Clinical trial • Phase III • Oncology

DURVALUMAB for Non-muscle invasive bladder cancer

Phase III trial of DURVALUMAB for Non-muscle invasive bladder cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Non-muscle invasive bladder cancer
Trial Stage
Phase III
Drug Modality
Monoclonal antibody|Vaccine|Small molecule

Key dates

Initial CTIS Submission Date
30-01-2024
First CTIS Authorization Date
12-03-2024

Trial design

Randomised, open-label, arm 1 (durvalumab + bcg): durvalumab (1500 mg iv 13 cycles [q4w]) + bcg induction: 1 vial of tice® bcg (or approved equivalent local strain) intravesical weekly for 6 weeks; bcg maintenance: 1 vial intravesical for 3 weekly doses at 3, 6, 12, 18, and 24 months. for persistent cis at 3 months a single bcg re-induction weekly for 6 weeks followed by maintenance as described. arm 2 (durvalumab + bcg induction only): durvalumab (1500 mg iv 13 cycles [q4w]) + bcg induction only: 1 vial intravesical weekly for 6 weeks (re-induction for persistent cis allowed). arm 3 (bcg alone): bcg induction with 1 vial intravesical weekly for 6 weeks + bcg maintenance as per schedule (3 weekly doses at 3, 6, 12, 18, and 24 months).-controlled Phase III trial in Poland, Austria, Belgium and others.

Randomised
Yes
Open Label
Yes
Comparator
Arm 1 (Durvalumab + BCG): Durvalumab (1500 mg IV 13 cycles [q4w]) + BCG induction: 1 vial of TICE® BCG (or approved equivalent local strain) intravesical weekly for 6 weeks; BCG maintenance: 1 vial intravesical for 3 weekly doses at 3, 6, 12, 18, and 24 months. For persistent CIS at 3 months a single BCG re-induction weekly for 6 weeks followed by maintenance as described. Arm 2 (Durvalumab + BCG induction only): Durvalumab (1500 mg IV 13 cycles [q4w]) + BCG induction only: 1 vial intravesical weekly for 6 weeks (re-induction for persistent CIS allowed). Arm 3 (BCG alone): BCG induction with 1 vial intravesical weekly for 6 weeks + BCG maintenance as per schedule (3 weekly doses at 3, 6, 12, 18, and 24 months).
Target Sample Size
560

Eligibility

Recruits 560 isVulnerablePopulationSelected: true. Subject information and informed consent forms for adults are provided (multiple language versions listed). No information on assent or parental consent for minors is provided in the available data..

Vulnerable Population
isVulnerablePopulationSelected: true. Subject information and informed consent forms for adults are provided (multiple language versions listed). No information on assent or parental consent for minors is provided in the available data.

Inclusion criteria

  • {"criterion_text":"-BCG-naïve (patients who have not received priorintravesical BCG or who previously received but stoppedBCG more than 3 years before study entry are eligible). - Local histological confirmation (based on pathologyreport) of high-risk transitional cell carcinoma of theurothelium of the urinary bladder confined to the mucosaor submucosa.A high-risk tumor is defined as one of thefollowing: -T1 tumor -High grade/G3 tumor -CIS -Multiple andrecurrent and large (with diameter of largesttumor ≥3cm) tumors (all conditions must be met in this point) -Complete resection of all Ta/T1 papillary disease prior torandomization, with the TURBT removing high-risk NMIBCperformed not more than 4 months before randomizationin the study. Patients with residual CIS after TURBT are eligible. -No prior radiotherapy for bladder cancer. -No prior exposure to immune-mediated therapy of cancerincluding, but not limited to, other anti CTLA-4, anti-PD-1,anti-PD-L1, and anti-programmed cell death ligand 2antibodies. Patients who have been treated with anticancer vaccines will be excluded."}

Exclusion criteria

  • {"criterion_text":"-Evidence of muscle-invasive, locally advanced,metastatic, and/or extra vesical bladder cancer (ie, T2,T3, T4, and / or stage IV).\n-Concurrent extravesical (ie, urethra, ureter, or renalpelvis), non-muscle-invasive transitional cell carcinoma of the urothelium.\n-Previous investigational product (IP) assignment in the present study.\n-Any concurrent chemotherapy, IP, biologic, or hormonaltherapy for cancer treatment. Concurrent use of hormonaltherapy for noncancer related conditions (eg, hormonereplacement therapy) is acceptable. Chemotherapy for previous instances of NMIBC is acceptable. Patients who have received a single instillation of Mitomycin C or equivalent chemotherapy agent immediately after TURBT can be enrolled in the study.\n-Active infection including TB, hepatitis B (known positivehepatitis B virus [HBV] surface antigen [HBsAg] result),hepatitis C virus (HCV), or human immunodeficiency virus(HIV [positive HIV] 1/2) antibodies. Patients with a pastor resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) areeligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). Appropriate TB tests (e.g.skin or interferon gamma tests) should be performed to exclude TB infection requiring treatment. Additional clinical evaluations including clinical history, physical examination, radiographic findings, and other diagnostic procedures and specialist consultations should be performed if necessary.\n-Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroidinjections (eg, intra articular injection) Systemic corticosteroids at physiologic doses not toexceed 10 mg/day of prednisone or its equivalent Steroids as premedication for hypersensitivity reactions(eg, computed tomography [CT] scan premedication)\n-Active or prior documented autoimmune or inflammatorydisorders (including inflammatory bowel disease [eg,colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegenersyndrome [granulomatosis with polyangiitis, Graves’disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: Patients with vitiligo or alopecia Patients with hypothyroidism (e.g., following Hashimotosyndrome) stable on hormone replacement. Any chronic skin condition that does not requiresystemic therapy Patients without active disease in the last 5 years maybe included but only after consultation with the Study Physician − Patients with celiac disease controlled by diet alone − History of another primary malignancy except for Malignancy treated with curative intent and with noknown active disease ≥ 2 years before the first dose of IPand of low potential risk for recurrence during study period Adequately treated nonmelanoma skin cancer or lentigomaligna without evidence of disease Adequately treated CIS without evidence of disease Prostate cancer (tumor/node/metastasis stage) of stage≤ T2cN0M0 without biochemical recurrence or progression that in the opinion of the Investigator does not require active intervention."}

Endpoints

Primary endpoints

  • {"endpoint_text":"-Disease-free survival (DFS)","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"-Disease free at 24 months (DFS24)\n-Survival at 5 years (OS5)\n-Complete response rate (CRR)\n-Any disease-free survival (aDFS)\n-Time to muscle-invasive bladder (MIBC) cancer ormetastasis\n-Time to cystectomy\n-Time to development of upper track urothelial carcinoma(UTUC)\n-Disease related symptoms\n-Patient reported treatment tolerability\n-Assessment of PK of Durvalumab\n-Immunogenicity of Durvalumab (ADA) in combination with BCG","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
560
Recruitment Window Months
20
Consent Approach
Informed consent obtained using subject information sheets and informed consent forms for adults; multiple language versions and addenda listed (e.g., Polish, English, Dutch, French, German, Spanish). Consent provided by adult participants; no information provided on assent or parental consent for minors in the available documents.

Geography

Total Number Of Sites
62
Total Number Of Participants
466

Poland

Earliest CTIS Part Ii Submission Date
21-02-2024
Latest Decision Or Authorization Date
25-03-2024
Processing Time Days
33
Number Of Sites
10
Number Of Participants
133

Sites

Site Name
Regionalny Szpital Specjalistyczny Im. Dr. Wladyslawa Bieganskiego
Department Name
Oddział Onkologii Klinicznej
Contact Person Name
Urszula Sadowska
Contact Person Email
ula@stolcad.pl
Site Name
Dolnoslaskie Centrum Onkologii Pulmonologii I Hematologii
Department Name
Oddział Chirurgii Onkologicznej II Urologia
Contact Person Name
Krzysztof Tupikowski
Contact Person Email
tupikowski.k@dco.com.pl
Site Name
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
Department Name
Klinika Urologii Ogólnej, Onkologicznej i Czynnosciowej
Contact Person Name
Piotr Radziszewski
Contact Person Email
pradziszewski@wum.edu.pl
Site Name
Provita Profamilia
Department Name
NZOZ Profamilia Provita
Contact Person Name
Michal Maslowski
Contact Person Email
m.maslowski@provitacm.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie-Panstwowy Instytut Badawczy
Department Name
Centrum Onkologii
Contact Person Name
Tomasz Demkow
Contact Person Email
demkow@coi.waw.pl
Site Name
Uniwersytecki Szpital Kliniczny Im Jana Mikulicza Radeckiego We Wroclawiu
Department Name
Klinika Urologii i Onkologii Urologicznej
Contact Person Name
Romuald Zdrojowy
Contact Person Email
romuald.zdrojowy@umw.edu.pl
Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Klinika Onkologii i Radioterapii
Contact Person Name
Renata Zaucha
Contact Person Email
pradziszewski@wum.edu.pl
Site Name
Szpital Wojewodzki Im. Mikolaja Kopernika W Koszalinie
Department Name
Oddział Dzienny Chemioterapii
Contact Person Name
Mariusz Kwiatkowski
Contact Person Email
mariusz.kwiatkowski@swk.med.pl
Site Name
Clinical Research Center Sp. z o.o. Medic-R sp.k.
Department Name
Clinical Research Center Sp. z o. o. MEDIC-R Sp.K.
Contact Person Name
Michal Krawczynski
Site Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Zespolony im. Jędrzeja Sniadeckieg
Department Name
Oddział Urologii Onkologicznej i Ogólnej
Contact Person Name
Robert Kozlowski
Contact Person Email
rkozlowski12@gmail.com

Austria

Earliest CTIS Part Ii Submission Date
21-02-2024
Latest Decision Or Authorization Date
18-03-2024
Processing Time Days
26
Number Of Sites
5
Number Of Participants
25

Sites

Site Name
Gemeinnutzige Salzburger Landes kliniken Betriebsgesellschaft mbH
Department Name
Universitätsklinikum für Urologie und Andrologie der PMU
Contact Person Name
Lukas Lusuardi
Contact Person Email
l.lusuardi@salk.at
Site Name
Medizinische Universitaet Innsbruck
Department Name
Universitätsklinik für Urologie
Contact Person Name
Wolfgang Horninger
Site Name
Ordensklinikum Linz GmbH
Department Name
Abteilung für Urologie und Andrologie
Contact Person Name
Ferdinand Luger
Site Name
Medical University Of Vienna
Department Name
AKH-Universitätsklinik für Urologie
Contact Person Name
Kilian Gust
Contact Person Email
kilian.gust@meduniwien.ac.at
Site Name
University Hospital Graz
Department Name
Universitätsklinik für Urologie
Contact Person Name
Sascha Ahyai
Contact Person Email
sascha.ahyai@medunigraz.at

Belgium

Earliest CTIS Part Ii Submission Date
21-02-2024
Latest Decision Or Authorization Date
19-03-2024
Processing Time Days
27
Number Of Sites
4
Number Of Participants
32

Sites

Site Name
Hopital Erasme
Department Name
Urology
Contact Person Name
Thierry Roumeguère
Site Name
Algemeen Ziekenhuis Delta
Department Name
Urology
Contact Person Name
Lieven Goeman
Contact Person Email
ctc.uro@azdelta.be
Site Name
Az Maria Middelares Gent
Department Name
Urology
Contact Person Name
Filip Ameye
Site Name
UZ Leuven
Department Name
Urology
Contact Person Name
Steven Joniau
Contact Person Email
urologie.trial@uzleuven.be

Germany

Earliest CTIS Part Ii Submission Date
21-02-2024
Latest Decision Or Authorization Date
15-03-2024
Processing Time Days
23
Number Of Sites
14
Number Of Participants
82

Sites

Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Campus Charité Mitte Urologische Klinik
Contact Person Name
Maria de Santis
Site Name
Philipps-Universitaet Marburg
Department Name
Klinik für Urologie und Kinderurologie
Contact Person Name
Christian Keil
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Campus Großhadern Urologische Klinik
Contact Person Name
Jozefina Casuscelli
Site Name
Praxisklinik Urologie Rhein Ruhr
Department Name
Praxisklinik Urologie Rhein Ruhr
Contact Person Name
Elke Stagge
Contact Person Email
muelheim@pur-r.com
Site Name
MVZ - Urologie 24 GmbH
Department Name
MVZ - Urologie 24 GmbH
Contact Person Name
Bernd Schmitz-Dräger
Contact Person Email
urostudy@urologie24.de
Site Name
UZE Urologisches Zentrum Euregio Urologische Praxis am Wasserturm
Department Name
UZE Urologisches Zentrum Euregio Urologische Praxis am Wasserturm
Contact Person Name
Thomas Pulte
Contact Person Email
Wuerselen@uro-euregio.info
Site Name
Urologie Neandertal
Department Name
Urologie Neandertal - Standort Mettmann
Contact Person Name
Philipp Spiegelhalder
Site Name
Urologische Gemeinschaftspraxis
Department Name
Urologische Gemeinschaftspraxis Wesel
Contact Person Name
Miguel Garcia Schürmann
Contact Person Email
mail@urologie-wesel.de
Site Name
Studienpraxis Urologie Susan Feyerabend MD Tilman Todenhoefer MD PhD GbR
Department Name
Studienpraxis Urologie
Contact Person Name
Susan Feyerabend
Contact Person Email
praxis@studienurologie.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Klinisches Studienzentrum Chirurgie (KSC) Chirurgische Universitaetsklinik Heidelberg
Contact Person Name
Viktoria Schütz
Contact Person Email
ksc@med.uni-heidelberg.de
Site Name
Urologie Bayenthal
Department Name
Urologie Bayenthal
Contact Person Name
Jörg Klier
Contact Person Email
praxis@urologie-bayenthal.de
Site Name
Universitaetsklinikum Muenster AöR
Department Name
Klinik für Urologie und Kinderurologie
Contact Person Name
Martin Bögemann
Contact Person Email
uroonkologie@ukmuenster.de
Site Name
Urologicum Duisburg
Department Name
Urologicum Duisburg
Contact Person Name
Eva Hellmis
Contact Person Email
praxis@urologicum-duisburg.de
Site Name
Medizinische Hochschule Hannover
Department Name
Klinik für Urologie und Urologische Onkologie
Contact Person Name
Christoph von Klot

Spain

Earliest CTIS Part Ii Submission Date
21-02-2024
Latest Decision Or Authorization Date
12-03-2024
Processing Time Days
20
Number Of Sites
18
Number Of Participants
144

Sites

Site Name
Hospital Universitario La Paz
Department Name
Urologia
Contact Person Name
Mario Alvarez Maestro
Contact Person Email
mario.alvarez@salud.madrid.org
Site Name
Hospital Universitario Quironsalud Madrid
Department Name
Oncologia
Contact Person Name
Elena Almagro Casado
Contact Person Email
elena.almagro@quironsalud.es
Site Name
Hospital Universitari Vall D Hebron
Department Name
Urologia
Contact Person Name
Carles Raventos Busquets
Contact Person Email
cravento@vhebron.net
Site Name
Fundacio Puigvert
Department Name
Urologia
Contact Person Name
Oscar Rodriguez Faba
Site Name
Hospital Universitario Infanta Cristina
Contact Person Name
Juan Ignacio Delgado Mingorance
Site Name
Clinica Universidad De Navarra
Department Name
Urologia
Contact Person Name
Marcos Torres Roca
Contact Person Email
mtroca@unav.es
Site Name
Hospital Universitario Central De Asturias
Department Name
Urologia
Contact Person Name
Miguel Hevia Suarez
Contact Person Email
miguel.hevia@sespa.es
Site Name
Parc Tauli Hospital Universitari
Department Name
Urologia
Contact Person Name
Naim Hannaoui Hadi
Contact Person Email
NHannaoui@tauli.cat
Site Name
Hospital Clinic De Barcelona
Department Name
Urologia
Contact Person Name
Antonio Alcaraz Asensio
Contact Person Email
AALCARAZ@clinic.cat
Site Name
Hospital Del Mar
Department Name
Urologia
Contact Person Name
Lluis Ceccchini Rosell
Contact Person Email
lcecchini@parcdesalutmar.cat
Site Name
Hospital Clinico San Carlos
Department Name
Oncologia
Contact Person Name
Javier Puente Vazquez
Contact Person Email
javier.puente@salud.madrid.org
Site Name
Hospital Universitario 12 De Octubre
Department Name
Urologia
Contact Person Name
Felix Guerrero Ramos
Site Name
Hospital Universitario Virgen De Valme
Department Name
Urologia
Contact Person Name
Francisco Javier Rico Lopez
Site Name
Hospital General Universitario De Elche
Department Name
Oncologia
Contact Person Name
Federico Jose Vazquez Mazon
Contact Person Email
oncologia_elx@gva.es
Site Name
Hospital Universitario Virgen De La Victoria
Department Name
Urologia
Contact Person Name
Bernardo Herrera Imbroda
Site Name
Hospital Universitario Virgen De La Macarena
Department Name
Urologia
Contact Person Name
Carlos González Caliz
Contact Person Email
carlosgcaliz88@gmail.com
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Oncologia
Contact Person Name
Cristina Caballero Diaz
Contact Person Email
caballero_cri@gva.es

France

Earliest CTIS Part Ii Submission Date
21-02-2024
Latest Decision Or Authorization Date
12-03-2024
Processing Time Days
20
Number Of Sites
8
Number Of Participants
42

Sites

Site Name
Hospices Civils De Lyon
Department Name
Service D'Urologie et Chirurgie de la Transplatation
Contact Person Name
Marc Colombel
Contact Person Email
marc.colombel@chu-lyon.fr
Site Name
Centre Hospitalier Universitaire Amiens Picardie
Department Name
Service Urologie et Transplatation
Contact Person Name
Fabien Saint
Contact Person Email
saint.fabien@chu-amiens.fr
Site Name
Centre Hospitalier Universitaire D Angers
Department Name
Service d'Urologie
Contact Person Name
Pierre Bigot
Contact Person Email
pibigot@chu-angers.fr
Site Name
Hospital Foch
Department Name
Service d'Urologie
Contact Person Name
Thierry Lebret
Contact Person Email
t.lebret@hopital-foch.com
Site Name
Hopital Europeen Marseille
Department Name
Service d'Urologie
Contact Person Name
Julien Deturmeny
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Service Oncologie Medicale
Contact Person Name
Delphine Topart
Contact Person Email
d-topart@chu-montpellier.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Service d'Urologie, andrologie et transplantation rénale
Contact Person Name
Gregoire Robert
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Service Oncologie & Hematologie
Contact Person Name
Philippe Barthelemy

Netherlands

Earliest CTIS Part Ii Submission Date
21-02-2024
Latest Decision Or Authorization Date
13-03-2024
Processing Time Days
21
Number Of Sites
3
Number Of Participants
8

Sites

Site Name
Amphia Hospital
Department Name
Interne Geneeskunde
Contact Person Name
Hans Westgeest
Contact Person Email
secrint@amphia.nl
Site Name
Amsterdam UMC
Department Name
Urology
Principal Investigator Name
Jorg Reinier Oddens
Principal Investigator Email
urol@amsterdamumc.nl
Contact Person Email
g.dhaens@amsterdamumc.nl
Site Name
St. Antonius Ziekenhuis
Department Name
Interne Geneeskunde
Contact Person Name
Jarmo Hunting

Sponsor

Primary sponsor

Full Name
AstraZeneca AB
Organisation Type
Pharmaceutical company
Country Of Registered Address
Sweden

Investigational products

Investigational Product Name
IMFINZI 50 mg/mL concentrate for solution for infusion.
Active Substance
DURVALUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS
Route
Intravenous
Authorisation Status
Authorised
Starting Dose
1500 mg
Dose Levels
1500 mg
Frequency
q4w (every 4 weeks)
Maximum Dose
1500 mg
Investigational Product Name
DURVALUMAB
Active Substance
DURVALUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS
Route
Intravenous
Authorisation Status
Authorised
Starting Dose
1500 mg
Dose Levels
1500 mg
Frequency
q4w (every 4 weeks)
Maximum Dose
1500 mg
Investigational Product Name
OncoTICE® powder for instillation fluid for intravesical use containing 2-8 x 108 CFU Tice BCG.
Active Substance
BACILLUS CALMETTE-GUÉRIN (BCG), TICE
Modality
Vaccine
Routes Of Administration
INTRAVESICAL USE
Route
Intravesical
Authorisation Status
Authorised
Starting Dose
1 vial intravesical (TICE® BCG or approved local equivalent) weekly for 6 weeks (induction)
Frequency
Weekly for induction; maintenance 3 weekly doses at 3, 6, 12, 18, 24 months
Investigational Product Name
Placebo
Modality
Other
Investigational Product Name
MYCOPHENOLATE MOFETIL
Active Substance
MYCOPHENOLATE MOFETIL
Modality
Small molecule
Routes Of Administration
ORAL
Route
Oral
Authorisation Status
Authorised
Investigational Product Name
INFLIXIMAB
Active Substance
INFLIXIMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS INFUSION
Route
Intravenous infusion
Authorisation Status
Authorised
Combination Treatment
Yes

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