A Study of Atezolizumab Versus Observation as Adjuvant Therapy in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (UC) After Surgical Resection

Carcinoma, Transitional Cell Clinical Trial

— IMvigor010  

Official title:

A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Urothelial Carcinoma After Surgical Resection

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02450331
• Other study ID #: WO29636
• Secondary ID: 2014-005603-25
• Status: Terminated
• Phase: Phase 3
• Start date: October 5, 2015
• Est. completion date: June 14, 2022

Study information

• Verified date: May 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase III, open-label, randomized, multicenter study is to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with observation in participants with muscle-invasive UC who are at high risk for recurrence following resection. Eligible participants were randomized by a 1:1 ratio into atezolizumab group or control group.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 809
• Est. completion date: June 14, 2022
• Est. primary completion date: November 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma) of the bladder or upper urinary tract (i.e., renal pelvis or ureters)

• For participants treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-4a or ypN+ (ypT2-4 or ypN+ for participants with upper urinary tract UC) and M0

• For participants who have not received prior neoadjuvant chemotherapy: tumor stage of pT3-4a or pN+ (pT3-4 or pN+ for participants with upper urinary tract UC) and M0

• Representative formalin-fixed paraffin-embedded tumor specimens from surgical resection (i.e., radical cystectomy, nephroureterectomy, or lymph node dissection) in paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for central testing and determined to be evaluable for tumor programmed death-ligand 1 (PD-L1) expression prior to study enrollment

• Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging scan of the pelvis, abdomen, and chest no more than 4 weeks prior to randomization

• Full recovery from cystectomy or nephroureterectomy within 14 weeks following surgery

• Eastern Cooperative Oncology Group performance status of less than or equal to (</=) 2

• Life expectancy greater than or equal to (>/=) 12 weeks

• Adequate hematologic and end-organ function

• For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (<) 1 percent (%) per year during the treatment period and for at least 5 months after the last dose of atezolizumab

Exclusion Criteria:

• Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment

• Adjuvant chemotherapy or radiation therapy for UC following surgical resection

• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug prior to enrollment

• Malignancies other than UC within 5 years prior to Cycle 1, Day 1

• Pregnancy or breastfeeding

• Significant cardiovascular disease

• Severe infections within 4 weeks prior to Cycle 1, Day 1

• Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1

• 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

• Prior allogeneic stem cell or solid organ transplant

• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan

• Positive test for human immunodeficiency virus and/or active hepatitis B or hepatitis C or tuberculosis

• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1

• Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-CD40, anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered at a dose of 1200 milligrams (mg).

Locations

Country	Name	City	State
Australia	Monash Medical Centre; Oncology	Clayton	Victoria
Australia	Royal Brisbane & Women's Hosp; Cancer Care Serv	Herston	Queensland
Australia	Macquarie University Hospital	Macquarie Park	New South Wales
Australia	Austin and Repatriation Medical Centre; Cancer Services	Melbourne	Victoria
Belgium	Institut Jules Bordet	Anderlecht
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	UZ Gent	Gent
Belgium	UZ Leuven Gasthuisberg	Leuven
Canada	Royal Victoria Hospital	Barrie	Ontario
Canada	Cross Cancer Institute ; Dept of Medical Oncology	Edmonton	Alberta
Canada	London Regional Cancer Centre	London	Ontario
Canada	McGill University; Glen Site; Oncology	Montreal	Quebec
Canada	Lakeridge Health Oshawa; Oncology	Oshawa	Ontario
Canada	The Ottawa Hospital Cancer Centre; Oncology	Ottawa	Ontario
Canada	CHU de Quebec Hotel-Dieu de Quebec	Quebec City	Quebec
Canada	North York General Hospital	Toronto	Ontario
Canada	Sunnybrook Odette Cancer Centre	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
China	Beijing Cancer Hospital	Beijing
China	Friendship Hospital, Capital Medical University	Beijing
China	Peking University First Hospital	Beijing City
China	The Second Affiliated Hospital, Sun Yat-sen University	Guangzhou City
China	Jiangsu Province Hospital	Nanjing
China	Jiangsu Cancer Hospital	Nanjing City
China	Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai City
China	Huashan Hospital Affiliated to Fudan University	Shanghai City
Czechia	Masarykuv onkologicky ustav	Brno
Czechia	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc
Czechia	Multiscan s.r.o.	Pardubice
Czechia	University Hospital Motol; Department of Urology	Praha 5
Finland	Helsinki University Central Hospital; Urology Clinics	Helsinki
Finland	Tampere University Hospital; Dept Of Urology	Tampere
Finland	Turku University Central Hospital; Urology clinic	Turku
France	ICO Paul Papin; Oncologie Medicale.	Angers
France	Institut Sainte Catherine;Recherche Clinique	Avignon
France	Hopital Saint Andre	Bordeaux
France	Centre Francois Baclesse; Recherche Clinique	Caen
France	Centre Jean Perrin	Clermont Ferrand
France	Centre Leon Berard; Departement Oncologie Medicale	Lyon
France	Centre D'Oncologie de Gentilly; Oncology	Nancy
France	Centre Antoine Lacassagne	Nice
France	Hopital Cochin; Unite Fonctionnelle D Oncologie	Paris
France	Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale	Paris
France	Hopital Saint Louis; Oncologie Medicale	Paris
France	Institut Mutualiste Montsouris; Oncologie	Paris
France	ICO - Site René Gauducheau	Saint Herblain
France	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse
Germany	Campus Charitè Mitte Charité Centrum 10. Klinik f.Urologie	Berlin
Germany	Augusta-Kranken-Anstalt gGmbH; Klinik für Hämatologie, Onkologie & Palliativmedizin	Bochum
Germany	Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie	Dresden
Germany	Universitätsklinikum Düsseldorf; Urologische Klinik	Düsseldorf
Germany	Universitätsklinikum der Ruhr-Universität Bochum, Marien-Hospital Herne, Urologische Klinik	Herne
Germany	Medizinische Fakultät Mannheim, Universitätsklinikum Mannheim, Klinik für Urologie	Mannheim
Germany	Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik	München
Germany	Universitätsmedizin Rostock, Urologische Klinik und Poliklinik	Rostock
Germany	Diakonie-Klinikum Stuttgart; Urologische Klinik	Stuttgart
Germany	Universitätsklinikum Tübingen; Klinik für Urologie	Tübingen
Germany	Universitätsklinikum Ulm; Klinik für Urologie	Ulm
Greece	Alexandras General Hospital of Athens; Oncology Department	Athens
Greece	University Hospital of Patras Medical Oncology	Patras
Israel	Rambam Health Care Campus; Oncology - Hafia	Hafia
Israel	Hadassah Ein Karem Hospital; Oncology Dept	Jerusalem
Israel	Meir Medical Center; Oncology	Kfar-Saba
Israel	Rabin Medical Center; Oncology Dept	Petah Tikva
Israel	Chaim Sheba Medical Center; Oncology Dept	Ramat Gan
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
Israel	Assaf Harofeh; Oncology	Zerifin
Italy	Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia	Arezzo	Toscana
Italy	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica	Bologna	Emilia-Romagna
Italy	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche	Milano	Lombardia
Italy	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia
Italy	Az. Osp. Cardarelli; Divisione Di Oncologia	Napoli	Campania
Italy	ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE; Dipartimento Uro-Ginecologico	Napoli	Campania
Italy	A.O. UNIVERSITARIA S. LUIGI GONZAGA; Oncologia Medica	Orbassano	Piemonte
Italy	Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica	Roma	Lazio
Italy	Azienda Ospedaliera S. Maria - Terni; Oncologia	Terni	Umbria
Japan	Nagoya University Hospital; Urology	Aichi
Japan	Hirosaki University School of Medicine & Hospital; Urology	Aomori
Japan	Shikoku Cancer Center	Ehime
Japan	Hiroshima City Hiroshima Citizens Hospital; Urology	Hiroshima
Japan	National Hospital Organization Hokkaido Cancer Center	Hokkaido
Japan	University of Tsukuba Hospital	Ibaraki
Japan	Iwate Medical University Hospital; Urology	Iwate
Japan	Kyoto University Hospital	Kyoto
Japan	Okayama University Hospital	Okayama
Japan	Kindai University Hospital; Urology	Osaka
Japan	Osaka University Hospital; Urology	Osaka
Japan	Saitama Medical University International Medical Center	Saitama
Japan	Shizuoka Cancer Center; Urology	Shizuoka
Japan	Kyorin University Hospital	Tokyo
Japan	National Cancer Center Hospital; Urology	Tokyo
Japan	The Cancer Institute Hospital, JFCR; Urology	Tokyo
Japan	The University of Tokyo Hospital	Tokyo
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Netherlands	NKI/AvL	Amsterdam
Netherlands	VU MEDISCH CENTRUM; Dept. of Medical Oncology	Amsterdam
Netherlands	Academ Ziekenhuis Groningen; Medical Oncology	Groningen
Netherlands	Erasmus Mc - Daniel Den Hoed Kliniek; Interne Oncologie	Rotterdam
Netherlands	St. Antonius locatie Leidsche Rijn	Utrecht
Poland	KO-MED Centra Kliniczne Lublin II	Lublin
Poland	Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu; Oddzia? Chemioterapii	Pozna?
Poland	SpecjalistycznySzpital Miejski w Toruniu; Oddzia? Urologii Ogólnej i Onkologicznej	Toru?
Poland	Szpital Kliniczny Dzieci?tka Jezus; Oddzia? Urologii	Warszawa
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego; Oddzial Urologii i Onkologii	Wroclaw
Russian Federation	Sverdlovsk Regional Oncology Dispensary; Chemotherapy	Ekaterinburg	Sverdlovsk
Russian Federation	Ivanovo Regional Oncology Dispensary	Ivanovo
Russian Federation	P.A. Herzen Oncological Inst. ; Oncology	Moscow	Moskovskaja Oblast
Russian Federation	Privolzhsk Regional Medical Center	Nizhny Novgorod	Niznij Novgorod
Russian Federation	SBEI of HPE ?Bashkir State Medical University? of MoH RF	UFA	Baskortostan
Serbia	Clinic for Urology; Clinical Hospital Center "Dragisa Misovic-Dedinje"	Belgrade
Serbia	Clinical Center of Serbia; Clinic of Urology	Belgrade
Spain	Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona
Spain	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona
Spain	Hospital de Donostia; Servicio de Oncologia Medica	San Sebastian	Guipuzcoa
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Sant Andreu de La Barca	Barcelona
Spain	Instituto Valenciano Oncologia; Oncologia Medica	Valencia
Switzerland	UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie	Zürich
Taiwan	Taichung Veterans General Hospital; Division of Urology	Taichung
Taiwan	National Taiwan University Hospital, Department of Urology	Taipei
Turkey	Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology	Adana
Turkey	Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department	Edirne
Turkey	Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology	Istanbul
Turkey	Medikal Park Izmir Hospital	Kar??yaka
Ukraine	CI Dnipropetrovsk CMCH #4 MA of MOHU Ch of Oncology and MR	Dnipropetrovsk
Ukraine	Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval Department of Urology #4	Kharkiv	Kharkiv Governorate
Ukraine	GU "Institution of urology of Academy Medical science of Ukraine"	Kiev
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	University Hospitals Bristol NHS Foundation Trust	Bristol
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Barts Health NHS Trust - St Bartholomew's Hospital	London
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	James Cook Uni Hospital	Middlesborough
United Kingdom	Royal Preston Hosptial	Preston
United Kingdom	Southampton General Hospital	Southampton
United States	University Of Michigan	Ann Arbor	Michigan
United States	University Of Colorado	Aurora	Colorado
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	MSK @Basking Ridge	Basking Ridge	New Jersey
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Inst.	Boston	Massachusetts
United States	Massachusetts General Hospital.	Boston	Massachusetts
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University Feinberg School Of Medicine	Chicago	Illinois
United States	University of Chicago; Hematology/Oncology	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Fairview Hospital; Cleveland Clinic Cancer Center	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Memorial Sloan-Kettering Cancer Center	Commack	New York
United States	University of Texas Southwestern	Dallas	Texas
United States	The Urology Center of Colorado	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Duke Cancer Center	Durham	North Carolina
United States	Baylor College of Medicine; Gastroenterology	Houston	Texas
United States	University of Iowa Hospital & Clinic; Division of Hematology/Oncology	Iowa City	Iowa
United States	Albert B. Chandler Medical Center; University of Kentucky	Lexington	Kentucky
United States	Saint Barnabas Medical Center Cancer Center	Livingston	New Jersey
United States	UCLA	Los Angeles	California
United States	USC Norris Cancer Center	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Yale Cancer Center; Medical Oncology	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Laura and ISAAC Perlmutter Cancer Center at NYU Langone.	New York	New York
United States	Stanford University Medical Center	Palo Alto	California
United States	Abramson Cancer Center; Univ of Pennsylvania	Philadelphia	Pennsylvania
United States	Fox Chase-Temple Cancer Center	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Miriam Hospital	Providence	Rhode Island
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Cleveland CL N Coast Cancer Cr	Sandusky	Ohio
United States	HonorHealth Research Institute - Pima - Virginia G. Piper Cancer Care Network	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Chesapeake Urology Research Associates	Towson	Maryland
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  China,  Czechia,  Finland,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Serbia,  Spain,  Switzerland,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-Free Survival (DFS), as Assessed by Investigator	DFS is defined as the time from randomization to the time of first occurrence of a DFS event. DFS events include: local (pelvic) recurrence of UC (including soft tissue and regional lymph nodes); urinary tract recurrence of UC (including all pathological stages and grades); distant metastasis of UC; or death from any cause. Tumor assessment will be performed using radiographic evaluations.	Randomization up to first occurrence of DFS event (up to approximately 50 months)
Secondary	Overall Survival (OS)	Overall survival is defined as the time from randomization to the date of death from any cause, regardless of whether the death occurs during study treatment or following treatment discontinuation.	Randomization until death due to any cause (up to approximately 80 months)
Secondary	Disease-Specific Survival (DSS), as Assessed by Investigator	DSS is defined as the time from randomization until the date of death from UC.	Randomization until death due to UC (up to approximately 50 months)
Secondary	Distant Metastasis-Free Survival (DMFS)	DMFS is defined as the time from randomization to the date of diagnosis of distant (that is, non-locoregional) metastases or death from any cause. Tumor assessment will be performed using radiographic evaluations.	Randomization up to diagnosis of distant metastases or death from any cause (up to approximately 50 months)
Secondary	Non-Urinary Tract Recurrence-Free Survival (NURFS)	NURFS is defined as the time from randomization to the time of first occurrence of a NURFS event. NURFS events include: local (pelvic) recurrence of UC (including soft tissue and regional lymph nodes); distant metastasis of UC; or death from any cause. Tumor assessment will be performed using radiographic evaluations.	Randomization up to time of first occurrence of a NURFS event (up to approximately 50 months)
Secondary	Percentage of Participants With Adverse Events (AEs)	Percentage of participants with at least one Adverse Event.	Screening up to approximately 80 months
Secondary	Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab	Percentage of participants with anti-therapeutic antibodies to atezolizumab.	Baseline up to approximately 50 months
Secondary	EuroQol 5-Dimension 5-Level (EQ-5D-5L) Visual Analogue Scale Score	The EQ-5D-5L is a generic preference-based HRQoL questionnaire that provides a single index value for health status and is used to inform pharmacoeconomic evaluations and to measure general health status. Visual analog scale (VAS) allows the patient to indicate, on a scale of 0-100, how his or her health is on the day of assessment, with 100 being the "best imaginable health state" and 0 being the "worst imaginable health state."	Day 1 of Cycle 1 up to approximately 50 months (Cycle length = 21 days)
Secondary	Minimum Observed Serum Atezolizumab Concentration (Cmin)	Minimum observed serum atezolizumab concentration (Cmin) prior to infusion on Day 1 of Cycles 1, 2, 3, and 4; every 8 cycles starting on Cycle 8; at treatment discontinuation; and at 120 days after the last dose of atezolizumab.	Pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, every 8 cycles from Cycle 8, at treatment discontinuation, 120 days after treatment discontinuation (up to approximately 50 months))(Cycle length = 21 days)
Secondary	Maximum Observed Serum Atezolizumab Concentration (Cmax)	Maximum observed serum atezolizumab concentration (Cmax) after infusion on Day 1 of Cycle 1.	Day 1 of Cycle 1 (Cycle length = 21 days)