A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Bladder Cancer Who Are ctDNA Positive Following Cystectomy
- Conditions
- Muscle-invasive Bladder Cancer
- Interventions
- Registration Number
- NCT04660344
- Lead Sponsor
- Hoffmann-La Roche
- Brief 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 ctDNA positive and are at high risk for recurrence following cystectomy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 761
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Atezolizumab Atezolizumab Atezolizumab will be administered intravenously 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. Arm A: Atezolizumab Signatera Atezolizumab will be administered intravenously 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. Arm B: Placebo Placebo Placebo will be administered intravenously 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. Arm B: Placebo Signatera Placebo will be administered intravenously 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. Arm C: Surveillance Follow-Up Signatera Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter follow-up.
- Primary Outcome Measures
Name Time Method Investigator-assessed DFS Randomization up to first occurrence of DFS event (up to approximately 40 months) Investigator-assessed disease-free survival (DFS), defined as the time from randomization to the first occurrence of a DFS event, defined as any of the following:
* Local (pelvic) recurrence of urothelial carcinoma (UC) (including soft tissue and regional lymph nodes)
* Urinary tract recurrence of UC (including all pathological stages and grades)
* Distant metastasis of UC
* Death from any cause
- Secondary Outcome Measures
Name Time Method Overall survival (OS) Randomization up to death from any cause (up to approximately 10 years) Overall survival (OS), defined as the time from randomization to death from any cause.
Independent Review Facility (IRF)-Assessed DFS Randomization up to first occurrence of DFS event (up to approximately 40 months) Investigator-Assessed Disease-Specific Survival Randomization to death from UC (up to approximately 10 years) Investigator-assessed disease-specific survival, defined as the time from randomization to death from UC per investigator assessment of cause of death.
Investigator-Assessed Distant Metastasis-Free Survival Randomization to diagnosis of distant metastases or death from any cause (up to approximately 10 years) Investigator-assessed distant metastasis-free survival, defined as the time from randomization to the diagnosis of distant (i.e., non-locoregional) metastases or death from any cause.
Time to Confirmed Deterioration of Function and Health Related Quality of Life (HRQoL) Randomization to participant's first score decrease of >=10 points from Baseline on EORTC QLQ-C30 physical function scale, role function scale, and the GHS/QoL Scale (up to approximately 10 years) Time to confirmed deterioration of function and health-related quality of life (HRQoL), defined as the time from randomization to the date of a participant's first score decrease of \>= 10 points from baseline on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) physical function scale, role function scale, and the global health status (GHS)/QoL scale (separately), held for at least two consecutive time points or followed by death.
ctDNA Clearance Baseline, Cycle 3 Day 1 or Cycle 5 Day 1 (each cycle is 28 days) ctDNA clearance, defined as the proportion of patients who are ctDNA positive at baseline and ctDNA negative at Cycle 3, Day 1 or Cycle 5, Day 1.
Percentage of Participants With Adverse Events Baseline up to approximately 10 years Serum Concentration of Atezolizumab At pre-defined intervals from first administration of study drug up to approximately 10 years Incidence of Anti-Drug Antibodies (ADAs) to Atezolizumab Baseline up to approximately 10 years Incidence of anti-drug antibodies (ADAs) to atezolizumab after initiation of study treatment (postbaseline incidence).
Prevalence of ADAs to Atezolizumab Baseline Prevalence of ADAs to atezolizumab at baseline.
Trial Locations
- Locations (167)
Medikal Park Samsun
🇹🇷Samsun, Turkey
Beneficencia Portuguesa de Sao Paulo
🇧🇷São Paulo, Brazil
Rocky Mountain Cancer Center - Denver
🇺🇸Littleton, Colorado, United States
UCLA Department of Medicine
🇺🇸Santa Monica, California, United States
Instituto Nacional de Cancerologia
🇲🇽Mexico City, Mexico
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
🇧🇪Gent, 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
🇧🇷Jau, São Paulo, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, São Paulo, Brazil
Hospital Alemao Oswaldo Cruz
🇧🇷Sao 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
🇨🇳Fu Zhou, China
Fujian Medical University Union Hospital
🇨🇳Fujian, China
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, China
PRATIA MCM Kraków
🇵🇱Kraków, Poland
Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
🇨🇳Nanjing City, China
Jiangsu Cancer Hospital
🇨🇳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
🇨🇴Bogota, Colombia
Instituto Cancerología Medellin
🇨🇴Medellin, Colombia
Oncomedica S.A.
🇨🇴Monteria, Colombia
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Fakultni Thomayerova nemocnice
🇨🇿Praha 4 - Krc, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha 5, 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 (Saale), 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
🇬🇷Patras, 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"
🇮🇹Roma, Lazio, Italy
A.O. Universitaria S. Martino Di Genova
🇮🇹Genova, Liguria, Italy
Irccs Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
Irccs Istituto Nazionale Dei Tumori (Int)
🇮🇹Milano, Lombardia, Italy
Istituto Europeo Di Oncologia
🇮🇹Milano, Lombardia, Italy
A.O. Universitaria S. Luigi Gonzaga
🇮🇹Orbassano, Piemonte, Italy
Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato
🇮🇹Arezzo, Toscana, 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
Medikal Park Izmir Hospital
🇹🇷Kar??yaka, Turkey
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
Iwate Medical University Hospital
🇯🇵Iwate, Japan
St. Marianna University Hospital
🇯🇵Kanagawa, Japan
Yokosuka Kyosai Hospital
🇯🇵Kanagawa, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Nagano Municipal Hospital
🇯🇵Nagano, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Osaka University Hospital
🇯🇵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
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Keio University Hospital
🇯🇵Tokyo, Japan
Toyama University Hospital
🇯🇵Toyama, Japan
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Centro Medico Nacional Siglo Xxi - Imss
🇲🇽Mexico City, Mexico CITY (federal District), Mexico
Inst. Nacional de La Nutricion Salvador Zubiran
🇲🇽Mexico City, Mexico CITY (federal District), Mexico
CUAN Hospital
🇲🇽San Pedro Garza García, Nuevo LEON, Mexico
Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu
🇵🇱Pozna?, Poland
Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.
🇵🇱Warszawa, Poland
Dolno?l?skie Centrum Onkologii, Pulmonologii i Hematologii
🇵🇱Wroc?aw, Poland
St-Petersburg Regional Oncology Dispensary
🇷🇺Kuzmolovo, Leningrad, Russian Federation
Privolzhsk Regional Medical Center
🇷🇺Nizhny Novgorod, Niznij Novgorod, Russian Federation
FSI Russian Centre of Radiology and Surgical Technologies
🇷🇺Saint-Petersburg, Sankt Petersburg, Russian Federation
Ivanovo Regional Oncology Dispensary
🇷🇺Ivanovo, Russian Federation
Murmansk Regional Clinical Hospital named after P.A. Bayandin
🇷🇺Murmansk, Russian Federation
National Cancer Centre
🇸🇬Singapore, Singapore
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
🇪🇸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
🇪🇸Sevilla, 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
Ankara University Faculty of Medicine Cebeci Hospital
🇹🇷Ankara, Turkey
Ankara City Hospital
🇹🇷Ankara, Turkey
Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji
🇹🇷Bakirkoy / Istanbul, Turkey
Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
🇹🇷Edirne, Turkey
Istanbul University Cerrahpasa Faculty of Medicine
🇹🇷Istanbul, Turkey
Medeniyet University Goztepe Training and Research Hospital.
🇹🇷Istanbul, Turkey
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