Study of Atezolizumab as Monotherapy and in Combination With Platinum-Based Chemotherapy in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma

Urothelial Carcinoma Clinical Trial

— IMvigor130  

Official title:

A Phase III, Multicenter, Randomized, Placebo-Controlled Study of Atezolizumab (Anti-PD-L1 Antibody) as Monotherapy and in Combination With Platinum-Based Chemotherapy in Patients With Untreated Locally Advanced or Metastatic Urothelial Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02807636
• Other study ID #: WO30070
• Secondary ID: 2016-000250-35
• Status: Completed
• Phase: Phase 3
• Start date: June 30, 2016
• Est. completion date: February 12, 2024

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase III, randomised study of atezolizumab alone and in combination with chemotherapy versus chemotherapy alone in participants with untreated advanced urothelial cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1213
• Est. completion date: February 12, 2024
• Est. primary completion date: August 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion on Day 1 of each 21-day cycle until investigator-assessed disease progression per RECIST v1.1. In specific circumstances treatment may continue beyond disease progression.
• Carboplatin
Carboplatin will be administered at doses to achieve area under the concentration-time curve (AUC) of 4.5 milligram per milliliter into minute (mg/mL*min) by IV infusion on Day 1 of each 21-day cycle until investigator-assessed disease progression per RECIST v1.1 or unacceptable toxicity.
• Gemcitabine
Gemcitabine will be administered at a dose of 1000 milligrams per square meter (mg/m^2) by IV infusion on Day 1 and Day 8 of each 21-day cycle, until investigator-assessed disease progression per RECIST v1.1 or unacceptable toxicity.

Other:
• Placebo
Placebo matched to atezolizumab will be administered by IV infusion on Day 1 of each 21-day cycle until investigator-assessed disease progression per RECIST v1.1. In specific circumstances treatment may continue beyond disease progression.

Drug:
• Cisplatin
Cisplatin will be administered at a dose of 70 mg/m^2 by IV infusion on Day 1 of each 21-day cycle until investigator-assessed disease progression per RECIST v1.1 or unacceptable toxicity.

Locations

Country	Name	City	State
Australia	Lyell McEwin Hospital	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Ashford Cancer Center Research	Kurralta Park	South Australia
Australia	Macquarie University Hospital	Macquarie Park	New South Wales
Australia	Cabrini Medical Centre; Oncology	Malvern	Victoria
Australia	Sunshine Hospital; Oncology Research	St Albans	Victoria
Belgium	GHdC Site Notre Dame	Charleroi
Belgium	AZ Sint Lucas (Sint Lucas)	Gent
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	CHC MontLégia	Liege
Bosnia and Herzegovina	University Clinical Centre of the Republic of Srpska	Banja Luka
Bosnia and Herzegovina	Clinical center University of Sarajevo	Sarajevo
Brazil	Hospital Luxemburgo; Oncologia	Belo Horizonte	MG
Brazil	Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda	Ijui	RS
Brazil	Clinica de Neoplasias Litoral	Itajai	SC
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Clinicas Oncologicas Integradas - COI	Rio De Janeiro	RJ
Brazil	Clinica Viver	Santa Maria	RS
Brazil	Hospital de Base de Sao Jose do Rio Preto	Sao Jose do Rio Preto	SP
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Brazil	Beneficencia Portuguesa de Sao Paulo	São Paulo	SP
Brazil	CETUS Hospital Dia Oncologia	Uberaba	MG
Canada	Tom Baker Cancer Centre-Calgary; Clinical Research Unit	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Clinic; Clinical Trials Department	Hamilton	Ontario
Canada	BC Cancer Agency, CSI	Kelowna	British Columbia
Canada	Dr. Georges L. Dumont University Hospital Centre	Moncton	New Brunswick
Canada	Lakeridge Health Center; R. S. MacLaughlin Durham Regional Cancer Center	Oshawa	Ontario
Canada	North York General Hospital	Toronto	Ontario
Chile	Bradford Hill Centro de Investigaciones Clinicas	Recoleta
Chile	Fundacion Arturo Lopez Perez	Santiago
Chile	OrlandiOncología	Santiago
Chile	Clinica Alemana	Vitacura
China	Beijing Friendship Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing City
China	Chongqing Cancer Hospital	Chongqing
China	Sun Yat-sen Memorial Hospital	Guangzhou
China	Jiangsu Cancer Hospital	Nanjing City
China	Huadong Hospital Affiliated to Fudan University	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai City
China	The 2nd Hospital of Tianjin Medical University	Tianjin
Czechia	Masarykuv onkologicky ustav	Brno
Czechia	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Czechia	University Hospital Motol; Department of Urology	Praha 5
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	North Estonia Medical Centre Foundation; Oncology Center	Tallinn
Finland	Oulu University Hospital; Oncology	Oulu
Finland	Turku Uni Central Hospital; Oncology Clinics	Turku
Georgia	Chemotherapy and Immunotherapy Clinic Medulla	Tbilisi
Georgia	National Center of Urology	Tbilisi
Georgia	Research institute for Clinical Medicine	Tbilisi
Greece	Alexandras General Hospital of Athens; Oncology Department	Athens
Greece	University Hospital of Patras Medical Oncology	Patras
Hong Kong	Princess Margaret Hospital; Oncology	Hong Kong
Hong Kong	Queen Elizabeth Hospital; Clinical Oncology	Hong Kong
Hong Kong	Queen Mary Hospital; Dept. of Clinical Oncology	Hong Kong
Hong Kong	The Chinese University of Hong Kong; Department of Clinical Oncology	N.t.
Israel	Rambam Health Care Campus; Oncology	Haifa
Italy	Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia	Arezzo	Toscana
Italy	ASST DI CREMONA; Dip. Medicina - S.C. Oncologia	Cremona	Lombardia
Italy	Az. Osp. Uni Ria San Martino; Cliniche Uni Rie Convenzionate U.O. Oncologia Medical	Genova	Liguria
Italy	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2	Milano	Lombardia
Italy	A.O. Universitaria Policlinico Di Modena; Oncologia	Modena	Emilia-Romagna
Italy	Azienda Ospedaliera A. Cardarelli; Dip. Oncopneumoematologico	Napoli	Campania
Italy	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima	Padova	Veneto
Italy	Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche	Roma	Lazio
Italy	Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia	Rozzano	Lombardia
Italy	IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia	San Giovanni Rotondo	Puglia
Italy	Azienda Ospedaliera S. Maria - Terni; Oncologia	Terni	Umbria
Italy	A.O CITTA' DELLA SALUTE E DELLA SCIENZA D. - Presidio San Lazzaro; Oncologia medica 2	Torino	Piemonte
Japan	Nagoya University Hospital	Aichi
Japan	Hirosaki University Hospital	Aomori
Japan	National Hospital Organization Shikoku Cancer Center	Ehime
Japan	Gunma University Hospital	Gunma
Japan	National Hospital Organization Hokkaido Cancer Center	Hokkaido
Japan	University of Tsukuba Hospital	Ibaraki
Japan	Kanazawa University Hospital	Ishikawa
Japan	Kumamoto University Hospital	Kumamoto
Japan	Niigata University Medical & Dental Hospital	Niigata
Japan	Kindai University Hospital	Osaka
Japan	Osaka Metropolitan University Hospital	Osaka
Japan	Keio University Hospital	Tokyo
Japan	The Cancer Institute Hospital, JFCR; Urology	Tokyo
Japan	Toranomon Hospital	Tokyo
Korea, Republic of	Kyungpook National University Medical Center	Daegu
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Malaysia	Hospital Kuala Lumpur; Jabatan Radioterapi dan Onkologi	Kuala Lumpur	FED. Territory OF Kuala Lumpur
Malaysia	University Malaya Medical Centre; Clinical Oncology Unit,	Kuala Lumpur	FED. Territory OF Kuala Lumpur
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	IMSS Hospital General de Zona No. 48 S. Pedro Xalpa; Departamento de Urología	Mexico CITY (federal District)
Mexico	Hospital San Jose; Centro de investigacion y transferencia en salud del Tec de Monterrey	Monterrey, N.L	Nuevo LEON
Mexico	Cancerología	Querétaro	Queretaro
Mexico	Consultorio Médico	Zapopan	Jalisco
Netherlands	Hagaziekenhuis, locatie Leyweg	Den-Haag
Netherlands	Martini Ziekenhuis; Dept of Internal Medicine	Groningen
Netherlands	Zuyderland Medisch Centrum; Internal Diseases	Sittard-Geleen
Netherlands	Isala Klinieken, Sophia	Zwolle
Poland	Bialostockie Centrum Onkologii; Oddzial Onkologii Klinicznej	Bialystok
Poland	Przychodnia Lekarska KOMED, Roman Karaszewski	Konin
Poland	Szpital Uniwersytecki w Krakowie; Oddzial Kliniczny Onkologii i Poradnia Onkologiczna	Kraków
Poland	Woj.Wielospecjalistyczne Centrum Onkologii i Traumatologii; Oddz.Hematologii Pododz.Chemioterapii	Lodz
Poland	Oddzial Chemioterapii Szpitala Klinicznego Nr 1 w Poznaniu	Poznan
Poland	NU-MED Centrum Diagnostyki i Terapii Onkologicznej	Tomaszów Mazowiecki
Poland	Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.	Warszawa
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego; Oddzial Urologii i Onkologii	Wroclaw
Portugal	Hospital de Santa Maria; Servico de Oncologia Medica	Lisboa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Romania	Spitalul Judetean de Urgenta Dr Constantin Opris	Baia Mare
Romania	Institute Of Oncology Bucharest; Medical Oncology	Bucharest
Romania	Oncology Center Sf. Nectarie	Craiova
Russian Federation	ALTAI REGIONAL ONCOLOGICAL CENTER; "Nadezhda" Clinic	Barnaul	Altaj
Russian Federation	Ivanovo Regional Oncology Dispensary	Ivanovo
Russian Federation	Krasnoyarsk Regional Oncology Dispensary n.a. Krizhanovsky; Chemotherapy	Krasnoyarsk	Krasnodar
Russian Federation	Blokhin Cancer Research Center; Urological Dept	Moscow	Moskovskaja Oblast
Russian Federation	P.A. Herzen Oncological Inst. ; Oncology	Moscow	Moskovskaja Oblast
Russian Federation	Russian Scientific Center of Roentgenoradiology	Moscow	Moskovskaja Oblast
Russian Federation	Privolzhsk Regional Medical Center	Nizhny Novgorod	Niznij Novgorod
Russian Federation	SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF	Sankt-peterburg	Sankt Petersburg
Russian Federation	Scientific Research Oncology Institute named after N.N. Petrov; Oncology	St. Petersburg	Sankt Petersburg
Russian Federation	SBEI of HPE ?Bashkir State Medical University? of MoH RF	UFA	Baskortostan
Russian Federation	Sverdlovsk Regional Clinical Hospital 1	Yekaterinburg	Sverdlovsk
Serbia	Clinical Center of Serbia; Clinic of Urology	Belgrade
Serbia	Clinical Centre Nis, Clinic for Oncology	Nis
Serbia	Oncology Institute of Vojvodina	Sremska Kamenica
Singapore	National Cancer Centre; Medical Oncology	Singapore
Singapore	National University Hospital; National University Cancer Institute, Singapore (NCIS)	Singapore
Singapore	Oncocare Cancer Centre; Gleneagles Medical Centre	Singapore
Slovenia	Institute of Oncology Ljubljana	Ljubljana
South Africa	GVI Oncology Outeniqua Unit	George
South Africa	Cancercare	Port Elizabeth
South Africa	Steve Biko Academic Hospital; Oncology	Pretoria
South Africa	Wilgers Oncology Centre	Pretoria
South Africa	Sandton Oncology Medical Group	Sandton
Spain	Complejo Hospitalario Universitario de Albacete; Servicio de Oncologia	Albacete
Spain	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona
Spain	Institutio Catalan De Oncologia	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona
Spain	Hospital de Basurto; Servicio de Oncologia	Bilbao	Vizcaya
Spain	Complejo Asistencial Universitario De Burgos; Servicio de Oncologia	Burgos
Spain	Hospital San Pedro De Alcantara; Servicio de Oncologia	Caceres
Spain	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon de La Plana	Castellon
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Hospital General Universitario de Elche; Servicio de Oncologia	Elche	Alicante
Spain	Hospital Universitario Virgen de las Nieves; Servicio de Oncologia	Granada
Spain	Hospital Juan Ramon Jimenez;Servicio de Oncologia	Huelva
Spain	Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia	Jaen
Spain	Complejo Asistencial Universitario de Leon; Servicio de Oncologia	Leon
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Complejo Hospitalario de Althaia; Servicio de Oncologia	Manresa	Barcelona
Spain	Hospital Universitario Son Espases	Palma De Mallorca	Islas Baleares
Spain	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Sant Andreu de La Barca	Barcelona
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Oncologia	Santander	Cantabria
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hospital Universitario de Toledo	Toledo
Spain	Hospital Universitario la Fe; Servicio de Oncologia	Valencia
Spain	Hospital Alvaro Cunqueiro	Vigo	Pontevedra
Spain	Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia	Zaragoza
Spain	Hospital Universitario Miguel Servet; Servicio de Oncologia Medica	Zaragoza
Taiwan	Chang Gung Medical Foundation - Kaohsiung; Oncology	Kaohisung
Taiwan	China Medical University Hospital; Urology	Taichung
Taiwan	Taichung Veterans General Hospital; Division of Urology	Taichung
Taiwan	National Cheng Kung Uni Hospital; Dept of Hematology and Oncology	Tainan
Taiwan	National Taiwan Uni Hospital; Dept of Oncology	Taipei
Taiwan	Chang Gung Medical Foundation-Linkou, Urinary Oncology	Taoyuan
Thailand	Chulalongkorn Hospital; Medical Oncology	Bangkok
Thailand	Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology	Bangkok
Thailand	Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc	Bangkok
Thailand	Vajira Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital; Department of Medicine	ChiangMai
Turkey	Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology	Adana
Turkey	Ankara Bilkent City Hospital	Ankara
Turkey	Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi	Edirne
Turkey	Bezmi Alem Vakif University Medical School; Oncology	Istanbul
Turkey	Istanbul University Cerrahpa?a-Cerrahpa?a Medical Faculty; Medikal Onkoloji Departmani	Istanbul
Turkey	Goztepe Prof.Dr. Suleyman Yalcin City Hospital; Clinical Oncology	Kadiköy
Turkey	Medikal Park Izmir Hospital	Kar??yaka
Turkey	19 Mayis University Medical Faculty; Medical Oncology Department	Samsun
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara
Ukraine	CI Dnipropetrovsk CMCH #4 MA of MOHU Ch of Oncology and MR	Dnipropetrovsk
Ukraine	Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval Department of Urology #4	Kharkiv	Kharkiv Governorate
Ukraine	Zaporizhzhia Regional Clinic	Zaporizhzhia
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	University College London Hospitals NHS Foundation Trust - University College Hospital	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	The York Hospital	York
United States	University of North Carolina, Lineberger Cancer Ctr	Chapel Hill	North Carolina
United States	The University of Chicago Biological Sciences; Dept. of Medicine, Section of Hematology/Oncology	Chicago	Illinois
United States	Florida Cancer Specialists; Department of Oncology	Fort Myers	Florida
United States	Parkview Research Center	Fort Wayne	Indiana
United States	Sarah Cannon Research Institute / Tennessee Oncology	Germantown	Tennessee
United States	Bon Secours - St. Francis Hospital	Greenville	South Carolina
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Norton Cancer Institute	Louisville	Kentucky
United States	East Jefferson Hematology Oncology; Hematology Oncology-Yenni Pavillion	Metairie	Louisiana
United States	Yale School of Medicine	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai School of Medicine - Tisch Cancer Institute	New York	New York
United States	Christina Care Institutional Review Board	Newark	Delaware
United States	Norwalk Hospital	Norwalk	Connecticut
United States	UF Health Cancer Center at Orlando Health	Orlando	Florida
United States	Park Nicollet Clin-Cancer Ctr	Saint Louis Park	Minnesota
United States	Florida Cancer Specialists (St. Petersburg ? St. Anthony?s Professional Building)	Saint Petersburg	Florida
United States	Coastal Integrative Cancer Care	San Luis Obispo	California
United States	Highlands Oncology Group	Springdale	Arkansas
United States	Moffitt Cancer Center; GME Office	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Bosnia and Herzegovina,  Brazil,  Canada,  Chile,  China,  Czechia,  Estonia,  Finland,  Georgia,  Greece,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Singapore,  Slovenia,  South Africa,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigator Assessed Progression-Free Survival (PFS) in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm	PFS is defined as the time from randomization to the first documented disease progression as determined by the investigator with the use of RECIST v1.1, or death from any cause, whichever occurs first.	Baseline up to first documented disease progression or death, whichever occurs first (up to approximately 35 months)
Primary	Overall Survival (OS) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm	OS is defined as the time from randomization to death due to any cause.	Baseline until death due to any cause (up to approximately 73 months)
Primary	Overall Survival (OS) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm	OS is defined as the time from randomization to death due to any cause.	Baseline until death due to any cause (up to approximately 73 months)
Secondary	Objective Response Rate (ORR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm	Objective response rate (ORR) is defined as the proportion of participants with a confirmed objective response, either complete response (CR) or partial response (PR), observed on two assessments >= 28 days apart per RECIST v1.1, based on investigator assessment. The analysis population for ORR will be all randomized participants with measurable disease at baseline.	Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)
Secondary	Objective Response Rate (ORR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm	Objective response rate (ORR) is defined as the proportion of participants with a confirmed objective response, either complete response (CR) or partial response (PR), observed on two assessments >= 28 days apart per RECIST v1.1, based on investigator assessment. The analysis population for ORR will be all randomized participants with measurable disease at baseline.	Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)
Secondary	Duration of Response (DOR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm	Duration of response (DOR) is defined for participants with an objective response as the time from the first documented objective response to documented disease progression per RECIST v1.1, based on investigator assessment, or death due to any cause, whichever occurs first.	From first documented objective response (CR or PR) to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)
Secondary	Duration of Response (DOR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm	Duration of response (DOR) is defined for participants with an objective response as the time from the first documented objective response to documented disease progression per RECIST v1.1, based on investigator assessment, or death due to any cause, whichever occurs first.	From first documented objective response (CR or PR) to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)
Secondary	IRF-PFS	Independent review facility PFS (IRF-PFS) is defined as the time from randomization to the first documented disease progression as determined by blinded independent central review with use of RECIST v1.1, or death due to any cause, whichever occurs first.	Randomization to first documented disease progression or death from any cause (up to 35 months)
Secondary	OS Event Free Rate Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm	Overall Survival (OS) Event Free Rate at 1 Year.	Year 1
Secondary	OS Event Free Rate in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm	Overall Survival (OS) Event Free Rate at 1 Year.	Year 1
Secondary	PFS Event Free Rate	Progression Free Survival (PFS) Event Free Rate at Year 1	Year 1
Secondary	Time to Deterioration in Global Health Status as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm	Time to deterioration in global health status as measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm.	Up to approximately 73 months
Secondary	Time to Deterioration in Global Health Status as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm	Time to deterioration in global health status as measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 in the Placebo+Chemo Arm versus Atezolizumab Monotherapy Arm.	Up to approximately 73 months
Secondary	Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm	Median time to deterioration in physical function as measured by the QLQ-C30 in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm.	Up to approximately 73 months
Secondary	Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm	Median time to deterioration in physical function as measured by the QLQ-C30 in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm versus Atezolizumab Monotherapy Arm.	Up to approximately 73 months
Secondary	Maximum Atezolizumab Serum Concentration	Maximum atezolizumab serum concentration.	Cycle 1 Day 1
Secondary	Minimum Atezolizumab Serum Concentration	Minimum atezolizumab serum concentration.	Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, Cycle 16 Day 1, Cycle 24 Day 1, Cycle 32 Day 1, Day 120 post dose of last blinded atezolizumab treatment, and study drug early discontinuation
Secondary	Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs)	Percentage of participants with Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs).	Up to approximately 35 months
Secondary	Investigator-Assessed Progression-Free Survival (INV-PFS) in Participants Treated With Atezolizumab Monotherapy Arm Compared With Placebo+Gemcitabine+Carboplatin/Cisplatin Arm	PFS is defined as the time from randomization to the first documented disease progression as determined by the investigator with the use of RECIST v1.1, or death from any cause, whichever occurs first.	Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (assessed at baseline, every 9 weeks for 54 weeks and every 12 weeks thereafter up to 35 months)
Secondary	Percentage of Participants With Adverse Events (AEs) Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0		Baseline up to 90 months