A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in Participants With High-risk Muscle-invasive Bladder Cancer (MIBC) Who Are ctDNA Positive Following Cystectomy
NCT ID: NCT04660344
Last Updated: 2026-02-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
761 participants
INTERVENTIONAL
2021-05-03
2026-09-13
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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Arm A: Atezolizumab
Atezolizumab will be administered intravenously (IV) at a dose of 1680 milligrams (mg) on Day 1 of each 28-day cycle for 12 cycles or up to 1 year (whichever occurs first). Atezolizumab will be discontinued in the event of disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.
Atezolizumab
ctDNA positive participants will receive 1680 mg IV, every 4 weeks (Q4W) on Day 1 of each 28-day cycle.
Signatera
Signatera will be used to evaluate whether ctDNA is detected during serial monitoring of peripheral blood samples for participants enrolled in surveillance. Participants with a ctDNA positive result will be screened for inclusion in the treatment phase. Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter follow-up.
Arm B: Placebo
Placebo will be administered IV on Day 1 of each 28-day cycle. Placebo will be discontinued in the event of disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.
Placebo
ctDNA positive participants will receive placebo IV, Q4W on Day 1 of each 28-day cycle
Signatera
Signatera will be used to evaluate whether ctDNA is detected during serial monitoring of peripheral blood samples for participants enrolled in surveillance. Participants with a ctDNA positive result will be screened for inclusion in the treatment phase. Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter follow-up.
Arm C: Surveillance Follow-Up
Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter follow-up.
Signatera
Signatera will be used to evaluate whether ctDNA is detected during serial monitoring of peripheral blood samples for participants enrolled in surveillance. Participants with a ctDNA positive result will be screened for inclusion in the treatment phase. Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter follow-up.
Interventions
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Atezolizumab
ctDNA positive participants will receive 1680 mg IV, every 4 weeks (Q4W) on Day 1 of each 28-day cycle.
Placebo
ctDNA positive participants will receive placebo IV, Q4W on Day 1 of each 28-day cycle
Signatera
Signatera will be used to evaluate whether ctDNA is detected during serial monitoring of peripheral blood samples for participants enrolled in surveillance. Participants with a ctDNA positive result will be screened for inclusion in the treatment phase. Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter follow-up.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Tumor, nodes, and metastases (TNM) classification (based on American Joint Committee on Cancer \[AJCC\] Cancer Staging Manual, 8th Edition; Amin et al. 2016) at pathological examination of surgical resection specimen as follows: For participants treated with prior neoadjuvant chemotherapy (NAC): tumor stage of ypT2-4a or ypN+ and M0. For participants who have not received prior NAC: tumor stage of pT2-4a or pN+ and M0
* Surgical resection of MIUC of the bladder
* Participants who have not received prior platinum-based NAC must be ineligible for cisplatin-based adjuvant chemotherapy, have refused it, or will not receive it based on physician's decision
* ctDNA assay developed based on tumor tissue specimen and matched normal DNA from blood
* Tumor programmed death ligand (PD-L1) expression per immunohistochemistry (IHC) that is evaluable by central testing of a representative tumor tissue specimen
* Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pelvis, abdomen, and chest no more than 4 weeks prior to enrollment
* Full recovery from cystectomy and enrollment within 24 weeks following cystectomy. Minimum of 6 weeks must have elapsed from surgery
* Blood for plasma ctDNA sample evaluated to be ctDNA positive, defined as the presence of two or more mutations out of the 16 mutations identified based on participant' whole exome sequencing (WES) evaluable (ctDNA assay designability) report
* Absence of residual disease and absence of metastasis, as confirmed by a negative baseline CT or MRI scan of the pelvis, abdomen, and chest no more than 28 days prior to randomization, as assessed by the investigator and Independent Review Facility
* Eastern cooperative oncology group (ECOG) performance status of ≤ 2
* Life expectancy ≥12 weeks
* Adequate hematologic and end-organ function
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs
Exclusion Criteria
* Pregnancy or breastfeeding
* Positive test for human immunodeficiency virus (HIV), with the following exception: Participants with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy, have a cluster of differentiation 4 (CD4) count ≥ 200 per microliter (/µL), and have an undetectable viral load
* Participants with active hepatitis B virus (HBV) or hepatitis C virus (HCV). Participants with past HBV infection or resolved HBV infection are eligible. A negative HBV deoxyribonucleic acid (DNA) test must be obtained in these participants prior to enrollment. Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
* Active tuberculosis (TB) confirmed by a test performed within 3 months prior to treatment initiation
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
* History of autoimmune disease. Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. Participants with controlled type I diabetes mellitus (T1DM) on a stable dose of insulin regimen may be eligible for this study
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction (MI) within the previous 3 months, unstable arrhythmias, or unstable angina
* Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to study enrollment
* Adjuvant chemotherapy or radiation therapy for UC following cystectomy
* Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or 5 half-lives of the drug, whichever is longer, prior to enrollment
* Malignancies other than UC within 5 years prior to study enrollment
* Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to randomization to the treatment phase. Hormone-replacement therapy or oral contraceptives are allowed
* Adjuvant chemotherapy or radiation therapy for UC following cystectomy
* Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or 5 half-lives of the drug, whichever is longer, prior to randomization to the treatment phase
* Positive test for HIV, with the following exception: Participants with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy, have a CD4 count ≥200/μL, and have an undetectable viral load
* Participants with active HBV or HCV
* Active tuberculosis confirmed by a test performed within 3 months prior to treatment initiation
18 Years
ALL
No
Sponsors
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Natera, Inc.
INDUSTRY
Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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Hospital Universitario Marques de Valdecilla
Santander, Cantabria, Spain
Hospital Universitario Reina Sofia
Córdoba, Cordoba, Spain
Hospital de Donostia
Donostia / San Sebastian, Guipuzcoa, Spain
Hospital Universitari Vall d'Hebron
Barcelona, , Spain
Hospital Clínic i Provincial
Barcelona, , Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, , Spain
Hospital Ramon y Cajal
Madrid, , Spain
Hospital Clinico San Carlos
Madrid, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Hospital Universitario La Paz
Madrid, , Spain
Hospital Universitario Virgen del Rocio
Seville, , Spain
Instituto Valenciano Oncologia
Valencia, , Spain
Hospital Clinico Universitario de Valencia
Valencia, , Spain
Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital
Adana, , Turkey (Türkiye)
Ankara University Faculty of Medicine Cebeci Hospital
Ankara, , Turkey (Türkiye)
Ankara City Hospital
Ankara, , Turkey (Türkiye)
Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji
Bakirkoy / Istanbul, , Turkey (Türkiye)
Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
Edirne, , Turkey (Türkiye)
Istanbul University Cerrahpasa Faculty of Medicine
Istanbul, , Turkey (Türkiye)
Medeniyet University Goztepe Training and Research Hospital.
Istanbul, , Turkey (Türkiye)
Medikal Park Izmir Hospital
Karşıyaka, , Turkey (Türkiye)
Medikal Park Samsun
Samsun, , Turkey (Türkiye)
UCLA Department of Medicine
Santa Monica, California, United States
Rocky Mountain Cancer Center - Denver
Littleton, Colorado, United States
Cancer Care Centers of Brevard
Rockledge, Florida, United States
Optum Health Care
Las Vegas, Nevada, United States
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States
Cleveland Clinic
Cleveland, Ohio, United States
AHN Cancer Institute ? Allegheny General Hospital
Pittsburgh, Pennsylvania, United States
Centro Medico Austral
Buenos Aires, , Argentina
Instituto Alexander Fleming
Buenos Aires, , Argentina
AZ KLINA
Brasschaat, , Belgium
UZ Gent
Ghent, , Belgium
AZ Delta (Campus Rumbeke)
Roeselare, , Belgium
Oncocentro Serviços Medicos E Hospitalares Ltda
Fortaleza, Ceará, Brazil
CETUS Hospital Dia Oncologia
Belo Horizonte, Minas Gerais, Brazil
Hospital Erasto Gaertner
Curitiba, Paraná, Brazil
Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, Brazil
Hospital Sao Lucas - PUCRS
Porto Alegre, Rio Grande do Sul, Brazil
Hospital Nossa Senhora da Conceicao
Porto Alegre, Rio Grande do Sul, Brazil
*X*Fundação Pio XII Hospital de Câncer de Barretos
Barretos, São Paulo, Brazil
Hospital Amaral Carvalho
Jaú, São Paulo, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
São Paulo, São Paulo, Brazil
Hospital Alemao Oswaldo Cruz
São Paulo, São Paulo, Brazil
Friendship Hospital, Capital Medical University
Beijing, , China
the First Hospital of Jilin University
Changchun, , China
Hu Nan Provincial Cancer Hospital
Changsha, , China
Chongqing Cancer Hospital
Chongqing, , China
Fujian Medical University Union Hospital
Fujian, , China
The First Affiliated Hospital of Fujian Medical University
Fuzhou, , China
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, , China
Jiangsu Cancer Hospital
Nanjing, , China
Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
Nanjing, , China
Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
Nanjing, , China
Zhongshan Hospital Fudan University
Shanghai, , China
Fudan University Shanghai Cancer Center
Shanghai, , China
Liaoning cancer Hospital & Institute
Shenyang, , China
Tianjin Cancer Hospital
Tianjin, , China
Yantai Yu Huangding Hospital
Yantai, , China
Clinica del Country
Bogotá, , Colombia
Instituto Cancerología Medellin
Medellín, , Colombia
Oncomedica S.A.
Montería, , Colombia
Fakultni nemocnice Olomouc
Olomouc, , Czechia
Fakultni nemocnice v Motole
Prague, , Czechia
Fakultni Thomayerova nemocnice
Praha 4 - Krc, , Czechia
ICO Paul Papin
Angers, , France
Institut Sainte Catherine
Avignon, , France
Hopital Saint Andre
Bordeaux, , France
Centre Jean Perrin
Clermont-Ferrand, , France
Centre Léon Bérard
Lyon, , France
Centre D'Oncologie de Gentilly
Nancy, , France
Centre Antoine Lacassagne
Nice, , France
Institut Mutualiste Montsouris
Paris, , France
Hopital Foch
Suresnes, , France
Institut Claudius Régaud
Toulouse, , France
Institut Gustave Roussy
Villejuif, , France
Universitätsklinikum Düsseldorf
Düsseldorf, , Germany
Krankenhaus Martha-Maria Halle-Dölau, Klinik für Urologie
Halle, , Germany
Universitätsklinikum der Ruhr-Universität Bochum, Marien-Hospital Herne, Urologische Klinik
Herne, , Germany
Klinikum rechts der Isar der TU München
München, , Germany
Universitätsklinikum Tübingen
Tübingen, , Germany
Universitätsklinikum Ulm
Ulm, , Germany
Universitätsklinikum Würzburg
Würzburg, , Germany
Attikon University General Hospital
Ahens, , Greece
Alexandras General Hospital of Athens
Athens, , Greece
University Hospital of Larissa
Larissa, , Greece
University Hospital of Patras Medical Oncology
Pátrai, , Greece
Theageneio Hospital
Thessaloniki, , Greece
Queen Mary Hospital
Hong Kong, , Hong Kong
Cork Uni Hospital
Cork, , Ireland
Adelaide & Meath Hospital, Dublin, Incorporating the National Children's Hospital
Dublin, , Ireland
Rambam Medical Center
Haifa, , Israel
Tel Aviv Sourasky Medical Ctr
Tel Aviv, , Israel
Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli", Day Hospital Oncologico
Napoli, Campania, Italy
Istituto Nazionale Tumori Irccs Fondazione G. Pascale
Napoli, Campania, Italy
AZ.Osp S. Orsola Malpighi-Reparto di Oncologia Medica
Bologna, Emilia-Romagna, Italy
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
Meldola, Emilia-Romagna, Italy
Policlinico Universitario "Agostino Gemelli"
Rome, Lazio, Italy
A.O. Universitaria S. Martino Di Genova
Genoa, Liguria, Italy
Irccs Ospedale San Raffaele
Milan, Lombardy, Italy
Irccs Istituto Nazionale Dei Tumori (Int)
Milan, Lombardy, Italy
Istituto Europeo Di Oncologia
Milan, Lombardy, Italy
A.O. Universitaria S. Luigi Gonzaga
Orbassano, Piedmont, Italy
Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato
Arezzo, Tuscany, Italy
Azienda Ospedaliera Santa Maria di Terni
Terni, Umbria, Italy
IOV - Istituto Oncologico Veneto - IRCCS
Padua, Veneto, Italy
Nagoya University Hospital
Aichi, , Japan
Chiba Cancer Center
Chiba, , Japan
Toho University Sakura Medical Center
Chiba, , Japan
Shikoku Cancer Center
Ehime, , Japan
Kyushu University Hospital
Fukuoka, , Japan
Fukuyama City Hospital
Hiroshima, , Japan
Hiroshima City Hiroshima Citizens Hospital
Hiroshima, , Japan
National Hospital Organization Hokkaido Cancer Center
Hokkaido, , Japan
University of Tsukuba Hospital
Ibaraki, , Japan
St. Marianna University Hospital
Kanagawa, , Japan
Yokosuka Kyosai Hospital
Kanagawa, , Japan
Kyoto University Hospital
Kyoto, , Japan
Nagano Municipal Hospital
Nagano, , Japan
Iwate Medical University Hospital
Numakunai, , Japan
Okayama University Hospital
Okayama, , Japan
Osaka International Cancer Institute
Osaka, , Japan
Saitama Medical University International Medical Center
Saitama, , Japan
Saitama Cancer Center
Saitama, , Japan
Shizuoka Cancer Center
Shizuoka, , Japan
Tokushima University Hospital
Tokushima, , Japan
National Cancer Center Hospital
Tokyo, , Japan
Keio University Hospital
Tokyo, , Japan
Toyama University Hospital
Toyama, , Japan
CUAN Hospital
San Pedro Garza García, Nuevo León, Mexico
PRATIA MCM Kraków
Krakow, , Poland
Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu
Poznan, , Poland
Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
Warsaw, , Poland
Dolnoslaskie Centrum Onkologii
Wroclaw, , Poland
St-Petersburg Regional Oncology Dispensary
Kuzmolovo, Leningrad, Russia
Privolzhsk Regional Medical Center
Nizhny Novgorod, Niznij Novgorod, Russia
FSI Russian Centre of Radiology and Surgical Technologies
Saint Petersburg, Sankt-Peterburg, Russia
Ivanovo Regional Oncology Dispensary
Ivanovo, , Russia
Murmansk Regional Clinical Hospital named after P.A. Bayandin
Murmansk, , Russia
National Cancer Centre
Singapore, , Singapore
National Cancer Center
Goyang-si, , South Korea
Samsung Medical Center
Seoul, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Asan Medical Center
Seoul, , South Korea
Corporacio Sanitaria Parc Tauli
Sabadell, Barcelona, Spain
Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval Department of Urology #4
Kharkiv, Kharkiv Governorate, Ukraine
ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council
Dnipro, KIEV Governorate, Ukraine
Lviv Regional Clinical Hospital
Lviv, KIEV Governorate, Ukraine
CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC SI Dnipropetrovsk MA of MOHU Ch of Oncology and MR
Dnipropetrovsk, , Ukraine
Kyiv City Clinical Oncological Center
Kyiv, , Ukraine
Addenbrookes Hospital
Cambridge, , United Kingdom
Western General Hospital
Edinburgh, , United Kingdom
Barts Hospital
London, , United Kingdom
University College London NHS Foundation Trust
London, , United Kingdom
Royal Marsden Hospital - London
London, , United Kingdom
Charing Cross Hospital
London, , United Kingdom
Derriford Hospital
Plymouth, , United Kingdom
Royal Preston Hospital
Preston, , United Kingdom
Weston Park Hospital
Sheffield, , United Kingdom
Southampton University Hospitals NHS Trust
Southampton, , United Kingdom
Royal Marsden Hospital (Sutton)
Sutton, , United Kingdom
Countries
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References
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Powles T, Kann AG, Castellano D, Gross-Goupil M, Nishiyama H, Bracarda S, Bjerggaard Jensen J, Makaroff L, Jiang S, Ku JH, Park SH, Reig Torras O, Ye D, Maruzzo M, Necchi A, Morales-Barrera R, Giunta EF, Lee JL, Tortora G, Urun Y, Dolowy L, Erdem D, Pinto A, Grando F, Zou W, Assaf ZJ, Vuky J, Degaonkar V, Steinberg EE, Bellmunt J, Gschwend JE; IMvigor011 Investigators. ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer. N Engl J Med. 2025 Dec 18;393(24):2395-2408. doi: 10.1056/NEJMoa2511885. Epub 2025 Oct 20.
Jackson-Spence F, Toms C, O'Mahony LF, Choy J, Flanders L, Szabados B, Powles T. IMvigor011: a study of adjuvant atezolizumab in patients with high-risk MIBC who are ctDNA+ post-surgery. Future Oncol. 2023 Mar;19(7):509-515. doi: 10.2217/fon-2022-0868. Epub 2023 Apr 21.
Other Identifiers
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2020-004418-36
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2022-502705-15-00
Identifier Type: CTIS
Identifier Source: secondary_id
BO42843
Identifier Type: -
Identifier Source: org_study_id
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