Clinical trial NCT03016312: 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
Official title: A Phase III, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Enzalutamide Versus Enzalutamide Alone in Patients With Metastatic Castration-Resistant Prostate Cancer After Failure of an Androgen Synthesis Inhibitor and Failure of, Ineligibility for, or Refusal of a Taxane Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostatic Neoplasms, Castration-Resistant
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-01-10
Enrollment: 759
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Baseline until death from any cause (up to approximately 42 months)
Secondary outcomes:
measure: Percentage of Participants Who Survived at Month 6 and 12
timeFrame: Months 6, 12
measure: Time to First Symptomatic Skeletal Event (SSE)
timeFrame: Baseline up to end of study (up to approximately 42 months)
measure: Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria
timeFrame: Baseline until disease progression or death from any cause (up to approximately 42 months)
measure: Percentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria
timeFrame: Months 6, 12
measure: Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline
timeFrame: Baseline until disease progression (up to approximately 42 months)
measure: Time to PSA Progression, Assessed as Per PCWG3 Criteria
timeFrame: Baseline until disease progression (up to approximately 42 months)
measure: Percentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria
timeFrame: Baseline until disease progression or death from any cause (up to approximately 42 months)
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to end of study (up to approximately 42 month)
measure: Minimum Observed Serum Concentration (Cmin) of Atezolizumab
timeFrame: Pre-infusion (0 hour[hr]) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); treatment discontinuation visit, 120 days after last dose (up to approximately 42 months)
measure: Maximum Observed Serum Concentration (Cmax) of Atezolizumab
timeFrame: Day Cycle 1 Day 1 0.5 hr post-infusion (infusion duration: 60 minutes [min])
measure: Plasma Concentration of Enzalutamide
timeFrame: Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8
measure: Plasma Concentration of N-Desmethyl Enzalutamide
timeFrame: Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8
measure: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
timeFrame: Predose (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); at atezolizumab discontinuation visit (30 days after last dose); 120 days after last dose of atezolizumab; up to 42 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Grp Inc.
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente San Diego - Los Angeles
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: San Francisco
country: United States
facility: Pacific Hematology Oncology Associates
state: California
city: Aurora
country: United States
facility: University of Colorado; Division of Medical Oncology
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Stamford
country: United States
facility: Stamford Hospital; BCC, MOHR
state: Connecticut
city: Boca Raton
country: United States
facility: Lynn Cancer Institute/Boca Raton Regional Hospital
state: Florida
city: Fort Myers
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute of Baptist Health, Inc.
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialist, North Region
state: Florida
city: Indianapolis
country: United States
facility: Investigative Clin Rsch of IN
state: Indiana
city: Rockville
country: United States
facility: Associates in Oncology/Hematology P.C.
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute..
state: Michigan
city: Omaha
country: United States
facility: Nebraska Cancer Specialists; Oncology Hematology West, PC
state: Nebraska
city: Omaha
country: United States
facility: Urology Cancer Center & GU Research Network
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Basking Ridge
country: United States
facility: MSKCC at Basking Ridge
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Columbus
country: United States
facility: James Cancer Hospital;Solove Research Institute
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute; Division of Medical Oncology
state: Pennsylvania
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Charleston Oncology, P .A
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Chattanooga
country: United States
facility: Sarah Cannon Research Institute / Tennessee Oncology
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Methodist Dallas Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, P.A. - Fort Worth
state: Texas
city: Houston
country: United States
facility: Texas Oncology - Memorial City
state: Texas
city: Irving
country: United States
facility: Texas Oncology-Tyler
state: Texas
city: Alexandria
country: United States
facility: Virginia Cancer Specialists - Alexandria
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Box Hill
country: Australia
facility: Eastern Health; Cancer Services
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital; Concord Cancer Centre
state: New South Wales
city: Macquarie Park
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hosp; Cancer Care Serv
state: Queensland
city: Kurralta Park
country: Australia
facility: Adelaide Cancer Centre
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre; Oncology
state: Victoria
city: Graz
country: Austria
facility: LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie
city: Linz
country: Austria
facility: Ordensklinikum Linz Elisabethinen; Abteilung für Urologie und Andrologie
city: Wien
country: Austria
facility: Medizinische Universität Wien; Universitätsklinik für Urologie
city: Aalst
country: Belgium
facility: Onze Lieve Vrouwziekenhuis Aalst
city: Gent
country: Belgium
facility: UZ Gent
city: Liège
country: Belgium
facility: CHU Sart-Tilman
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre-Calgary
state: Alberta
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa; Oncology
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Greenfield Park
country: Canada
facility: Hopital Charles Lemoyne; Centre Integre de Lutte Contre Le Cancer de La Monteregie
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke - Hopital Fleurimont
state: Quebec
city: Quebec
country: Canada
facility: CHU de Québec - Université Laval - Hôtel-Dieu de Québec
city: Beijing
country: China
facility: Friendship Hospital, Capital Medical University
city: Nanjing City
country: China
facility: Jiangsu Cancer Hospital
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Praha 4 - Krc
country: Czechia
facility: Thomayerova nemocnice
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital; Onkologisk Afdeling
city: Herlev
country: Denmark
facility: Herlev Hospital; Afdeling for Kræftbehandling
city: Odense C
country: Denmark
facility: Odense Universitetshospital, Onkologisk Afdeling R
city: Avignon
country: France
facility: Institut Sainte-Catherine; Oncologie
city: Caen
country: France
facility: Centre Francois Baclesse; Oncologie
city: Colmar
country: France
facility: Hopital Louis Pasteur; Medecine B
city: Lille
country: France
facility: Centre Oscar Lambret; Chir Cancerologie General
city: Limoges
country: France
facility: Clinique Chenieux; Oncology
city: Paris
country: France
facility: Hopital Saint Louis, Service D Oncologie Medicale
city: Saint-Mande
country: France
facility: Hopital d'Instruction des Armees de Begin
city: Toulouse
country: France
facility: Institut Claudius Regaud; Departement Oncologie Medicale
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg; Chirurgische Klinik; Abteilung Urologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover; Klinik für Urologie und Onkologische Urologie
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen; Klinik für Urologie
city: Würselen
country: Germany
facility: Urologisches Zentrum Euregio; Würselen, Urologische Praxis am Wasserturm
city: Athens
country: Greece
facility: Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine
city: Athens
country: Greece
facility: Alexandras Hospital; Dept. of Clin. Therapeutics, Athens Uni School of Medicine
city: Athens
country: Greece
facility: Athens Medical Center; Dept. of Oncology
city: Athens
country: Greece
facility: IASO General Hospital of Athens
city: Kifisia
country: Greece
facility: Agioi Anargyroi Cancer Hospital; 2Nd Oncology Dept.
city: Patras
country: Greece
facility: University Hospital of Patras Medical Oncology
city: Thessaloniki
country: Greece
facility: Papageorgiou General Hospital; Medical Oncology
city: Budapest
country: Hungary
facility: Semmelwies University of Medicine; Urology Dept.
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet; "C" Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont ; Department of Oncology
city: Napoli
country: Italy
facility: ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE; Dipartimento Uro-Ginecologico
state: Campania
city: Modena
country: Italy
facility: A.O. Universitaria Policlinico Di Modena; Oncologia
state: Emilia-Romagna
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica
state: Lazio
city: Genova
country: Italy
facility: IRCCS AOU San Martino - IST; Oncologia Medica 1
state: Liguria
city: Cremona
country: Italy
facility: A.O. Istituti Ospitalieri - Cremona; S.C. Oncologia
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche
state: Lombardia
city: Bari
country: Italy
facility: Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica
state: Puglia
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia
state: Puglia
city: Arezzo
country: Italy
facility: Ospedale Area Aretina Nord; U.O.C. Oncologia
state: Toscana
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima
state: Veneto
city: Aichi
country: Japan
facility: Nagoya City University Hospital
city: Chiba
country: Japan
facility: National Cancer Center East
city: Chiba
country: Japan
facility: Toho University Sakura Medical Center
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hokkaido
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
city: Kanagawa
country: Japan
facility: Yokohama City University Medical Center
city: Kanagawa
country: Japan
facility: Kitasato University Hospital
city: Kyoto
country: Japan
facility: University Hospital Kyoto Prefectural University of Medicine
city: Nara
country: Japan
facility: Nara Medical University Hospital
city: Niigata
country: Japan
facility: Niigata University Medical & Dental Hospital
city: Osaka
country: Japan
facility: Kansai Medical University Hospital
city: Tokyo
country: Japan
facility: Toranomon Hospital
city: Tokyo
country: Japan
facility: The Jikei University Hospital
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: ?ód?
country: Poland
facility: Woj. Wielospec. Centrum Onkologii i Traumatologii
city: Bialystok
country: Poland
facility: Medical University of Bialystok; Oncology clinic
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED, Roman Karaszewski
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
city: Opole
country: Poland
facility: SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii
city: Warszawa
country: Poland
facility: Szpital Sw. Elzbiety - Mokotowskie Centrum Medyczne Sp. z o.o.
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital; Specjalistyczny ul.
city: Moscow
country: Russian Federation
facility: Russian Scientific Center of Roentgenoradiology
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: P.A. Herzen Oncological Inst. ; Oncology
state: Moskovskaja Oblast
city: Sankt-peterburg
country: Russian Federation
facility: SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF
state: Sankt Petersburg
city: Badalona
country: Spain
facility: Institut Catala d?Oncologia Hospital Germans Trias i Pujol
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: Insititut Catala D'Oncologia
state: Barcelona
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
state: Barcelona
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia; Servicio de Oncologia
state: Cordoba
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra; Servicio de Oncologia
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron; Oncology
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial; Servicio de Oncología
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Oncologia
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio; Servicio de Oncologia
city: Bern
country: Switzerland
facility: Inselspital Bern; Universitätsklinik für Medizinische Onkologie, Klinische Forschungseinheit
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen; Onkologie/Hämatologie
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital; Division of Urology
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital, Department of Urology
city: Taipei
country: Taiwan
facility: TAIPEI VETERANS GENERAL HOSPITAL, Urology
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital-LinKou; Urology
city: Blackburn
country: United Kingdom
facility: Royal Blackburn Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Barts and the London NHS Trust.
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital; Institute of Cancer Research
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.