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)

Urinary Bladder Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04172675
• Other study ID #: CR108699
• Secondary ID: 2019-002449-3942
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 28, 2020
• Est. completion date: March 1, 2025

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 107
• Est. completion date: March 1, 2025
• Est. primary completion date: July 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Urinary Bladder Neoplasms

Intervention

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.
• 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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  China,  Czechia,  France,  Germany,  India,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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