Study of Atezolizumab as Monotherapy and in Combination With Platinum-Based Chemotherapy in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma (IMvigor130)
Urothelial Carcinoma
About this trial
This is an interventional treatment trial for Urothelial Carcinoma focused on measuring Urothelial carcinoma, Bladder cancer, Anti-PD-L1, Transitional carcinoma, Tecentriq, Atezolizumab, IMvigor130
Eligibility Criteria
Inclusion Criteria
- Considered to be eligible to receive platinum-based chemotherapy, in the investigator's judgment
- Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (</=) 2
- Histologically documented, locally advanced (T4b, any N; or any T, N2-3) or metastatic urothelial carcinoma (mUC) (M1, Stage IV) (also termed transitional cell carcinoma [TCC] or urothelial cell carcinoma [UCC] of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra)
- Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for central testing and determined to be evaluable for tumor PD-L1 expression prior to study enrollment; participants who have fewer than 15 unstained slides available at baseline (but no less than [<] 10) may be eligible following discussion with the Medical Monitor
- No prior chemotherapy for inoperable locally advanced or mUC
- For participants who received prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a treatment-free interval more than (>) 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment naive in the metastatic setting
- Prior local intravesical chemotherapy or immunotherapy is allowed if completed at least 4 weeks prior to the initiation of study treatment
- Measurable disease, as defined by RECIST v1.1
- Adequate hematologic and end-organ function
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 6 months after the last dose of carboplatin, cisplatin, or gemcitabine or for 5 months after the last dose of atezolizumab
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm
Exclusion Criteria:
- Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
- Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to enrolment
- Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening and prior radiographic assessments
- Participants with treated asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: * Evaluable or measurable disease outside the CNS * No metastases to midbrain, pons, medulla, or within 10 mm of the optic apparatus (optic nerves and chiasm) * No history of intracranial or spinal cord hemorrhage * No ongoing requirement for corticosteroid as therapy for CNS disease; anti-convulsants at a stable dose are allowed * No evidence of significant vasogenic edema * No stereotactic radiation, whole-brain radiation or neurosurgical resection within 4 weeks prior to Cycle 1, Day 1 * Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study * Screening CNS radiographic study >/=4 weeks since completion of radiotherapy or surgical resection and >/=2 weeks since discontinuation of corticosteroids
- Prior treatment with CD137 agonists, anti-CTLA-4, anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents
- Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1 or anticipated requirement for systemic immunosuppressive medications during the study
- Leptomeningeal disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- Uncontrolled tumour-related pain or hypercalcemia
- Significant cardiovascular disease including known left ventricular ejection fraction (LVEF) <40%
- Severe infections within 4 weeks before randomization or therapeutic oral or IV antibiotics within 2 weeks before randomization
- Major surgical procedure within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
- Malignancies other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1
- Life expectancy of <12 weeks
- Pregnant or lactating, or intending to become pregnant during the study
- Serum albumin <25 gram per liter (g/L)
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- History of autoimmune disease
- Participants with prior allogeneic stem cell or solid organ transplantation
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan
- Positive test for human immunodeficiency virus (HIV)
- Active hepatitis B or hepatitis C
- Active tuberculosis
- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
Sites / Locations
- Highlands Oncology Group
- Coastal Integrative Cancer Care
- Yale School of Medicine
- Norwalk Hospital
- Christina Care Institutional Review Board
- Florida Cancer Specialists; Department of Oncology
- UF Health Cancer Center at Orlando Health
- Florida Cancer Specialists (St. Petersburg ? St. Anthony?s Professional Building)
- Moffitt Cancer Center; GME Office
- The University of Chicago Biological Sciences; Dept. of Medicine, Section of Hematology/Oncology
- Parkview Research Center
- Norton Cancer Institute
- East Jefferson Hematology Oncology; Hematology Oncology-Yenni Pavillion
- Park Nicollet Clin-Cancer Ctr
- Comprehensive Cancer Centers of Nevada
- Mount Sinai School of Medicine - Tisch Cancer Institute
- Memorial Sloan Kettering Cancer Center
- University of North Carolina, Lineberger Cancer Ctr
- Bon Secours - St. Francis Hospital
- Sarah Cannon Cancer Center
- Macquarie University Hospital
- Royal Brisbane and Women's Hospital
- Lyell McEwin Hospital
- Ashford Cancer Center Research
- Box Hill Hospital
- Cabrini Medical Centre; Oncology
- Sunshine Hospital; Oncology Research
- GHdC Site Notre Dame
- AZ Sint Lucas (Sint Lucas)
- UZ Leuven Gasthuisberg
- CHC MontLégia
- University Clinical Centre of the Republic of Srpska
- Clinic of Oncology, University Clinical Center Sarajevo
- Hospital Luxemburgo; Oncologia
- CETUS Hospital Dia Oncologia
- Clinicas Oncologicas Integradas - COI
- Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda
- Hospital das Clinicas - UFRGS
- Hospital Sao Lucas - PUCRS
- Hospital Nossa Senhora da Conceicao
- Clinica Viver
- Clinica de Neoplasias Litoral
- Hospital de Base de Sao Jose do Rio Preto
- Instituto do Cancer do Estado de Sao Paulo - ICESP
- Beneficencia Portuguesa de Sao Paulo
- Tom Baker Cancer Centre-Calgary; Clinical Research Unit
- Cross Cancer Institute
- BC Cancer Agency, CSI
- Dr. Georges L. Dumont University Hospital Centre
- Juravinski Cancer Clinic; Clinical Trials Department
- Lakeridge Health Center; R. S. MacLaughlin Durham Regional Cancer Center
- North York General Hospital
- Bradford Hill Centro de Investigaciones Clinicas
- OrlandiOncología
- Fundacion Arturo Lopez Perez
- Clinica Alemana
- Peking Union Medical College Hospital
- Beijing Friendship Hospital
- Chongqing Cancer Hospital
- Sun Yat-sen Memorial Hospital
- Jiangsu Cancer Hospital
- Fudan University Shanghai Cancer Center
- Zhongshan Hospital Fudan University
- Huadong Hospital Affiliated to Fudan University
- The 2nd Hospital of Tianjin Medical University
- Masarykuv onkologicky ustav
- Fakultni nemocnice Olomouc; Onkologicka klinika
- Vseobecna fakultni nemocnice v Praze
- University Hospital Motol; Department of Urology
- East Tallinn Central Hospital
- North Estonia Medical Centre Foundation; Oncology Center
- Oulu University Hospital; Oncology
- Turku Uni Central Hospital; Oncology Clinics
- Research institute for Clinical Medicine
- National Center of Urology
- Chemotherapy and Immunotherapy Clinic Medulla
- Alexandras General Hospital of Athens; Oncology Department
- University Hospital of Patras Medical Oncology
- Princess Margaret Hospital; Oncology
- Queen Elizabeth Hospital; Clinical Oncology
- Queen Mary Hospital; Dept. of Clinical Oncology
- The Chinese University of Hong Kong; Department of Clinical Oncology
- Rambam Health Care Campus; Oncology
- Azienda Ospedaliera A. Cardarelli; Dip. Oncopneumoematologico
- IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
- A.O. Universitaria Policlinico Di Modena; Oncologia
- Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche
- Az. Osp. Uni Ria San Martino; Cliniche Uni Rie Convenzionate U.O. Oncologia Medical
- ASST DI CREMONA; Dip. Medicina - S.C. Oncologia
- Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
- Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
- A.O CITTA' DELLA SALUTE E DELLA SCIENZA D. - Presidio San Lazzaro; Oncologia medica 2
- IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia
- Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia
- Azienda Ospedaliera S. Maria - Terni; Oncologia
- IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima
- Nagoya University Hospital
- Hirosaki University Hospital
- National Hospital Organization Shikoku Cancer Center
- Gunma University Hospital
- National Hospital Organization Hokkaido Cancer Center
- University of Tsukuba Hospital
- Kanazawa University Hospital
- Kumamoto University Hospital
- Niigata University Medical & Dental Hospital
- Osaka Metropolitan University Hospital
- Kindai University Hospital
- Toranomon Hospital
- The Cancer Institute Hospital, JFCR; Urology
- Keio University Hospital
- Kyungpook National University Medical Center
- Gachon University Gil Medical Center
- Severance Hospital, Yonsei University Health System
- Korea University Anam Hospital
- Seoul National University Hospital
- Asan Medical Center
- Samsung Medical Center
- Hospital Kuala Lumpur; Jabatan Radioterapi dan Onkologi
- University Malaya Medical Centre; Clinical Oncology Unit,
- Consultorio Médico
- Health Pharma Professional Research
- Hospital San Jose; Centro de investigacion y transferencia en salud del Tec de Monterrey
- Cancerología
- IMSS Hospital General de Zona No. 48 S. Pedro Xalpa; Departamento de Urología
- Hagaziekenhuis, locatie Leyweg
- Martini Ziekenhuis; Dept of Internal Medicine
- Zuyderland Medisch Centrum; Internal Diseases
- Isala Klinieken, Sophia
- Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej
- Przychodnia Lekarska KOMED, Roman Karaszewski
- Szpital Uniwersytecki w Krakowie; Oddzial Kliniczny Onkologii i Poradnia Onkologiczna
- Woj.Wielospecjalistyczne Centrum Onkologii i Traumatologii; Oddz.Hematologii Pododz.Chemioterapii
- Oddzial Chemioterapii Szpitala Klinicznego Nr 1 w Poznaniu
- NU-MED Centrum Diagnostyki i Terapii Onkologicznej
- Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
- Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego; Oddzial Urologii i Onkologii
- Hospital de Santa Maria; Servico de Oncologia Medica
- IPO do Porto; Servico de Oncologia Medica
- Spitalul Judetean de Urgenta Dr Constantin Opris
- Institute Of Oncology Bucharest; Medical Oncology
- Oncology Center Sf. Nectarie
- ALTAI REGIONAL ONCOLOGICAL CENTER; "Nadezhda" Clinic
- SBEI of HPE ?Bashkir State Medical University? of MoH RF
- Krasnoyarsk Regional Oncology Dispensary n.a. Krizhanovsky; Chemotherapy
- Blokhin Cancer Research Center; Urological Dept
- Russian Scientific Center of Roentgenoradiology
- P.A. Herzen Oncological Inst. ; Oncology
- Privolzhsk Regional Medical Center
- SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF
- Scientific Research Oncology Institute named after N.N. Petrov; Oncology
- Sverdlovsk Regional Clinical Hospital 1
- Ivanovo Regional Oncology Dispensary
- Clinical Center of Serbia; Clinic of Urology
- Clinical Centre Nis, Clinic for Oncology
- Oncology Institute of Vojvodina
- National University Hospital; National University Cancer Institute, Singapore (NCIS)
- National Cancer Centre; Medical Oncology
- Oncocare Cancer Centre; Gleneagles Medical Centre
- Institute of Oncology Ljubljana
- GVI Oncology Outeniqua Unit
- Cancercare
- Wilgers Oncology Centre
- Steve Biko Academic Hospital; Oncology
- Sandton Oncology Medical Group
- Hospital General Universitario de Elche; Servicio de Oncologia
- Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
- Institutio Catalan De Oncologia
- Complejo Hospitalario de Althaia; Servicio de Oncologia
- Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
- Hospital Univ Vall d'Hebron; Servicio de Oncologia
- Hospital Universitario Marques de Valdecilla; Servicio de Oncologia
- Hospital Provincial de Castellon; Servicio de Oncologia
- Hospital Universitario Son Espases
- Clinica Universitaria de Navarra; Servicio de Oncologia
- Hospital Alvaro Cunqueiro
- Hospital de Basurto; Servicio de Oncologia
- Complejo Hospitalario Universitario de Albacete; Servicio de Oncologia
- Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department
- Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
- Complejo Asistencial Universitario De Burgos; Servicio de Oncologia
- Hospital San Pedro De Alcantara; Servicio de Oncologia
- Hospital Universitario Virgen de las Nieves; Servicio de Oncologia
- Hospital Juan Ramon Jimenez;Servicio de Oncologia
- Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia
- Complejo Asistencial Universitario de Leon; Servicio de Oncologia
- Hospital Universitario Lucus Augusti
- Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
- Hospital Ramon y Cajal; Servicio de Oncologia
- Hospital Universitario Clínico San Carlos; Servicio de Oncologia
- Hospital Universitario 12 de Octubre; Servicio de Oncologia
- Hospital Universitario La Paz; Servicio de Oncologia
- Hospital Universitario Virgen del Rocio; Servicio de Oncologia
- Hospital Universitario de Toledo
- Hospital Universitario la Fe; Servicio de Oncologia
- Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia
- Hospital Universitario Miguel Servet; Servicio de Oncologia Medica
- Chang Gung Medical Foundation - Kaohsiung; Oncology
- China Medical University Hospital; Urology
- Taichung Veterans General Hospital; Division of Urology
- National Cheng Kung Uni Hospital; Dept of Hematology and Oncology
- National Taiwan Uni Hospital; Dept of Oncology
- Chang Gung Medical Foundation-Linkou, Urinary Oncology
- Vajira Hospital
- Chulalongkorn Hospital; Medical Oncology
- Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
- Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
- Maharaj Nakorn Chiang Mai Hospital; Department of Medicine
- Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology
- Ankara Bilkent City Hospital
- Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
- Bezmi Alem Vakif University Medical School; Oncology
- Istanbul University Cerrahpa?a-Cerrahpa?a Medical Faculty; Medikal Onkoloji Departmani
- Goztepe Prof.Dr. Suleyman Yalcin City Hospital; Clinical Oncology
- Medikal Park Izmir Hospital
- 19 Mayis University Medical Faculty; Medical Oncology Department
- Hacettepe Uni Medical Faculty Hospital; Oncology Dept
- Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval Department of Urology #4
- CI Dnipropetrovsk CMCH #4 MA of MOHU Ch of Oncology and MR
- Zaporizhzhia Regional Clinic
- Beatson West of Scotland Cancer Centre
- University College London Hospitals NHS Foundation Trust - University College Hospital
- The Christie NHS Foundation Trust
- The York Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Placebo Comparator
Experimental
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin
Placebo+Gemcitabine+Carboplatin/Cisplatin
Atezolizumab Monotherapy
Participants will receive blinded atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin).
Participants will receive blinded placebo matched to atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin).
Eligible participants will receive open-label atezolizumab as monotherapy.