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)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Urinary Bladder Neoplasms
• Intervention / Treatment: Drug: Erdafitinib; Drug: Investigator Choice (Gemcitabine); Drug: Investigator Choice (Mitomycin C)

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.

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1419AHN
    • Sociedade Beneficente de Senhoras - Hospital Sírio Libanês
  • Buenos Aires, Argentina
    • Hospital Britanico de Buenos Aires
  • Ciudad Autonoma de, Argentina, C1199ABB
    • Hospital Italiano de Buenos Aires
  • Ciudad Autonoma de Buenos Aires, Argentina, C1431FWN
    • CEMIC Saavedra
  • Cordoba, Argentina, 5000
    • Cemaic - Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica
  • Cordoba, Argentina, XX5016KEH
    • Hospital Privado de Cordoba
  • Cordoba, Argentina, X5000KPH
    • Centro Urologico Profesor Bengio
• Australia
  • Bedford Park, Australia, 5042
    • Flinders Medical Centre
  • Darlinghurst, Australia, 2010
    • St. Vincent's Hospital Sydney
  • Macquarie University, Australia, 2109
    • Macquarie University
  • Melbourne, Australia, 3000
    • Peter MacCallum Cancer Centre
• Belgium
  • Gent, Belgium, 9000
    • AZ Maria Middelares
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liege, Belgium, 4000
    • CHU Sart-Tilman
  • Roeselare, Belgium, 8800
    • Algemeen Ziekenhuis Delta
• Brazil
  • Curitiba, Brazil, 81520-060
    • Liga Paranaense de Combate ao Cancer
  • Fortaleza, Brazil, 60135-237
    • Oncocentro Ceará
  • Goiania, Brazil, 74605-070
    • Associacao de Combate ao Cancer em Goias - Hospital de Cancer Araujo Jorge
  • Natal, Brazil, 59075-740
    • Liga Norte Riograndense Contra O Cancer
  • Porto Alegre, Brazil, 90050-170
    • Irmandade Santa Casa de Misericordia de Porto Alegre
  • Porto Alegre, Brazil, 91350-200
    • Hospital Nossa Senhora da Conceicao S A
  • Recife, Brazil, 50070-550
    • Instituto de Medicina Integral Professor Fernando Figueira
  • Ribeirão Preto, Brazil, 14048-900
    • Hospital Das Clinicas Da Faculdade De Medicina De RPUSP HCRP
  • Rio de Janeiro, Brazil, 22775-001
    • Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
  • Rio de Janeiro, Brazil, 22280-003
    • Comite de Etica em Pesquisa em Seres Humanos do Hospital Pro-Cardiaco CEP HPC
  • Santo Andre, Brazil, 09060-650
    • CEPHO - Centro de Estudos e Pesquisa de Hematologia e Oncologia
  • Sao Paulo, Brazil, 01246-000
    • Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo
  • Sao Paulo, Brazil, 04039-004
    • Instituto de Assistencia Medica ao Servidor Publico Estadual IAMSPE
  • São Paulo, Brazil, 01308-901
    • Sociedade Beneficente de Senhoras - Hospital Sírio Libanês
• China
  • Nanjing, China, 210008
    • Nanjing Drum Tower Hospital
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Shanghai, China, 200240
    • Renji Hospital, Shanghai Jiaotong University School of Medicine
  • Wuhan, China, 430030
    • Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
• Czechia
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u sv. Anny v Brne
  • Liberec, Czechia, 460 63
    • Krajská nemocnice Liberec
  • Praha 2, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze
  • Praha 5, Czechia, 150 06
    • Fakultni nemocnice v Motole
• France
  • Bordeaux, France, 33076
    • Hopital Pellegrin CHU Bordeaux
  • Clermont Ferrand, France, 63000
    • CHU Gabriel-Montpied
  • Lille, France, 59037
    • Hopital Huriez
  • Lyon Cedex 03, France, 69437
    • Hôpital Edouard Herriot
  • Marseille Cedex 9, France, 13273
    • Institut Paoli Calmettes
  • Paris, France, 75013
    • Hôpital Universitaire Pitié-Salpêtrière
  • Paris, France, 75877
    • Hopital Bichat Claude Bernard
  • Paris, France, 75020
    • Groupe Hospitalier Diaconesses Croix Saint Simon
  • Poitiers, France, 86021
    • CHU de Poitiers
  • Rennes Cedex, France, 35033
    • Chu Rennes Hopital Pontchaillou
  • Rouen, France, 76031
    • Hopital Charles Nicolle
  • Saint Gregoire, France, 35760
    • CHP Saint Gregoire
  • Toulouse, France, 31000
    • Institut Universitaire du Cancer Toulouse Oncopole
  • Vandœuvre-lès-Nancy Cedex, France, 54519
    • Centre Hospitalier Universitaire de Nancy - Hôpital Central
  • Villejuif Cedex, France, 94800
    • Gustave Roussy
• Germany
  • Duisburg, Germany, 47169
    • Urologicum Duisburg
  • Herne, Germany, 44625
    • Klinikum Herne - Urologie
  • Lubeck, Germany, 23538
    • Universitatsklinikum Schleswig Holstein Campus Lubeck
  • Muenchen, Germany, 81675
    • Klinikum rechts der Isar - III. Med. Klinik und Poliklinik
  • Muenster, Germany, 48149
    • Universitaetsklinikum Muenster
  • Mülheim an der Ruhr, Germany, 45468
    • Praxisklinik Urologie Rhein/Ruhr - Germany
  • Nuernberg, Germany, 90491
    • MVZ Urologie 24 gGmbH
  • Nuertingen, Germany, 72622
    • Studienpraxis Urologie Drs. Feyerabend
  • Wesseling, Germany, 50389
    • CUROS - Uberörtliche urologische Gemeinschaftspraxis
• India
  • Bangalore, India, 560027
    • Health Care Global Enterprises pvt Ltd
  • Delhi, India, 110085
    • Rajiv Gandhi Cancer Institute & Research Centre
  • Lucknow, India, 226003
    • King Georges Medical University
  • Madhurai, India, 625107
    • Meenakshi Mission Hospital and Research Center
  • Nadiad, India, 387001
    • Muljibhai Patel Urological Hospital
  • Pune, India, 411040
    • CIMET s Inamdar Multispeciality Hospital
• Italy
  • Acquaviva delle Fonti, Italy, 70021
    • Ente Ecclesiastico Ospedale Generale Regionale F. Miulli
  • Aosta, Italy, 11100
    • Ospedale Regionale Umberto Parini
  • Cefalu, Italy, 90015
    • Fondazione Istituto G. Giglio
  • Guastalla, Italy, 42016
    • Ospedale Civile di Guastalla
  • Lecce, Italy, 73100
    • Azienda Ospedaliera ''Vito Fazzi''
  • Macerata, Italy, 62100
    • UOC Oncologia Ospedale Provinciale di Macerata
  • Milan, Italy, 20132
    • IRCCS Ospedale San Raffaele
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Napoli, Italy, 80138
    • Fondazione G. Pascale - Istituto Nazionale Tumori IRCCS
  • Roma, Italy, 00189
    • Azienda Ospedaliera Sant Andrea
  • Verona, Italy, 37126
    • Azienda Ospedaliera Universitaria Integrata Verona
• Japan
  • Bunkyo-Ku, Japan, 113-8519
    • Tokyo Medical and Dental University Hospital
  • Bunkyo-Ku, Japan, 113-8431
    • Juntendo University Hospital
  • Chiba, Japan, 289-2511
    • Asahi General Hospital
  • Hakodate, Japan, 040-8611
    • Hakodate Goryokaku Hospital
  • Hidaka, Japan, 350-1298
    • Saitama Medical University International Medical Center
  • Hitachi, Japan, 317-0077
    • Hitachi General Hospital
  • Kanagawa, Japan, 216-8511
    • St Marianna University Hospital
  • Nagoya, Japan, 466-8560
    • Nagoya University Hospital
  • Osaka, Japan, 591-8025
    • JOHAS Osaka Rosai Hospital
  • Ota, Japan, 373 8550
    • Gunma Prefectural Cancer Center
  • Takatsuki, Japan, 569-8686
    • Osaka Medical and Pharmaceutical University Hospital
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital
  • Tokyo, Japan, 135 8550
    • The Cancer Institute Hospital of JFCR
  • Toyoake, Japan, 470-1192
    • Fujita Health University Hospital
  • Tsukuba-City, Japan, 305-8576
    • University of Tsukuba Hospital
  • Yokohama, Japan, 232 0024
    • Yokohama City University Medical Center
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Cheongju, Korea, Republic of, 361-711
    • Chungbuk National University Hospital
  • Daegu, Korea, Republic of, 41404
    • Kyungpook National University Chilgok Hospital
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Jeollanam-do, Korea, Republic of, 58128
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03181
    • Kangbuk Samsung Hospital
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Krakow, Poland, 30-727
    • Pratia MCM Krakow
  • Rzeszow, Poland, 35-055
    • Uniwersytecki Szpital Kliniczny Im. Fryderyka Chopina W Rzeszowie
  • Szczecin, Poland, 70-111
    • Samodzielny Publiczny Szpital Kliniczny nr 2 PUM
  • Warszawa, Poland, 02-798
    • Medical Concierge Centrum Medyczne
  • Warszawa, Poland, 02-473
    • City Clinic Sp. z o.o.
  • Wroclaw, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny
• Spain
  • Barcelona, Spain, 08025
    • Fund. Puigvert
  • Barcelona, Spain, 8036
    • Hosp. Clinic de Barcelona
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28034
    • Hosp. Univ. Ramon Y Cajal
  • Madrid, Spain, 28046
    • Hosp. Univ. La Paz
  • Sabadell, Spain, 08208
    • Corporacio Sanitari Parc Tauli
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncologia
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan County, Taiwan, 33305
    • Chang Gung Memorial Hospital- Linkou
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust Christie Hospital
  • Sheffield, United Kingdom, S10 2JF
    • Universirty of Sheffield Teaching Hospitals NHS Trust
  • Stevenage, United Kingdom, SG1 4AB
    • Lister Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85741
      • Urological Associates of Southern Arizona, P.C.
  • California
    • Los Angeles, California, United States, 90033
      • USC Institute of Urology
  • Colorado
    • Denver, Colorado, United States, 80211
      • The Urology Center of Colorado
  • Florida
    • Hialeah, Florida, United States, 33016
      • Urological Research Network
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University - Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Springfield, Illinois, United States, 62702
      • Simmons Cancer Institute
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • New York, New York, United States, 10016
      • NYU Langone Health
    • Sanborn, New York, United States, 14132
      • Great Lakes Physician PC d/b/a Western New York Urology Associates
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • The Urology Group
    • Columbus, Ohio, United States, 43221
      • The Ohio State University- James Cancer Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • MidLantic Urology
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center - Cancer Centers
  • Tennessee
    • Nashville, Tennessee, United States, 37209
      • Urology Associates
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
  • Washington
    • Seattle, Washington, United States, 98008
      • University of Washington
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Erdafitinib; Participants with high-risk non-muscle-invasive bladder cancer (NMIBC) presenting as papillary tumor only (carcinoma in situ [CIS], absent), with disease recurrence after bacillus Calmette- Guerin (BCG) therapy will receive treatment with erdafitinib.	Drug: Erdafitinib; Participants will receive erdafitinib orally beginning on Cycle 1 Day 1 until 2 years of treatment have been completed, disease recurrence, intolerable toxicity, withdrawal of consent, a decision by the investigator to discontinue treatment, or study termination, whichever occurs first. Each cycle is of 28 days.; Other Names: JNJ-42756493
Experimental: Cohort 2; Participants with high-risk, BCG- unresponsive NMIBC presenting as CIS with or without concurrent papillary tumor will receive treatment with erdafitinib.	Drug: Erdafitinib; Participants will receive erdafitinib orally beginning on Cycle 1 Day 1 until 2 years of treatment have been completed, disease recurrence, intolerable toxicity, withdrawal of consent, a decision by the investigator to discontinue treatment, or study termination, whichever occurs first. Each cycle is of 28 days.; Other Names: JNJ-42756493
Experimental: Cohort 3; Marker lesion study in intermediate-risk NMIBC presenting as papillary disease only. All enrolled participants will receive treatment with erdafitinib.	Drug: Erdafitinib; Participants will receive erdafitinib orally beginning on Cycle 1 Day 1 until 2 years of treatment have been completed, disease recurrence, intolerable toxicity, withdrawal of consent, a decision by the investigator to discontinue treatment, or study termination, whichever occurs first. Each cycle is of 28 days.; Other Names: JNJ-42756493
Active Comparator: Cohort 1: Investigators Choice; Participants with high-risk NMIBC presenting as papillary tumor only (CIS, absent), with disease recurrence after BCG therapy will receive the investigator's choice of either intravesical gemcitabine or intravesical mitomycin C (MMC) or hyperthermic MMC. Participants who are randomized to gemcitabine or MMC or hyperthermic MMC in Cohort 1 and demonstrate a recurrence via investigator disease assessment will have the opportunity to cross over to treatment with erdafitinib.	Drug: Investigator Choice (Gemcitabine); Investigator's Choice treatment will be given once weekly for at least 4 doses of induction followed by monthly maintenance for at least 6 months.; Drug: Investigator Choice (Mitomycin C); Investigator's Choice treatment will be given once weekly for at least 4 doses of induction followed by monthly maintenance for at least 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-Free Survival (RFS)	RFS is defined as the time from the date of randomization until the date of the reappearance of high-risk disease, or death, whichever is reported first.	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression	Time from the date of randomization until the date of first documented evidence of any of progression or death. Participants who are progression -free and alive or have unknown status will be censored at the date of the last tumor assessment.	Up to 4 years
Overall Survival	The time from the date of randomization to the date of the participant's death resulting from any cause. Participants who are alive or have unknown vital status will be censored at the date the participant was last known to be alive.	Up to 4 years
Plasma Concentration of Erdafitinib	Plasma concentration of erdafitinib will be reported.	Cycle 1 Day 14, Cycle 2 Day 1 (each cycle is of 28 days)
Number of Participants with Adverse events	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product	Up to 4 years
Recurrence-Free Survival	RFS is defined as the time from the date of randomization until the date of the reappearance of high-risk disease, or death, whichever is reported first. Participants who are recurrence-free and alive or have unknown status will be censored at the last tumor assessment.	Months 6 and 12

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2020
• Primary Completion (Estimated): March 29, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: November 20, 2019
• First Submitted That Met QC Criteria: November 20, 2019
• First Posted (Actual): November 21, 2019

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Non muscle invasive bladder cancer (NMIBC); Bacillus calmette- guerin (BCG) failure; BCG unresponsive
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Mitomycins; Mitomycin; Gemcitabine
• Other Study ID Numbers: CR108699; 2019-002449-39 (EudraCT Number); 42756493BLC2003 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No