A Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Enzalutamide in Participants With Metastatic Castration-Resistant Prostrate Cancer (mCRPC) After Failure of an Androgen Synthesis Inhibitor And Failure of, Ineligibility For, or Refusal of a Taxane Regimen

NCT ID: NCT03016312

Last Updated: 2024-08-09

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

759 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-10

Study Completion Date

2022-12-20

Brief Summary

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This Phase III, multicenter, randomized, open-label study will evaluate the safety and efficacy of atezolizumab (anti-programmed death-ligand 1 \[anti-PD-L1\] antibody) in combination with enzalutamide compared with enzalutamide alone in participants with mCRPC after failure of an androgen synthesis inhibitor (e.g., abiraterone) and failure of, ineligibility for, or refusal of a taxane regimen. Participants will be randomized to one of the two treatment arms (atezolizumab in combination with enzalutamide, and enzalutamide alone) in a 1:1 ratio (experimental to control arm) in global randomized phase. Participants will receive treatment until investigator-assessed confirmed radiographic disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria or unacceptable toxicity.

Detailed Description

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Conditions

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Prostatic Neoplasms, Castration-Resistant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Atezolizumab + Enzalutamide

Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type DRUG

Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg), intravenous (IV) infusion on Day 1 of each 21-day cycle.

Enzalutamide

Intervention Type DRUG

Enzalutamide capsules will be administered orally at a dose of 160 mg daily.

Enzalutamide

Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).

Group Type ACTIVE_COMPARATOR

Enzalutamide

Intervention Type DRUG

Enzalutamide capsules will be administered orally at a dose of 160 mg daily.

Interventions

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Atezolizumab

Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg), intravenous (IV) infusion on Day 1 of each 21-day cycle.

Intervention Type DRUG

Enzalutamide

Enzalutamide capsules will be administered orally at a dose of 160 mg daily.

Intervention Type DRUG

Other Intervention Names

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Tecentriq® Xtandi®

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy greater than or equal to (\>/=) 3 months
* Histologically confirmed adenocarcinoma of the prostate
* Known castrate-resistant disease with serum testosterone level less than or equal to (\</=) 50 nanograms per deciliter (ng/dL) with prior surgical castration or ongoing androgen deprivation for the duration of the study
* Progressive disease prior to screening by PSA or imaging per PCWG3 criteria during or following the direct prior line of therapy in the setting of medical or surgical castration
* One prior regimen/line of a taxane-containing regimen for mCRPC or refusal or ineligibility of a taxane-containing regimen
* Progression on a prior regimen/line of an androgen synthesis inhibitor for prostate cancer
* Availability of a representative tumor specimen from a site not previously irradiated that is suitable for determination of programmed death-ligand 1 (PD-L1) status via central testing
* Adequate hematologic and end organ function

Exclusion Criteria

* Prior treatment with enzalutamide or any other newer hormonal androgen receptor inhibitor (e.g., apalutamide, ODM-201)
* Treatment with any approved anti-cancer therapy, including chemotherapy, immunotherapy, radiopharmaceutical or hormonal therapy (with the exception of abiraterone), within 4 weeks prior to initiation of study treatment
* Treatment with abiraterone within 2 weeks prior to study treatment
* Structurally unstable bone lesions suggesting impending fracture
* Known or suspected brain metastasis or active leptomeningeal disease
* Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
* Active or history of autoimmune disease or immune deficiency
* Prior allogeneic stem cell or solid organ transplantation
* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Positive human immunodeficiency virus (HIV) test, active tuberculosis, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
* Prior treatment with cluster of differentiation (CD)137 agonists or immune checkpoint blockade therapies, including anti Cytotoxic T Lymphocyte-Associated 4 (CTLA4), anti-programmed death 1 (PD-1), and anti-PD-L1 therapeutic antibodies
* Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to initiation of study treatment
* Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study
* History of seizure or any condition that may predispose to seizure within 12 months prior to study treatment, including history of unexplained loss of consciousness or transient ischemic attack
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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City of Hope Medical Grp Inc.

Duarte, California, United States

Site Status

University of California San Diego

La Jolla, California, United States

Site Status

Kaiser Permanente San Diego - Los Angeles

Los Angeles, California, United States

Site Status

UC Irvine Medical Center

Orange, California, United States

Site Status

Pacific Hematology Oncology Associates

San Francisco, California, United States

Site Status

University of Colorado; Division of Medical Oncology

Aurora, Colorado, United States

Site Status

Yale School of Medicine

New Haven, Connecticut, United States

Site Status

Stamford Hospital; BCC, MOHR

Stamford, Connecticut, United States

Site Status

Lynn Cancer Institute/Boca Raton Regional Hospital

Boca Raton, Florida, United States

Site Status

SCRI Florida Cancer Specialists South

Fort Myers, Florida, United States

Site Status

Miami Cancer Institute of Baptist Health, Inc.

Miami, Florida, United States

Site Status

Florida Cancer Specialist, North Region

St. Petersburg, Florida, United States

Site Status

Investigative Clin Rsch of IN

Indianapolis, Indiana, United States

Site Status

Associates in Oncology/Hematology P.C.

Rockville, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Karmanos Cancer Institute..

Detroit, Michigan, United States

Site Status

Nebraska Cancer Specialists; Oncology Hematology West, PC

Omaha, Nebraska, United States

Site Status

Urology Cancer Center & GU Research Network

Omaha, Nebraska, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

MSKCC at Basking Ridge

Basking Ridge, New Jersey, United States

Site Status

New York Oncology Hematology, P.C.

Albany, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Oncology Hematology Care, Inc.

Cincinnati, Ohio, United States

Site Status

James Cancer Hospital;Solove Research Institute

Columbus, Ohio, United States

Site Status

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Allegheny Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute; Division of Medical Oncology

Pittsburgh, Pennsylvania, United States

Site Status

Miriam Hospital

Providence, Rhode Island, United States

Site Status

Charleston Oncology, P .A

Charleston, South Carolina, United States

Site Status

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Site Status

Sarah Cannon Research Institute / Tennessee Oncology

Chattanooga, Tennessee, United States

Site Status

Texas Oncology Cancer Center

Austin, Texas, United States

Site Status

Texas Oncology - Methodist Dallas Cancer Center

Dallas, Texas, United States

Site Status

Texas Oncology, P.A. - Fort Worth

Fort Worth, Texas, United States

Site Status

Texas Oncology - Memorial City

Houston, Texas, United States

Site Status

Texas Oncology-Tyler

Irving, Texas, United States

Site Status

Virginia Cancer Specialists - Alexandria

Alexandria, Virginia, United States

Site Status

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status

Eastern Health; Cancer Services

Box Hill, New South Wales, Australia

Site Status

Concord Repatriation General Hospital; Concord Cancer Centre

Concord, New South Wales, Australia

Site Status

Macquarie University Hospital

Macquarie Park, New South Wales, Australia

Site Status

Royal Brisbane & Women's Hosp; Cancer Care Serv

Herston, Queensland, Australia

Site Status

Adelaide Cancer Centre

Kurralta Park, South Australia, Australia

Site Status

Monash Medical Centre; Oncology

Clayton, Victoria, Australia

Site Status

LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie

Graz, , Austria

Site Status

Ordensklinikum Linz Elisabethinen; Abteilung für Urologie und Andrologie

Linz, , Austria

Site Status

Medizinische Universität Wien; Universitätsklinik für Urologie

Vienna, , Austria

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Onze Lieve Vrouwziekenhuis Aalst

Aalst, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

CHU Sart-Tilman

Liège, , Belgium

Site Status

Tom Baker Cancer Centre-Calgary

Calgary, Alberta, Canada

Site Status

Kingston General Hospital

Kingston, Ontario, Canada

Site Status

Lakeridge Health Oshawa; Oncology

Oshawa, Ontario, Canada

Site Status

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Site Status

Hopital Charles Lemoyne; Centre Integre de Lutte Contre Le Cancer de La Monteregie

Greenfield Park, Quebec, Canada

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Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Sherbrooke - Hopital Fleurimont

Sherbrooke, Quebec, Canada

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CHU de Québec - Université Laval - Hôtel-Dieu de Québec

Québec, , Canada

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Friendship Hospital, Capital Medical University

Beijing, , China

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Jiangsu Cancer Hospital

Nanjing, , China

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Zhongshan Hospital Fudan University

Shanghai, , China

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Fudan University Shanghai Cancer Center

Shanghai, , China

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Masarykuv onkologicky ustav

Brno, , Czechia

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Fakultni nemocnice u sv. Anny v Brne

Brno, , Czechia

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Thomayerova nemocnice

Praha 4 - Krc, , Czechia

Site Status

Aalborg Universitetshospital; Onkologisk Afdeling

Aalborg, , Denmark

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Herlev Hospital; Afdeling for Kræftbehandling

Herlev, , Denmark

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Odense Universitetshospital, Onkologisk Afdeling R

Odense C, , Denmark

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Institut Sainte-Catherine; Oncologie

Avignon, , France

Site Status

Centre Francois Baclesse; Oncologie

Caen, , France

Site Status

Hopital Louis Pasteur; Medecine B

Colmar, , France

Site Status

Centre Oscar Lambret; Chir Cancerologie General

Lille, , France

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Clinique Chenieux; Oncology

Limoges, , France

Site Status

Hopital Saint Louis, Service D Oncologie Medicale

Paris, , France

Site Status

Hopital d'Instruction des Armees de Begin

Saint-Mandé, , France

Site Status

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, , France

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Institut Gustave Roussy

Villejuif, , France

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Universitätsklinikum Freiburg; Chirurgische Klinik; Abteilung Urologie

Freiburg im Breisgau, , Germany

Site Status

Medizinische Hochschule Hannover; Klinik für Urologie und Onkologische Urologie

Hanover, , Germany

Site Status

Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie

Münster, , Germany

Site Status

Universitätsklinikum Tübingen; Klinik für Urologie

Tübingen, , Germany

Site Status

Urologisches Zentrum Euregio; Würselen, Urologische Praxis am Wasserturm

Würselen, , Germany

Site Status

Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine

Athens, , Greece

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Alexandras Hospital; Dept. of Clin. Therapeutics, Athens Uni School of Medicine

Athens, , Greece

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Athens Medical Center; Dept. of Oncology

Athens, , Greece

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IASO General Hospital of Athens

Athens, , Greece

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Agioi Anargyroi Cancer Hospital; 2Nd Oncology Dept.

Kifissia, , Greece

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University Hospital of Patras Medical Oncology

Pátrai, , Greece

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Papageorgiou General Hospital; Medical Oncology

Thessaloniki, , Greece

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Semmelwies University of Medicine; Urology Dept.

Budapest, , Hungary

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Orszagos Onkologiai Intezet; "C" Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály

Budapest, , Hungary

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Debreceni Egyetem Klinikai Kozpont ; Department of Oncology

Debrecen, , Hungary

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Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica

Bari, Apulia, Italy

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IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia

San Giovanni Rotondo, Apulia, Italy

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ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE; Dipartimento Uro-Ginecologico

Napoli, Campania, Italy

Site Status

A.O. Universitaria Policlinico Di Modena; Oncologia

Modena, Emilia-Romagna, Italy

Site Status

Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica

Rome, Lazio, Italy

Site Status

IRCCS AOU San Martino - IST; Oncologia Medica 1

Genoa, Liguria, Italy

Site Status

A.O. Istituti Ospitalieri - Cremona; S.C. Oncologia

Cremona, Lombardy, Italy

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Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2

Milan, Lombardy, Italy

Site Status

Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche

Milan, Lombardy, Italy

Site Status

Ospedale Area Aretina Nord; U.O.C. Oncologia

Arezzo, Tuscany, Italy

Site Status

IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima

Padua, Veneto, Italy

Site Status

Nagoya City University Hospital

Aichi, , Japan

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National Cancer Center East

Chiba, , Japan

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Toho University Sakura Medical Center

Chiba, , Japan

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Kyushu University Hospital

Fukuoka, , Japan

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National Hospital Organization Hokkaido Cancer Center

Hokkaido, , Japan

Site Status

Yokohama City University Medical Center

Kanagawa, , Japan

Site Status

Kitasato University Hospital

Kanagawa, , Japan

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University Hospital Kyoto Prefectural University of Medicine

Kyoto, , Japan

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Nara Medical University Hospital

Nara, , Japan

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Niigata University Medical & Dental Hospital

Niigata, , Japan

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Kansai Medical University Hospital

Osaka, , Japan

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Toranomon Hospital

Tokyo, , Japan

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The Jikei University Hospital

Tokyo, , Japan

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Nippon Medical School Hospital

Tokyo, , Japan

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Woj. Wielospec. Centrum Onkologii i Traumatologii

?ód?, , Poland

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Medical University of Bialystok; Oncology clinic

Bialystok, , Poland

Site Status

Przychodnia Lekarska KOMED, Roman Karaszewski

Konin, , Poland

Site Status

Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii

Krakow, , Poland

Site Status

SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego

Opole, , Poland

Site Status

Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii

Otwock, , Poland

Site Status

Szpital Sw. Elzbiety - Mokotowskie Centrum Medyczne Sp. z o.o.

Warsaw, , Poland

Site Status

Wojewodzki Szpital; Specjalistyczny ul.

Wroclaw, , Poland

Site Status

Russian Scientific Center of Roentgenoradiology

Moscow, Moscow Oblast, Russia

Site Status

P.A. Herzen Oncological Inst. ; Oncology

Moscow, Moscow Oblast, Russia

Site Status

SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

National Cancer Center

Goyang-si, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Institut Catala d?Oncologia Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Insititut Catala D'Oncologia

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

Sabadell, Barcelona, Spain

Site Status

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, Spain

Site Status

Clinica Universitaria de Navarra; Servicio de Oncologia

Pamplona, Navarre, Spain

Site Status

Hospital Universitari Vall d'Hebron; Oncology

Barcelona, , Spain

Site Status

Hospital Clínic i Provincial; Servicio de Oncología

Barcelona, , Spain

Site Status

Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia

Barcelona, , Spain

Site Status

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Clinico San Carlos; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia

Málaga, , Spain

Site Status

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, , Spain

Site Status

Inselspital Bern; Universitätsklinik für Medizinische Onkologie, Klinische Forschungseinheit

Bern, , Switzerland

Site Status

Kantonsspital St. Gallen; Onkologie/Hämatologie

Sankt Gallen, , Switzerland

Site Status

Taichung Veterans General Hospital; Division of Urology

Taichung, , Taiwan

Site Status

National Taiwan University Hospital, Department of Urology

Taipei, , Taiwan

Site Status

TAIPEI VETERANS GENERAL HOSPITAL, Urology

Taipei, , Taiwan

Site Status

Chang Gung Memorial Hospital-LinKou; Urology

Taoyuan District, , Taiwan

Site Status

Royal Blackburn Hospital

Blackburn, , United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status

Barts and the London NHS Trust.

London, , United Kingdom

Site Status

Sarah Cannon Research Institute

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Royal Marsden Hospital; Institute of Cancer Research

Sutton, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Canada China Czechia Denmark France Germany Greece Hungary Italy Japan Poland Russia South Korea Spain Switzerland Taiwan United Kingdom

References

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Powles T, Yuen KC, Gillessen S, Kadel EE 3rd, Rathkopf D, Matsubara N, Drake CG, Fizazi K, Piulats JM, Wysocki PJ, Buchschacher GL Jr, Alekseev B, Mellado B, Karaszewska B, Doss JF, Rasuo G, Datye A, Mariathasan S, Williams P, Sweeney CJ. Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. Nat Med. 2022 Jan;28(1):144-153. doi: 10.1038/s41591-021-01600-6. Epub 2022 Jan 10.

Reference Type DERIVED
PMID: 35013615 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2016-003092-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CO39385

Identifier Type: -

Identifier Source: org_study_id

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