Clinical trial NCT04919512: A Study of TAR-200 in Combination With Cetrelimab and Cetrelimab Alone in Participants With Muscle-Invasive Urothelial Carcinoma of the Bladder
Official title: A Phase 2, Open-Label, Multi-Center, Randomized Study of TAR-200 in Combination With Cetrelimab and Cetrelimab Alone in Participants With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Scheduled for Radical Cystectomy and Are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Urinary Bladder Neoplasms
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-06-09
Enrollment: 163
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the anti-tumor effects of TAR-200 in combination with intravenous (IV) cetrelimab and IV cetrelimab alone.

Detailed description: Bladder cancer is the tenth most common malignancy worldwide. Approximately 25 percent (%) of all new bladder cancer participants present with muscle invasive bladder cancer (MIBC) at the time of diagnosis, and roughly 50% will ultimately develop distant metastases. The TAR-200/ gemcitabine (JNJ-17000139) product is an intravesical drug delivery system regulated as an investigational drug. The drug constituent consists of gemcitabine minitablets and osmotic minitablets. Cetrelimab (JNJ-63723283) is a fully human immunoglobulin G4 (IgG4) kappa monoclonal antibody (mAb) that binds programmed-cell death protein (PD)-1. The standard of care in MIBC includes radical cystectomy (RC) with urinary diversion and is considered the preferred treatment option for participants who are considered surgical candidates. Study consists of a Screening phase, Treatment phase and follow-up phase. The total duration of study will be up to 2 years and 6 months. Efficacy, safety, pharmacokinetics (PK), and biomarkers will be assessed at specific time points during this study.

Eligibility criteria: Inclusion Criteria:

* Histologically proven, cT2-T4a N0, M0 infiltrating urothelial carcinoma of the bladder. Initial diagnosis must have been within 120 days of randomization date. Participants with variant histologic subtypes are allowed if tumor(s) demonstrate urothelial predominance. However, the presence of small cell or neuroendocrine variants will make a participant ineligible
* Participants with no residual tumor, or intravesical tumor size of less than or equal to (\<=)3 centimeter (cm) following transurethral resection of bladder tumor (TURBT) are eligible; debulking TURBT for any residual disease is encouraged but not mandated. Participants with persistent tumors greater than (\>)3 cm at screening must undergo a second debulking, re-staging TURBT. Participants will be ineligible if any individual tumor is \>3 cm after debulking TURBT
* Deemed eligible for and willing to undergo RC by the operating urologist
* Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 or 1
* Thyroid function tests within normal range or stable on hormone supplementation per investigator assessment. Investigators may consult an endocrinologist for participant eligibility assessment in the case of equivocal or marginal tests results
* All adverse events associated with any prior surgery must have resolved to common terminology criteria for adverse events (CTCAE) version 5.0 Grade less than (\<) 2 prior to randomization

Exclusion Criteria:

* Must not have received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment
* Participants must not have evidence of cT4b, or N1-3, or M1 disease based on central radiology staging (chest, abdomen, and pelvis must be performed using computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) within 42 days prior to randomization
* Presence of any bladder or urethral anatomic feature that, in the opinion of the Investigator, may prevent the safe placement, indwelling use, or removal of TAR-200
* Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time
* Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to enrollment
* Participants with evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has resolved prior to dosing

Primary outcomes:
measure: Percentage of Participants with Pathologic Complete Response (pCR)
timeFrame: Up to Week 15
Secondary outcomes:
measure: Recurrence-Free Survival (RFS)
timeFrame: Up to Week 108
measure: Number of Participants with Adverse Events (AEs) by Grades According to Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: Up to Week 108
measure: Number of Participants with Change from Baseline in Laboratory Abnormalities
timeFrame: Up to Week 108
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Urological Associates of Southern Arizona, P.C.
state: Arizona
city: Little Rock
country: United States
facility: UAMS Winthrop P. Rockefeller Cancer Institute
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Urology
state: Arkansas
city: Duarte
country: United States
facility: City of Hope
state: California
city: San Diego
country: United States
facility: Genesis Research
state: California
city: Golden
country: United States
facility: Colorodo Urology- St. Anthony Hospital
state: Colorado
city: Jacksonville
country: United States
facility: University of Florida Health Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute Emory University
state: Georgia
city: Lisle
country: United States
facility: DuPage Medical Group
state: Illinois
city: Indianapolis
country: United States
facility: Urology of Indiana
state: Indiana
city: Jeffersonville
country: United States
facility: First Urology
state: Indiana
city: Louisville
country: United States
facility: University of Louisville - James Graham Brown Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: University Of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Penn Medicine - PerelmanCenter for Advanced Medicine
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Troy
country: United States
facility: Michigan Institute of Urology, PC
state: Michigan
city: Minneapolis
country: United States
facility: University Of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School Of Medicine - Center For Advanced Medicine (CAM)
state: Missouri
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center
state: Missouri
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: Astoria
country: United States
facility: Mount Sinai Queens Infusion Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Bala-Cynwyd
country: United States
facility: MidLantic Urology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University Of Pittsburgh Medical Center UPMC Hillman Cancer Center
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates
state: Tennessee
city: Houston
country: United States
facility: Houston Metro Urology
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio Research
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: University of Washington School of Medicine
state: Washington
city: Brugge
country: Belgium
facility: AZ Sint Jan Brugge Oostende AV
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis Sint-Jan
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
city: Haine Saint Paul La Louviere
country: Belgium
facility: Hopital de Jolimont
city: Merksem
country: Belgium
facility: ZNA Jan Palfijn
city: Mons
country: Belgium
facility: Centre Interuniversitaire Ambroise Pare - Ambroise Paré
city: Bordeaux
country: France
facility: Clinique Tivoli Ducos
city: Brest
country: France
facility: ICH Hopital A. Morvan
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Lille
country: France
facility: Hôpital Privé Le Bois
city: Limoges
country: France
facility: Polyclinique de Limoges - Francois Chenieux
city: Marseille
country: France
facility: Hopital de la Timone
city: Montpellier
country: France
facility: CHU Montpellier
city: Nimes
country: France
facility: CHU Nimes
city: Paris Cedex 18
country: France
facility: Hopital Bichat Claude Bernard
city: Paris
country: France
facility: Hopital Europeen Georges-Pompidou
city: Pierre Bénite
country: France
facility: Hospices Civils de Lyon HCL
city: Quint-Fonsegrives
country: France
facility: Clinical La Croix Du Sud - Ramsay Santé
city: Toulon
country: France
facility: HIA se Sainte-Anne - Toulon
city: Toulouse
country: France
facility: Clinique Pasteur
city: Berlin-Kreuzberg
country: Germany
facility: Vivantes Klinikum Am Urban
city: Braunschweig
country: Germany
facility: Staedtisches Klinikum Braunschweig
city: Frankfurt am Main
country: Germany
facility: Agaplesion Frankfurter Diakonie Kliniken GmbH, Markus Krankenhaus
city: Halle Saale
country: Germany
facility: Universitaetsklinikum Halle Saale
city: Herne
country: Germany
facility: Marien hospital Herne
city: Muenster
country: Germany
facility: Universitatsklinikum Munster
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center - Hasharon Hospital
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Tel Aviv Yafo
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Avellino
country: Italy
facility: Ospedale San Giuseppe Moscati di Avellino
city: Carpi
country: Italy
facility: Ospedale Civile Ramazzini
city: Genova
country: Italy
facility: SPDC Villa Scassi
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Milano
country: Italy
facility: Istituto Dei Tumori Di Milano
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Pozzuoli
country: Italy
facility: ASL Napoli 2 Nord-SM delle Grazie Hospital
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
city: Rozzano
country: Italy
facility: IRCCS Istituto Clinico Humanitas
city: Torino
country: Italy
facility: Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Gangnam Gu
country: Korea, Republic of
facility: Samsung Medical Center
city: Goyang-Si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Mary s Hospital
city: Yangsan-si
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Almelo
country: Netherlands
facility: Ziekenhuisgroep Twente
city: Den Haag
country: Netherlands
facility: Haga ziekenhuis
city: Nijmegen
country: Netherlands
facility: Radboud Umcn
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis
city: A Coruna
country: Spain
facility: Hosp Univ A Coruna
city: Barcelona
country: Spain
facility: Fund. Puigvert
city: Granada
country: Spain
facility: Hosp. Univ. San Cecilio
city: Madrid
country: Spain
facility: Clinica Univ. de Navarra
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: Hosp Virgen de La Victoria
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: Preston
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS Foundation Trust Royal Preston Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: