Clinical trial • Phase III • Oncology

ATEZOLIZUMAB for Muscle-invasive bladder cancer

Phase III trial of ATEZOLIZUMAB for Muscle-invasive bladder cancer. Randomised, arm b (control arm): placebo iv infusion q4w on day 1 of each 28-day cycle.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Muscle-invasive bladder cancer
Trial Stage
Phase III
Drug Modality
Monoclonal antibody|Other

Key dates

Initial CTIS Submission Date
15-12-2023
First CTIS Authorization Date
07-02-2024

Trial design

Randomised, arm b (control arm): placebo iv infusion q4w on day 1 of each 28-day cycle Phase III trial in Belgium, Czechia, France and others.

Randomised
Yes
Comparator
Arm B (control arm): placebo IV infusion Q4W on Day 1 of each 28-day cycle
Biomarker Stratified
True, biomarker: ctDNA (circulating tumor DNA); strata: ctDNA-positive within 24 weeks of cystectomy (primary analysis population)
Target Sample Size
135
Trial Duration For Participant
365

Eligibility

Recruits 135 adults.

Inclusion criteria

  • {"criterion_text":"- 1. Histologically confirmed muscle-invasive urothelial carcinoma (MIUC) (also termed transitional cell carcinoma [TCC]) of the bladder. Patients with carcinomas showing mixed histologys are required to have a dominant transitional cell pattern\n- 2. TNM classification (based on American Joint Committee on Cancer [AJCC] Cancer Staging Manual, 8th Edition) at pathological examination of surgical resection. – Patients who received, or did not receive, platinum-based NAC with tumor stage of (y)pT2-4aN0M0 or (y)pT0-4aN+ M0. Patients who have received at least three cycles of a platinum containing regimen will be considered as having received prior NAC Patients who have not received platinum-based NAC must be ineligible (\"unfit\") for cisplatin-based adjuvant chemotherapy, have refused it, or will not receive it based on the treating physician’s decision. Cisplatin ineligibility is defined by any one of the following criteria: – Impaired renal function (glomerular filtration rate [GFR] < 60 mL/min); GFR should be assessed by direct measurement (i.e., creatinine clearance or ethyldediaminetetra-acetate) or, if not available, by calculation from serum/plasma creatinine (Cockcroft‑Gault formula) – A hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies – Grade 2 or greater peripheral neuropathy (i.e., sensory alteration or paresthesia including tingling) – ECOG Performance Status of 2\n- 3. Surgical resection of MIUC of the bladder\n- 4. Availability of a surgical tumor specimen that is suitable (adequate quality and quantity) for use in determining PD L1 expression, WES evaluable (ctDNA assay designability) report, and for exploratory biomarker research assessed by central laboratory testing.\n- 5. Submission of a post-surgery matched blood sample for the identification of somatic mutations in tumor tissue\n- 6. Submission of blood sample for plasma ctDNA testing, collected at least 6 weeks post-surgery"}

Exclusion criteria

  • {"criterion_text":"- 1. 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.\n- 2. 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\n- 3. Patients with active hepatitis B virus (HBV) 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\n- 4. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA\n- 5. Active tuberculosis confirmed by a test performed within 3 months prior to treatment initiation\n- 6. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 1.Investigator assessed DFS in patients who are ctDNA-positive within 24 weeks of cystectomy (primary analysis population)","definition_or_measurement_approach":"Investigator-assessed disease-free survival (DFS) in patients who are circulating-tumor DNA (ctDNA)-positive within 24 weeks of cystectomy (primary analysis population)."}

Secondary endpoints

  • {"endpoint_text":"- 1. OS in patients who are ctDNA-positive within 24 weeks after cystectomy (primary analysis population)","definition_or_measurement_approach":"Overall survival (OS) in patients ctDNA-positive within 24 weeks after cystectomy (primary analysis population)."}
  • {"endpoint_text":"- 2. Investigator-assessed DFS in in patients who are ctDNA-positive at any time following cystectomy (all-randomized population)","definition_or_measurement_approach":"Investigator-assessed DFS in patients ctDNA-positive at any time following cystectomy (all-randomized population)."}
  • {"endpoint_text":"- 3. IRF- assessed DFS in the primary analysis population","definition_or_measurement_approach":"Independent Review Facility (IRF)-assessed DFS in the primary analysis population."}
  • {"endpoint_text":"- 4. IRF- assessed DFS in all-randomized patients","definition_or_measurement_approach":"IRF-assessed DFS in all randomized patients."}
  • {"endpoint_text":"- 5. Investigator-assessed DSS in the primary analysis population","definition_or_measurement_approach":"Investigator-assessed disease-specific survival (DSS) in the primary analysis population."}
  • {"endpoint_text":"- 6. Investigator-assessed DMFS in the primary analysis population","definition_or_measurement_approach":"Investigator-assessed distant metastasis-free survival (DMFS) in the primary analysis population."}
  • {"endpoint_text":"- 7. Time to deterioration of function and QoL in the primary analysis population and in the all-randomized population","definition_or_measurement_approach":"Time-to-event assessment of deterioration in function and health-related quality of life (QoL) in primary and all-randomized populations."}
  • {"endpoint_text":"- 8. ctDNA clearance in the primary analysis population","definition_or_measurement_approach":"Assessment of ctDNA clearance in the primary analysis population."}
  • {"endpoint_text":"- 9. Incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)","definition_or_measurement_approach":"Incidence and severity graded by NCI CTCAE v5.0."}
  • {"endpoint_text":"- 10. Change from baseline in targeted vital signs","definition_or_measurement_approach":"Change from baseline in specified vital signs."}
  • {"endpoint_text":"- 11. Change from baseline in targeted clinical laboratory test results","definition_or_measurement_approach":"Change from baseline in specified clinical laboratory parameters."}
  • {"endpoint_text":"- 12. Serum concentration of atezolizumab at specified timepoints","definition_or_measurement_approach":"Pharmacokinetic measurement of serum atezolizumab concentrations at prespecified timepoints."}
  • {"endpoint_text":"- 13. Incidence of anti-drug antibodies (ADAs) to atezolizumab during the study","definition_or_measurement_approach":"Assessment of anti-drug antibody incidence during the study."}
  • {"endpoint_text":"- 14. Prevalence of ADAs to atezolizumab at baseline","definition_or_measurement_approach":"Baseline prevalence of anti-drug antibodies to atezolizumab."}

Recruitment

Registry Or Advocacy Recruitment
True, Centre Jean Perrin
Planned Sample Size
135
Recruitment Window Months
74
Consent Approach
Informed consent is obtained from participants. Subject information and informed consent form (L1_SIS and ICF) documents are provided in multiple languages (English, French, Spanish, Italian, Greek, Czech, German, Dutch). No specific assent process is described in the available records.

Geography

Total Number Of Sites
62
Total Number Of Participants
112

Belgium

Earliest CTIS Part Ii Submission Date
11-01-2024
Latest Decision Or Authorization Date
14-04-2026
Processing Time Days
824
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Algemeen Ziekenhuis Klina
Department Name
Medical Oncology
Contact Person Name
Wim Demey
Contact Person Email
wim.demey@klina.be
Site Name
Universitair Ziekenhuis Gent
Department Name
Medical oncology
Contact Person Name
Sylvie Rottey
Contact Person Email
studiesmedonc@uzgent.be

Czechia

Earliest CTIS Part Ii Submission Date
11-01-2024
Latest Decision Or Authorization Date
14-04-2026
Processing Time Days
824
Number Of Sites
3
Number Of Participants
5

Sites

Site Name
University Hospital Olomouc
Department Name
Onkologická klinika
Contact Person Name
Bohuslav Melichar
Contact Person Email
bohuslav.melichar@fnol.cz
Site Name
Fakultni Nemocnice V Motole
Department Name
Onkologická klinika 2. LF UK a FN Motol
Contact Person Name
Antonín Brisuda
Contact Person Email
antonin.brisuda@fnmotol.cz
Site Name
Fakultni Thomayerova nemocnice
Department Name
Onkologická klinika 1. LF UK a FTN
Contact Person Name
Michaela Matoušková
Contact Person Email
michaela.matouskova1@ftn.cz

France

Earliest CTIS Part Ii Submission Date
05-02-2024
Latest Decision Or Authorization Date
14-04-2026
Processing Time Days
799
Number Of Sites
13
Number Of Participants
13

Sites

Site Name
Institut Gustave Roussy
Department Name
Cancérologie
Contact Person Name
Yohann LORIOT
Contact Person Email
Yohann.loriot@gustaveroussy.fr
Site Name
Institut Universitaire Du Cancer Toulouse-Oncopole
Department Name
Cancérologie
Contact Person Name
Damien POUESSEL
Site Name
Institut Sainte Catherine
Department Name
Recherche clinique, cancerologie
Contact Person Name
Bertrand BILLEMONT
Contact Person Email
b.billemont@isc84.org
Site Name
Centre Leon Berard
Department Name
Cancérologie
Contact Person Name
Aude FLECHON
Contact Person Email
aude.flechon@lyon.unicancer.fr
Site Name
Centre Jean Perrin
Department Name
Cancérologie
Contact Person Name
Hakim MAHAMMEDI
Site Name
Institut De Cancerologie De L Ouest
Department Name
Oncologie médicale
Contact Person Name
Rémy DELVA
Contact Person Email
remy.delva@ico.unicancer.fr
Site Name
Immobiliere De Nancy
Department Name
Cancérologie
Contact Person Name
Raafet AFFI
Contact Person Email
r.affi@ilcgroupe.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Cancérologie
Contact Person Name
Marine GROSS-GOUPIL
Site Name
Hospital Foch
Department Name
Cancérologie
Contact Person Name
Christine ABRAHAM
Contact Person Email
c.abraham@hopital-foch.com
Site Name
Institut Mutualiste Montsouris
Department Name
Cancérologie
Contact Person Name
Emilie SOULARUE
Contact Person Email
emilie.soularue@imm.fr
Site Name
Centre Antoine Lacassagne
Department Name
Cancérologie
Contact Person Name
Delphine BORCHIELLINI
Site Name
Centre Leon Berard (duplicate entry if any)
Department Name
Cancérologie
Site Name
Institut Gustave Roussy (duplicate entry if any)
Department Name
Cancérologie

Germany

Earliest CTIS Part Ii Submission Date
11-01-2024
Latest Decision Or Authorization Date
17-04-2026
Processing Time Days
827
Number Of Sites
6
Number Of Participants
6

Sites

Site Name
Universitätsklinikum der Ruhr-Universität Bochum
Department Name
Marien-Hospital Herne, Urologische Klinik
Contact Person Name
Florian Roghmann
Site Name
Universitaetsklinikum Duesseldorf AöR
Department Name
Urologische Klinik
Contact Person Name
Günter Niegisch
Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
Klinik und Poliklinik für Urologie und Kinderurologie
Contact Person Name
Hubert Kübler
Contact Person Email
Kuebler_h@ukw.de
Site Name
Martha-Maria Krankenhaus Halle-Doelau gGmbH
Department Name
Klinik für Urologie
Contact Person Name
Florian Seseke
Contact Person Email
Florian.Seseke@Martha-Maria.de
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Klinik für Urologie
Contact Person Name
Friedemann Zengerling
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Klinik für Urologie
Contact Person Name
Steffen Rausch

Ireland

Earliest CTIS Part Ii Submission Date
11-01-2024
Latest Decision Or Authorization Date
14-04-2026
Processing Time Days
824
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
Tallaght University Hospital
Department Name
Oncology/Haematology Clinical Trials
Contact Person Name
Ray McDermott
Contact Person Email
ray.mcdermott@tuh.ie
Site Name
Cork University Hospital
Department Name
Cancer Trials Cork
Contact Person Name
Richard Bambury
Contact Person Email
uccctg@ucc.ie

Italy

Earliest CTIS Part Ii Submission Date
11-01-2024
Latest Decision Or Authorization Date
15-04-2026
Processing Time Days
825
Number Of Sites
13
Number Of Participants
25

Sites

Site Name
Istituto Oncologico Veneto
Department Name
Oncology
Contact Person Name
Marco Maruzzo
Contact Person Email
marco.maruzzo@iov.veneto.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
Oncology
Contact Person Name
Francesco Massari
Contact Person Email
francesco.massari@aosp.bo.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
Oncology
Contact Person Name
Andrea Necchi
Contact Person Email
necchi.andrea@hsr.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Oncology
Contact Person Name
Emilio Francesco Giunta
Contact Person Email
emilio.giunta@irst.emr.it
Site Name
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Department Name
Oncology
Contact Person Name
Consuelo Buttigliero
Contact Person Email
consuelo.buttigliero@gmail.com
Site Name
Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
Department Name
Oncology
Contact Person Name
Ferdinando Riccardi
Contact Person Email
nando.riccardi@gmail.com
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
Oncology
Contact Person Name
Giuseppe Fornarini
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Oncology
Contact Person Name
patrizia giannatempo
Site Name
Azienda USL Toscana Sud Est
Department Name
Oncology
Contact Person Name
Alketa Hamzaj
Site Name
Azienda Ospedaliera S Maria Di Terni
Department Name
Oncology
Contact Person Name
Annalisa Guida
Contact Person Email
a.guida@aospterni.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Oncology
Contact Person Name
Giampaolo Tortora
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
Oncology
Contact Person Name
Rosa Tambaro
Contact Person Email
r.tambaro@istitutotumori.na.it
Site Name
European Institute Of Oncology S.r.l.
Department Name
Oncology
Contact Person Name
Franco Nolè
Contact Person Email
franco.nole@ieo.it

Poland

Earliest CTIS Part Ii Submission Date
11-01-2024
Latest Decision Or Authorization Date
20-04-2026
Processing Time Days
830
Number Of Sites
3
Number Of Participants
8

Sites

Site Name
Szpital Grochowski Im.Dr Med. Rafała Masztaka Sp. z o.o.
Department Name
Oddział Chemioterapii
Contact Person Name
Iwona Skoneczna
Contact Person Email
iskoneczna@grochowski.waw.pl
Site Name
Dolnoslaskie Centrum Onkologii Pulmonologii I Hematologii
Department Name
Oddział Chirurgii Onkologicznej II
Contact Person Name
Łukasz Dołowy
Contact Person Email
lukasz.dolowy@dcopih.pl
Site Name
Uniwersytecki Szpital Kliniczny W Poznaniu
Department Name
Oddział Chemioterapii
Contact Person Name
Piotr Tomczak
Contact Person Email
piotr.tomczak@usk.poznan.pl

Spain

Earliest CTIS Part Ii Submission Date
11-01-2024
Latest Decision Or Authorization Date
16-04-2026
Processing Time Days
826
Number Of Sites
15
Number Of Participants
32

Sites

Site Name
Hospital Universitario Donostia
Department Name
Servicio de Oncología Médica
Contact Person Name
Naiara Sagastibelza Mariñelarena
Site Name
Hospital Universitario La Paz
Department Name
Servicio de Oncología
Contact Person Name
Alvaro Pinto Marín
Contact Person Email
alvaropintomarin@gmail.com
Site Name
Hospital Clinico San Carlos
Department Name
Servicio de Oncología
Contact Person Name
Javier Puente Vázquez
Contact Person Email
javierpuente.hcsc@gmail.com
Site Name
Hospital Universitario Reina Sofia
Department Name
Servicio de Oncología
Contact Person Name
Maria José Méndez Vidal
Site Name
Hospital Universitario Marques De Valdecilla
Department Name
Servicio de Oncología
Contact Person Name
Ignacio Durán Martínez
Contact Person Email
ignacioduranmartinez@gmail.com
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Servicio de Oncología
Contact Person Name
Begoña Pérez Valderrama
Contact Person Email
bpvalderrama@gmail.com
Site Name
Fundacion Instituto Valenciano De Oncologia
Department Name
Oncología Médica
Contact Person Name
Miguel Ángel Climent Durán
Contact Person Email
macliment@fivo.org
Site Name
Hospital Universitari Vall D Hebron
Department Name
Servicio de Oncología
Contact Person Name
Rafael Morales Barreda
Contact Person Email
rmorales@vhio.net
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Servicio de Oncología
Contact Person Name
Pablo Gajate Borau
Contact Person Email
gajateborau@gmail.com
Site Name
Hospital Clinic De Barcelona
Department Name
Servicio de Oncología
Contact Person Name
Oscar Reig Torras
Contact Person Email
oreig@clinic.cat
Site Name
Hospital Universitario 12 De Octubre
Department Name
Servicio de Oncología
Contact Person Name
Daniel Castellano
Contact Person Email
cdanicas@hotmail.com
Site Name
Parc Tauli Hospital Universitari
Department Name
Servicio de Oncología
Contact Person Name
Teresa Bonfill Abella
Contact Person Email
tbonfill@tauli.cat
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Servicio de Oncología
Contact Person Name
Isabel Chirivella González
Contact Person Email
chirivella_isa@gva.es
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Servicio de Oncología
Contact Person Name
Georgia Anguera Palacios
Contact Person Email
ganguera@santpau.cat
Site Name
Complejo Hospitalario Universitario Insular Materno Infantil
Department Name
Servicio de Oncología
Contact Person Name
Alfonso Gómez de Liaño Lista
Contact Person Email
Agomezdeliano84@gmail.com

Greece

Earliest CTIS Part Ii Submission Date
11-01-2024
Latest Decision Or Authorization Date
17-04-2026
Processing Time Days
827
Number Of Sites
5
Number Of Participants
14

Sites

Site Name
General University Hospital Of Larissa
Department Name
Department of Medical Oncology
Contact Person Name
Athanasios Kotsakis
Contact Person Email
thankotsakis@uth.gr
Site Name
Alexandra Hospital
Department Name
Clinical Therapeutics Department / Oncology Unit
Contact Person Name
Flora Zagouri
Contact Person Email
florazagouri@yahoo.co.uk
Site Name
General University Hospital Of Patras
Department Name
Division of Oncology, Department of Medicine
Contact Person Name
Angelos Koutras
Contact Person Email
angkoutr@otenet.gr
Site Name
Theageneio Cancer Hospital
Department Name
Oncology Clinic
Contact Person Name
Grigorios Rallis
Contact Person Email
grrallis@yahoo.com
Site Name
University General Hospital Attikon
Department Name
B' Propaedeutic Clinic of Internal Medicine
Contact Person Name
Aristotelis Bamias
Contact Person Email
abamias@med.uoa.gr

Sponsor

Primary sponsor

Full Name
F. Hoffmann-La Roche AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
IQVIA Limited
Responsibilities
Global CRO, Monitoring
Name
Icon Development Solutions LLC

Third parties

  • {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Drug Management, Randomization","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Covance Central Laboratory Services Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Global CRO, Monitoring","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Icon Development Solutions LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Other Third Party Duty","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
Tecentriq 840 mg concentrate for solution for infusion
Active Substance
ATEZOLIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
Marketing authorisation: EU/1/17/1220/002
Starting Dose
1680 mg
Dose Levels
1680 mg
Frequency
Q4W on Day 1 of each 28-day cycle
Maximum Dose
1680 mg
Investigational Product Name
Tecentriq concentrate for solution for infusion placebo 0mg
Modality
Other
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Frequency
Q4W on Day 1 of each 28-day cycle

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