risolte al grado = 1, fatta eccezione per l'alopecia
    10. Donne in gravidanza e in fase di allattamento al seno
    11.Evidenza di malattia concomitante significativa non controllata, che potrebbe interferire con il rispetto del protocollo o l'interpretazione dei risultati, compresa epatopatia significativa
    12.Qualunque altra malattia, disfunzione metabolica, risultato della visita medica o delle analisi cliniche di laboratorio che inducano il ragionevole sospetto della presenza di una malattia o condizione che costituisca una controindicazione all'impiego di un farmaco sperimentale, che possa influire sull’interpretazione dei risultati o che determini per il paziente un elevato rischio di complicazioni legate al trattamento
    13.Malattia cardiovascolare significativa prima del Giorno 1 del Ciclo 1
    14.Segni e sintomi di infezione nelle 2 settimane precedenti al Giorno 1 del Ciclo 1
    15.Infezioni gravi nelle 4 settimane precedenti al Giorno 1 del Ciclo 1
    16.Trattamento con antibiotici orali o EV nelle 2 settimane precedenti al Giorno 1 del Ciclo 1
    17.Tubercolosi attiva
    18.Test positivo per l'HIV
    19.Pazienti con forma attiva di epatite B antigene di superficie [HBsAg] allo screening o epatite C
    20.Previsione di necessità di una procedura chirurgica maggiore durante lo svolgimento dello studio
    21.Anamnesi di malattia autoimmune, ad eccezione dell’ipotiroidismo e del diabete mellito di tipo 1 controllato, trattato con un regime insulinico stabile. I pazienti con eczema, psoriasi, lichen simplex chronicus, vitiligine con solo manifestazioni dermatologiche sono permessi confermando che rispettino certi criteri.
    22.Anamnesi di gravi reazioni allergiche o anafilattiche oppure altre reazioni da ipersensibilità ad anticorpi chimerici o umanizzati o alle proteine di fusione
    23.Precedente trapianto allogenico di midollo osseo o precedente trapianto di organo solido
    24.Anamnesi di fibrosi polmonare idiopatica, polmonite indotta da farmaco, polmonite organizzativa o evidenza di polmonite attiva evidenziata con la TAC al torace eseguita allo screening
    25.Somministrazione di un vaccino vivo attenuato nelle 4 settimane precedenti al Giorno 1 del Ciclo 1 o previsione della necessità di somministrazione di tale vaccino vivo attenuato durante lo studio o entro 5 mesi dopo l’ultima dose di Atezolizumab
    26.Trattamento precedente con agonisti di CD137 o terapie che bloccano i punti di controllo immunitari, anticorpi terapeutici anti-PD1 o anti-PD-L1
    27.Trattamento con agenti immunostimolanti sistemici oppure con farmaco sperimentale nelle 4 settimane o nelle cinque emivite del farmaco precedenti al Giorno 1 del Ciclo 1
    28.Trattamento con corticosteroidi sistemici o altri farmaci immunosoppressori sistemici nelle 2 settimane precedenti al Giorno 1 del Ciclo 1 o necessità di farmaci immunosoppressori sistemici durante lo studio


    E.5 End points
    E.5.1Primary end point(s)
    To evaluate non-progression rate (NPR) at 18 weeks in patients with advanced solid tumors treated with Atezolizumab, defined as the percentage of patients with complete response (CR), partial response (PR) or stable disease (SD) as assessed by the Investigator according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) or according to disease-specific criteria for prostate cancer and malignant pleural mesothelioma.
    Valutazione del tasso di non progressione (non-progression rate, NPR) a 18 settimane in pazienti affetti da tumori solidi in stadio avanzato, trattati con MPDL3280A, definito come percentuale di pazienti con risposta completa (complete response, CR), risposta parziale (partial response, PR) o malattia stabile (stable disease, SD) secondo il giudizio dello sperimentatore in base alla versione 1.1 dei criteri di valutazione della risposta nei tumori solidi (Response Evaluation Criteria In Solid Tumors, RECIST v1.1) oppure ad eccezione dei criteri specifici della malattia per i pazienti affetti da carcinoma prostatico e da mesotelioma pleurico maligno.
    E.5.1.1Timepoint(s) of evaluation of this end point
    18 settimane
    18 weeks
    E.5.2Secondary end point(s)
    1. Efficacy: To evaluate NPR at 24 weeks, overall response rate (ORR),best overall response (BOR), clinical benefit rate (CBR), duration of response (DOR), time to tumor progression (TTP) and progression-free survival (PFS), as assessed by the Investigator using RECIST v1.1 and modified RECIST (latter also NPR at 18 weeks) or by disease-specific criteria for prostate cancer and malignant pleural mesothelioma.Overall survival (OS).; 2. Safety: incidence, nature, and severity of adverse events, incidence of anti-atezolizumab antibodies, mean dose and number of cycles of atezolizumab.; 3. Pharmacokinetics: maximum and minimum serum atezolizumab concentrations.
    1. Efficacia: valutazione del NPR a 24 settimane, del tasso di risposta globale (overall response rate, ORR), della risposta globale migliore (best overall response, BOR), del tasso di beneficio clinico (clinical benefit rate, CBR), della durata della risposta (duration of response, DOR), del tempo alla progressione del tumore (time to tumor progression, TTP) e della sopravvivenza libera da progressione (progression-free survival, PFS), secondo il giudizio dello sperimentatore in base ai criteri RECIST v1.1 e ai criteri RECIST modificati (NPR a 18 settimane) oppure ai criteri specifici della malattia per i pazienti affetti da carcinoma prostatico e da mesotelioma pleurico maligno. Verr¿ inoltre valutata la sopravvivenza globale (overall survival, OS).; 2. Sicurezza: incidenza, natura e seriet¿ degli eventi aversi,incidenza degli anticorpi anti-Atezolizumab, dalla dose e dal numero di cicli.; 3. Farmacocinetica: valutazione della concentrazione massima e minima di Atezolizumab.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Efficacy: 18 and 24 weeks (NPR), up to 24 months (OS).; 2. Safety: up to 24 months.; 3. Pharmacokinetics: Cmax at 30 minutes after tend of infusion on Day 1 of Cycle 1; Cmin up to 24 months.
    1. Efficacia: da 18 e 24 settimane (NPR), fino a 24 mesi (OS).; 2.Sicurezza: fino a 24 mesi.; 3. Farmacocinetica: concentrazione massima a 30 minuto a seguito all'infusione al giorno 1 del ciclo 1; concentrazione minima fino a 24 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 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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA32
    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
    Austria
    Brazil
    Canada
    Denmark
    Finland
    France
    Germany
    Ireland
    Italy
    Netherlands
    Norway
    Poland
    Russian Federation
    Spain
    Switzerland
    Turkey
    United Kingdom
    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 study for each cohort will occur when all patients have been
    followed for survival for a minimum of 24 months after the last patient
    has been enrolled or until all patients have died, withdrawn consent or
    are lost to follow up, whichever occurs first.
    La fine dello studio per ogni coorte corrisponder¿ alla data in cui tutti i pazienti saranno stati sottoposti a monitoraggio della sopravvivenza per almeno 24 mesi dopo l'arruolamento dell'ultimo paziente in ciascuna coorte o tutti i pazienti saranno deceduti, avranno ritirato il consenso o saranno persi al follow-up, a seconda di quale evento si verifichi per primo.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months2
    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: 545
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 180
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 580
    F.4.2.2In the whole clinical trial 725
    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)
    The Sponsor will offer post-trial access to the study drug free of charge to eligible patients in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product (http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf).
    Patients may also take part in an extension study if the patient is still benefiting from the treatment.
    Il Promotore valuterà se continuare a fornire i trattamenti in studio dopo la conclusione dello studio principale ai sensi della politica globale di Roche relativa all’accesso continuo ai farmaci sperimentali, disponibile al seguente indirizzo: http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
    I pazienti possono inoltre prendere parte ad uno studio di estensione , se il pazienete sta ancora beneficiando del trattamento.
    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 Decision2015-06-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-04-29
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-07-28
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