E.1 Medical condition or disease under investigation |
E.1.1 | Medical 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. |
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E.1.1.1 | Medical 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. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066474 |
E.1.2 | Term | Thyroid cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008229 |
E.1.2 | Term | Cervical cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004655 |
E.1.2 | Term | Biliary carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071114 |
E.1.2 | Term | Metastatic gastric adenocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061306 |
E.1.2 | Term | Nasopharyngeal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061184 |
E.1.2 | Term | Germ cell cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072737 |
E.1.2 | Term | Advanced breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062042 |
E.1.2 | Term | Lung neoplasm |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055108 |
E.1.2 | Term | Thymic cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041823 |
E.1.2 | Term | Squamous cell carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008593 |
E.1.2 | Term | Cholangiocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10027412 |
E.1.2 | Term | Mesotheliomas |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043670 |
E.1.2 | Term | Thymoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039491 |
E.1.2 | Term | Sarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062878 |
E.1.2 | Term | Gastrooesophageal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049280 |
E.1.2 | Term | Solid tumour |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main 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) |
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E.2.2 | Secondary 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary 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.
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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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary 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. |
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E.5.2.1 | Timepoint(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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Canada |
Russian Federation |
Turkey |
United States |
Austria |
Denmark |
Finland |
France |
Germany |
Ireland |
Italy |
Netherlands |
Norway |
Poland |
Spain |
Switzerland |
United Kingdom |
|
E.8.7 | Trial 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.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |