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NCT04660344

PHASE3

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

Sponsor: Hoffmann-La Roche

View on ClinicalTrials.gov

Summary

This is a global Phase III, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with placebo in participants with MIBC who are circulating tumour deoxyribonucleic acid (ctDNA) positive and are at high risk for recurrence following cystectomy.

Official title: A Phase III, Double-blind, Multicenter, Randomized Study of Atezolizumab (Anti-PDL1 Antibody) Versus Placebo as Adjuvant Therapy in Patients With High-risk Muscle-invasive Bladder Cancer Who Are ctDNA Positive Following Cystectomy

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

761

Start Date

2021-05-03

Completion Date

2026-10-01

Last Updated

2026-03-27

Healthy Volunteers

Conditions

Muscle-invasive Bladder Cancer

Interventions

DRUG

Atezolizumab

ctDNA positive participants will receive 1680 mg IV, every 4 weeks (Q4W) on Day 1 of each 28-day cycle.

OTHER

Placebo

ctDNA positive participants will receive placebo IV, Q4W on Day 1 of each 28-day cycle

DEVICE

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 surveillance follow-up.

Inclusion Criteria: Inclusion Criteria for the Surveillance Phase: * Histologically confirmed MIUC (also termed transitional cell carcinoma \[TCC\]) of the bladder * 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 Additional Inclusion Criteria for the Treatment Phase: * 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: General Medical Exclusion Criteria for the Surveillance Phase: * Known PD-L1 IHC result for adjuvant therapy. The decision for the adjuvant therapy should not be based on the PD-L1 IHC result * 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 Cancer-Specific Exclusion Criteria for the Surveillance Phase: * 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 Additional Exclusion Criteria for the Treatment Phase: * 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

Locations (148)

Cancer Care Centers of Brevard

Rockledge, Florida, United States

Optum Health Care

Las Vegas, Nevada, 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

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

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

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

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

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

Tel Aviv Sourasky Medical Ctr

Tel Aviv, Israel

Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli", Day Hospital Oncologico

Naples, Campania, Italy

Istituto Nazionale Tumori Irccs Fondazione G. Pascale

Naples, 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

Padova, Veneto, Italy

Nagoya University Hospital

Aichi, Japan

Chiba Cancer Center

Chiba, Japan

Toho University Sakura Medical Center

Chiba, Japan

Shikoku Cancer Center

Ehime, 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

Osaka International Cancer Institute

Osaka, Japan

Saitama Medical University International Medical Center

Saitama, Japan

Saitama Cancer Center

Saitama, Japan

Shizuoka Cancer Center

Shizuoka, 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

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

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)

Medikal Park Izmir Hospital

Cordaleo, 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 Samsun

Samsun, Turkey (Türkiye)

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

Clinical Research Directory

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

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (148)