Bladder Cancer Clinical Trial
A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Bladder Cancer Who Are ctDNA Positive Following Cystectomy
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.
Eligibility Criteria
Inclusion Criteria for the Surveillance Phase:
Histologically confirmed MIUC (also termed TCC) of the bladder
TNM classification (based on AJCC Cancer Staging Manual, 8th Edition; Amin et al. 2016) at pathological examination of surgical resection specimen as follows: For patients treated with prior NAC: tumor stage of ypT2-4a or ypN+ and M0. For patients who have not received prior NAC: tumor stage of pT2-4a or pN+ and M0
Surgical resection of MIUC of the bladder
Patients who have received prior platinum-based NAC.
Patients who have not received prior platinum-based NAC, have refused, or are ineligible ("unfit") for cisplatin-based adjuvant chemotherapy.
ctDNA assay developed based on tumor tissue specimen and matched normal DNA from blood.
Tumor PD-L1 expression per 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 patient's 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
ECOG Performance Status of <= 2
Life expectancy >=12 weeks
Adequate hematologic and end-organ function, investigator decision
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs
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. If a cap is in effect limiting enrollment of PD-L1 negative patients, this exclusion criterion will not apply.
Pregnancy or breastfeeding
Positive test for HIV, with the following exception: Patients 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
Patients with active hepatitis B virus or hepatitis C. Patients with past HBV infection or resolved HBV infection are eligible. A negative HBV DNA test must be obtained in these patients prior to enrollment.
Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
Active tuberculosis 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. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. Patients with controlled Type I diabetes mellitus 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 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: Patients 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.
Patients with active hepatitis B virus or hepatitis C
Active tuberculosis confirmed by a test performed within 3 months prior to treatment initiation
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There are 194 Locations for this study
Santa Barbara California, 93105, United States
Littleton Colorado, 80120, United States
Pensacola Florida, 32503, United States
Rockledge Florida, 32955, United States
Las Vegas Nevada, 89102, United States
Winston-Salem North Carolina, 27157, United States
Pittsburgh Pennsylvania, 15212, United States
Austin Texas, 78731, United States
Dallas Texas, 75230, United States
Denton Texas, 76201, United States
Fort Worth Texas, 76104, United States
Houston Texas, 77024, United States
Houston Texas, 77070, United States
McKinney Texas, 75071, United States
Buenos Aires , 1019, Argentina
Buenos Aires , 1426, Argentina
Buenos Aires , C1431, Argentina
Brasschaat , 2930, Belgium
Gent , 9000, Belgium
Roeselare , 8800, Belgium
Fortaleza CE, 60135, Brazil
Fortaleza CE, 60336, Brazil
Uberaba MG, 38082, Brazil
Curitiba PR, 81520, Brazil
Porto Alegre RS, 90035, Brazil
Porto Alegre RS, 90610, Brazil
Porto Alegre RS, 91350, Brazil
Santa Maria RS, 97015, Brazil
Barretos SP, 14784, Brazil
Jau SP, 17210, Brazil
Sao Paulo SP, 01246, Brazil
Sao Paulo SP, 01323, Brazil
São Paulo SP, 01321, Brazil
Edmonton Alberta, T6G 1, Canada
Sudbury Ontario, P3E 5, Canada
Toronto Ontario, M4N 3, Canada
Toronto Ontario, M5G 1, Canada
Montreal Quebec, H3T 1, Canada
Beijing City , 10003, China
Beijing , 10005, China
Changchun , 13002, China
Changsha , 41000, China
Chongqing , 40003, China
Fu Zhou , 35000, China
Fuzhou City , 35000, China
Guangzhou , 51012, China
Harbin , 15008, China
Nanjing City , 21000, China
Nanjing City , 21002, China
Nanjing City , 21110, China
Shanghai City , 20004, China
Shanghai City , 20012, China
Shanghai , 20003, China
Shenyang , 11004, China
Tianjin , 30006, China
Tianjin , 30021, China
Urumqi City , 83001, China
Xiamen , 36100, China
Yantai , 26409, China
Bogota , 11001, Colombia
Medellin , 05002, Colombia
Monteria , 23000, Colombia
Olomouc , 779 0, Czechia
Praha 4 - Krc , 140 5, Czechia
Praha 5 , 150 0, Czechia
Angers , 49055, France
Avignon , 84918, France
Besançon Cedex , 25030, France
Bordeaux , 33075, France
Clermont Ferrand , 63011, France
Lyon , 69373, France
Nancy , 54100, France
Nice , 06189, France
Paris , 75674, France
Suresnes , 92151, France
Toulouse , 31059, France
Villejuif , 94805, France
Düsseldorf , 40225, Germany
Halle (Saale) , 06120, Germany
Herne , 44625, Germany
Jena , 07743, Germany
München , 81675, Germany
Münster , 48149, Germany
Tübingen , 72076, Germany
Ulm , 89081, Germany
Würzburg , 97080, Germany
Athens , 115 2, Greece
Chaidari , 124 6, Greece
Larissa , 411 1, Greece
Patras , 265 0, Greece
Thessaloniki , 54007, Greece
Hong Kong , , Hong Kong
Cork , , Ireland
Dublin , 24, Ireland
Dublin , , Ireland
Haifa , 31096, Israel
Jerusalem , 91120, Israel
Petah Tikva , 49100, Israel
Tel Aviv , 64239, Israel
Napoli Campania, 80131, Italy
Napoli Campania, 80131, Italy
Bologna Emilia-Romagna, 40138, Italy
Meldola Emilia-Romagna, 47014, Italy
Roma Lazio, 00168, Italy
Genova Liguria, 16132, Italy
Milano Lombardia, 20132, Italy
Milano Lombardia, 20141, Italy
Orbassano Piemonte, 10043, Italy
Arezzo Toscana, 52100, Italy
Terni Umbria, 20089, Italy
Padova Veneto, 35128, Italy
Aichi , 466-8, Japan
Chiba , 260-8, Japan
Chiba , 285-8, Japan
Ehime , 791-0, Japan
Fukuoka , 812-8, Japan
Hiroshima , 721-8, Japan
Hiroshima , 730-8, Japan
Hokkaido , 003-0, Japan
Ibaraki , 305-8, Japan
Iwate , 028-3, Japan
Kanagawa , 216-8, Japan
Kanagawa , 238-8, Japan
Kyoto , 606-8, Japan
Nagano , 381-8, Japan
Okayama , 700-8, Japan
Osaka , 541-8, Japan
Osaka , 565-0, Japan
Saitama , 350-1, Japan
Saitama , 362-0, Japan
Shizuoka , 411-8, Japan
Tokushima , 770-8, Japan
Tokyo , 104-0, Japan
Tokyo , 135-8, Japan
Tokyo , 160-8, Japan
Toyama , 930-0, Japan
Daegu , 41404, Korea, Republic of
Goyang-si , 10408, Korea, Republic of
Seoul , 03080, Korea, Republic of
Seoul , 05505, Korea, Republic of
Seoul , 135-7, Korea, Republic of
?ód? , 93-51, Poland
Brzozów , 36-20, Poland
Bydgoszcz , 85-09, Poland
Kraków , 30-72, Poland
Pozna? , 60-56, Poland
Warszawa , 04-07, Poland
Wroc?aw , 53-41, Poland
Obninsk Kaluga, 24903, Russian Federation
Kuzmolovo Leningrad, 18866, Russian Federation
Moscow Moskovskaja Oblast, 11799, Russian Federation
Nizhny Novgorod Niznij Novgorod, 60300, Russian Federation
Saint-Petersburg Sankt Petersburg, 19775, Russian Federation
Ivanovo , 15304, Russian Federation
Murmansk , 18304, Russian Federation
Sabadell Barcelona, 8208, Spain
Santander Cantabria, 39008, Spain
Córdoba Cordoba, 14004, Spain
San Sebastian Guipuzcoa, 20080, Spain
Las Palmas de Gran Canaria LAS Palmas, 35016, Spain
Barcelona , 08035, Spain
Barcelona , 08036, Spain
Barcelona , 08041, Spain
Madrid , 28007, Spain
Madrid , 28033, Spain
Madrid , 28034, Spain
Madrid , 28040, Spain
Madrid , 28041, Spain
Madrid , 28046, Spain
Sevilla , 41013, Spain
Valencia , 46009, Spain
Valencia , 46010, Spain
Adana , 01230, Turkey
Ankara , 06700, Turkey
Ankara , 06800, Turkey
Bakirkoy / Istanbul , 34147, Turkey
Edirne , 22030, Turkey
Istanbul , 34098, Turkey
Kadiköy , 34722, Turkey
Kar??yaka , 35575, Turkey
Samsun , 55200, Turkey
Kharkiv Kharkiv Governorate, 61037, Ukraine
Dnipro KIEV Governorate, 49005, Ukraine
Lviv KIEV Governorate, 79010, Ukraine
Dnipropetrovsk , 49102, Ukraine
Kyiv , 03115, Ukraine
Belfast , BT9 7, United Kingdom
Cambridge , CB2 0, United Kingdom
Edinburgh , EH4 2, United Kingdom
Leeds , LS9 7, United Kingdom
London , EC1M , United Kingdom
London , NW1 2, United Kingdom
London , SW3 6, United Kingdom
London , W6 8R, United Kingdom
Plymouth , PL6 8, United Kingdom
Preston , PR2 9, United Kingdom
Sheffield , S10 2, United Kingdom
Southampton , SO16 , United Kingdom
Sutton , SM2 5, United Kingdom
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