Clinical trial NCT04172675: A Study of Erdafitinib Versus Investigator Choice of Intravesical Chemotherapy in Participants Who Received Bacillus Calmette-Guérin (BCG) and Recurred With High Risk Non-Muscle-Invasive Bladder Cancer (NMIBC)
Official title: A Randomized Phase 2 Study of Erdafitinib Versus Investigator Choice of Intravesical Chemotherapy in Subjects Who Received Bacillus Calmette-Guérin (BCG) and Recurred With High Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) and FGFR Mutations or Fusions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urinary Bladder Neoplasms
Keywords: Non muscle invasive bladder cancer (NMIBC)
Bacillus calmette- guerin (BCG) failure
BCG unresponsive
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-11-21
Enrollment: 107
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 recurrence-free survival (RFS) in participants treated with erdafitinib vs Investigator's Choice, for participants with high-risk non-muscle-invasive bladder cancer (NMIBC) who harbor fibroblast growth factor receptor (FGFR) mutations or fusions, and who recurred after bacillus calmette-guerin (BCG) therapy.

Detailed description: This study enrolls participants with high risk NMIBC and FGFR mutations or fusions. Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) 1-4 inhibitor with demonstrated clinical activity in participants with solid tumors, including urothelial carcinoma, with alterations in the FGFR pathway. In Cohort 1, participants will be randomized to erdafitinib or to Investigators Choice (intravesical gemcitabine or intravesical mitomycin C \[MMC\] or hyperthermic MMC). The study consists of screening period, treatment phase, follow-up phase, and long-term extension phase.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed, recurrent, non-muscle-invasive urothelial carcinoma of the bladder. Variant pathology are allowed
* Tumor with specified fibroblast growth factor receptor (FGFR) mutations or fusions
* Bacillus Calmette- Guerin (BCG)-unresponsive after adequate BCG therapy or BCG experienced participants
* Refuses or is not eligible for cystectomy (Cohort 1 and Cohort 2 only)
* Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-1
* Must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
* A woman of childbearing potential must have a negative pregnancy test (beta-human chorionic gonadotropin \[beta-hCG\]) (urine or serum) within 7 days before randomization (Cohort 1) or the first dose of study drug (Cohort 2 and Cohort 3)
* Adequate bone marrow, liver, and renal function as specified in the protocol

Exclusion Criteria:

* Histologically confirmed, muscle-invasive (T2 or higher stage) urothelial carcinoma of the bladder
* Histopathology demonstrating any small cell component, pure adenocarcinoma, pure squamous cell carcinoma, or pure squamous CIS of the bladder
* Prior treatment with an FGFR inhibitor
* Active malignancies other than the disease being treated under study. The only allowed exceptions are: (a) skin cancer treated within the last 24 months that is considered completely cured (b) adequately treated lobular carcinoma in situ (LCIS) and ductal CIS (c) history of localized breast cancer and receiving antihormonal agents, or history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy
* Current central serous retinopathy or retinal pigment epithelial detachment of any grade

Primary outcomes:
measure: Recurrence-Free Survival (RFS)
timeFrame: Up to 4 years
Secondary outcomes:
measure: Time to Progression
timeFrame: Up to 4 years
measure: Overall Survival
timeFrame: Up to 4 years
measure: Recurrence-Free Survival
timeFrame: Months 6 and 12
measure: Plasma Concentration of Erdafitinib
timeFrame: Cycle 1 Day 14, Cycle 2 Day 1 (each cycle is of 28 days)
measure: Number of Participants with Adverse events
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Urological Associates of Southern Arizona, P.C.
state: Arizona
city: Los Angeles
country: United States
facility: USC Institute of Urology
state: California
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Hialeah
country: United States
facility: Urological Research Network
state: Florida
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Springfield
country: United States
facility: Simmons Cancer Institute
state: Illinois
city: Westwood
country: United States
facility: University of Kansas
state: Kansas
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Sanborn
country: United States
facility: Great Lakes Physician PC d/b/a Western New York Urology Associates
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Cincinnati
country: United States
facility: The Urology Group
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University- James Cancer Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health And Science University
state: Oregon
city: Bala-Cynwyd
country: United States
facility: MidLantic Urology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Cancer Centers
state: Pennsylvania
city: Nashville
country: United States
facility: Urology Associates
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Froedtert Hospital
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Sociedade Beneficente de Senhoras Hospital Sirio Libanes
city: Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: CEMIC Saavedra
city: Ciudad Autonoma de
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Cordoba
country: Argentina
facility: Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica
city: Cordoba
country: Argentina
facility: Centro Urologico Profesor Bengio
city: Cordoba
country: Argentina
facility: Hospital Privado de Cordoba
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Darlinghurst
country: Australia
facility: St Vincent s Hospital Sydney
city: Macquarie University
country: Australia
facility: Macquarie University
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liege
country: Belgium
facility: CHU Sart-Tilman
city: Roeselare
country: Belgium
facility: Algemeen Ziekenhuis Delta
city: Curitiba
country: Brazil
facility: Liga Paranaense de Combate ao Cancer
city: Fortaleza
country: Brazil
facility: Oncocentro Ceará
city: Goiania
country: Brazil
facility: Associacao de Combate ao Cancer em Goias - Hospital de Cancer Araujo Jorge
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Cancer
city: Porto Alegre
country: Brazil
facility: Irmandade Santa Casa de Misericordia de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao S A
city: Recife
country: Brazil
facility: Instituto de Medicina Integral Professor Fernando Figueira
city: Ribeirão Preto
country: Brazil
facility: Hospital Das Clinicas Da Faculdade De Medicina De RPUSP HCRP
city: Rio de Janeiro
country: Brazil
facility: Oncoclinicas Rio de Janeiro S A
city: Rio de Janeiro
country: Brazil
facility: Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
city: Santo Andre
country: Brazil
facility: CEPHO Centro de Estudos e Pesquisa de Hematologia e Oncologia
city: Sao Paulo
country: Brazil
facility: Fundacao Faculdade de Medicina Instituto do Cancer do Estado de Sao Paulo
city: Sao Paulo
country: Brazil
facility: Instituto de Assistencia Medica ao Servidor Publico Estadual IAMSPE
city: São Paulo
country: Brazil
facility: Sociedade Beneficente de Senhoras Hospital Sirio Libanes
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiaotong University School of Medicine
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Liberec
country: Czechia
facility: Krajská nemocnice Liberec
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Bordeaux
country: France
facility: Hopital Pellegrin CHU Bordeaux
city: Clermont Ferrand
country: France
facility: CHU Gabriel-Montpied
city: Lille
country: France
facility: Hopital Huriez
city: Lyon Cedex 03
country: France
facility: Hôpital Edouard Herriot
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
city: Paris
country: France
facility: Hôpital Universitaire Pitié-Salpêtrière
city: Paris
country: France
facility: Groupe Hospitalier Diaconesses Croix Saint Simon
city: Paris
country: France
facility: Hopital Bichat Claude Bernard
city: Poitiers
country: France
facility: CHU De Poitiers
city: Rennes Cedex
country: France
facility: Chu Rennes Hopital Pontchaillou
city: Rouen
country: France
facility: Hopital Charles Nicolle
city: Saint Gregoire
country: France
facility: CHP Saint Gregoire
city: Toulouse
country: France
facility: Institut Universitaire du Cancer Toulouse Oncopole
city: Vandœuvre-lès-Nancy Cedex
country: France
facility: Centre Hospitalier Universitaire de Nancy - Hôpital Central
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Duisburg
country: Germany
facility: Urologicum Duisburg
city: Herne
country: Germany
facility: Klinikum Herne - Urologie
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig Holstein Campus Lubeck
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar - III. Med. Klinik und Poliklinik
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Mülheim an der Ruhr
country: Germany
facility: Praxisklinik Urologie Rhein/Ruhr - Germany
city: Nuernberg
country: Germany
facility: MVZ Urologie 24 gGmbH
city: Nuertingen
country: Germany
facility: Studienpraxis Urologie Drs. Feyerabend
city: Wesseling
country: Germany
facility: CUROS - Uberörtliche urologische Gemeinschaftspraxis
city: Bangalore
country: India
facility: Health Care Global Enterprises pvt Ltd
city: Delhi
country: India
facility: Rajiv Gandhi Cancer Institute & Research Centre
city: Lucknow
country: India
facility: King Georges Medical University
city: Madhurai
country: India
facility: Meenakshi Mission Hospital and Research Center
city: Nadiad
country: India
facility: Muljibhai Patel Urological Hospital
city: Pune
country: India
facility: CIMET s Inamdar Multispeciality Hospital
city: Acquaviva delle Fonti
country: Italy
facility: Ente Ecclesiastico Ospedale Generale Regionale F. Miulli
city: Aosta
country: Italy
facility: Ospedale Regionale Umberto Parini
city: Cefalu
country: Italy
facility: Fondazione Istituto G. Giglio
city: Guastalla
country: Italy
facility: Ospedale Civile di Guastalla
city: Lecce
country: Italy
facility: Azienda Ospedaliera ''Vito Fazzi''
city: Macerata
country: Italy
facility: UOC Oncologia Ospedale Provinciale di Macerata
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Napoli
country: Italy
facility: Fondazione G Pascale Istituto Nazionale Tumori IRCCS
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant Andrea
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
city: Bunkyo Ku
country: Japan
facility: Juntendo University Hospital
city: Bunkyo Ku
country: Japan
facility: Tokyo Medical and Dental University Hospital
city: Chiba
country: Japan
facility: Asahi General Hospital
city: Hakodate
country: Japan
facility: Hakodate Goryoukaku Hospital
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
city: Hitachi
country: Japan
facility: Hitachi General Hospital
city: Kanagawa
country: Japan
facility: St Marianna University Hospital
city: Nagoya
country: Japan
facility: Nagoya University Hospital
city: Osaka
country: Japan
facility: JOHAS Osaka Rosai Hospital
city: Ota
country: Japan
facility: Gunma Prefectural Cancer Center
city: Takatsuki
country: Japan
facility: Osaka Medical and Pharmaceutical University Hospital
city: Tokyo
country: Japan
facility: Toranomon Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Toyoake
country: Japan
facility: Fujita Health University Hospital
city: Tsukuba City
country: Japan
facility: University of Tsukuba Hospital
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Goyang si
country: Korea, Republic of
facility: National Cancer Center
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
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: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Krakow
country: Poland
facility: Pratia MCM Krakow
city: Rzeszow
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Fryderyka Chopina w Rzeszowie
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 2 PUM
city: Warszawa
country: Poland
facility: Medical Concierge Centrum Medyczne
city: Warszawa
country: Poland
facility: City Clinic Sp. z o.o.
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny
city: Barcelona
country: Spain
facility: Fund. Puigvert
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Sabadell
country: Spain
facility: Corporacio Sanitari Parc Tauli
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan County
country: Taiwan
facility: Chang Gung Memorial Hospital- Linkou
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust Christie Hospital
city: Sheffield
country: United Kingdom
facility: Universirty of Sheffield Teaching Hospitals NHS Trust
city: Stevenage
country: United Kingdom
facility: Lister Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Han MA, Maisch P, Jung JH, Hwang JE, Narayan V, Cleves A, Hwang EC, Dahm P. Intravesical gemcitabine for non-muscle invasive bladder cancer. Cochrane Database Syst Rev. 2021 Jun 14;6(6):CD009294. doi: 10.1002/14651858.CD009294.pub3.