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)

NCT ID: NCT04172675

Last Updated: 2025-08-01

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

107 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-28

Study Completion Date

2025-02-27

Brief Summary

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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

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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.

Conditions

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Urinary Bladder Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Erdafitinib

Intervention Type DRUG

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.

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.

Group Type ACTIVE_COMPARATOR

Investigator Choice (Gemcitabine)

Intervention Type DRUG

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)

Intervention Type DRUG

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.

Cohort 2

Participants with high-risk, BCG- unresponsive NMIBC presenting as CIS with or without concurrent papillary tumor will receive treatment with erdafitinib.

Group Type EXPERIMENTAL

Erdafitinib

Intervention Type DRUG

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.

Cohort 3

Marker lesion study in intermediate-risk NMIBC presenting as papillary disease only. All enrolled participants will receive treatment with erdafitinib.

Group Type EXPERIMENTAL

Erdafitinib

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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JNJ-42756493

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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Urological Associates of Southern Arizona, P.C.

Tucson, Arizona, United States

Site Status

USC Institute of Urology

Los Angeles, California, United States

Site Status

The Urology Center of Colorado

Denver, Colorado, United States

Site Status

Urological Research Network

Hialeah, Florida, United States

Site Status

Emory University Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Simmons Cancer Institute

Springfield, Illinois, United States

Site Status

University of Kansas

Westwood, Kansas, United States

Site Status

Albany Medical College

Albany, New York, United States

Site Status

NYU Langone Health

New York, New York, United States

Site Status

Great Lakes Physician PC d/b/a Western New York Urology Associates

Sanborn, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

The Urology Group

Cincinnati, Ohio, United States

Site Status

The Ohio State University- James Cancer Hospital

Columbus, Ohio, United States

Site Status

Oregon Health And Science University

Portland, Oregon, United States

Site Status

MidLantic Urology

Bala-Cynwyd, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center - Cancer Centers

Pittsburgh, Pennsylvania, United States

Site Status

Urology Associates

Nashville, Tennessee, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Medical College of Wisconsin Froedtert Hospital

Milwaukee, Wisconsin, United States

Site Status

Sociedade Beneficente de Senhoras Hospital Sirio Libanes

Buenos Aires, , Argentina

Site Status

CEMIC Saavedra

Buenos Aires, , Argentina

Site Status

Hospital Britanico de Buenos Aires

Buenos Aires, , Argentina

Site Status

Hospital Italiano de Buenos Aires

Ciudad Autonoma de, , Argentina

Site Status

Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica

Córdoba, , Argentina

Site Status

Centro Urologico Profesor Bengio

Córdoba, , Argentina

Site Status

Hospital Privado de Cordoba

Córdoba, , Argentina

Site Status

Flinders Medical Centre

Bedford Park, , Australia

Site Status

St Vincent s Hospital Sydney

Darlinghurst, , Australia

Site Status

Macquarie University

Macquarie University, , Australia

Site Status

Peter MacCallum Cancer Centre

Melbourne, , Australia

Site Status

AZ Maria Middelares

Ghent, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

CHU Sart-Tilman

Liège, , Belgium

Site Status

Algemeen Ziekenhuis Delta

Roeselare, , Belgium

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Liga Paranaense de Combate ao Cancer

Curitiba, , Brazil

Site Status

Oncocentro Ceará

Fortaleza, , Brazil

Site Status

Associacao de Combate ao Cancer em Goias - Hospital de Cancer Araujo Jorge

Goiânia, , Brazil

Site Status

Liga Norte Riograndense Contra O Cancer

Natal, , Brazil

Site Status

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, , Brazil

Site Status

Hospital Nossa Senhora da Conceicao S A

Porto Alegre, , Brazil

Site Status

Instituto de Medicina Integral Professor Fernando Figueira

Recife, , Brazil

Site Status

Hospital Das Clinicas Da Faculdade De Medicina De RPUSP HCRP

Ribeirão Preto, , Brazil

Site Status

Oncoclinicas Rio de Janeiro S A

Rio de Janeiro, , Brazil

Site Status

Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)

Rio de Janeiro, , Brazil

Site Status

CEPHO Centro de Estudos e Pesquisa de Hematologia e Oncologia

Santo André, , Brazil

Site Status

Fundacao Faculdade de Medicina Instituto do Cancer do Estado de Sao Paulo

São Paulo, , Brazil

Site Status

Sociedade Beneficente de Senhoras Hospital Sirio Libanes

São Paulo, , Brazil

Site Status

Instituto de Assistencia Medica ao Servidor Publico Estadual IAMSPE

São Paulo, , Brazil

Site Status

Nanjing Drum Tower Hospital

Nanjing, , China

Site Status

Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status

Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, , China

Site Status

Tongji Hospital Tongji Medical College of Huazhong University of Science and Technology

Wuhan, , China

Site Status

Fakultni nemocnice u sv. Anny v Brne

Brno, , Czechia

Site Status

Krajská nemocnice Liberec

Liberec, , Czechia

Site Status

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

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Fakultni nemocnice v Motole

Prague, , Czechia

Site Status

Hopital Pellegrin CHU Bordeaux

Bordeaux, , France

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CHU Gabriel-Montpied

Clermont-Ferrand, , France

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Hopital Huriez

Lille, , France

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Hôpital Edouard Herriot

Lyon, , France

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Institut Paoli Calmettes

Marseille, , France

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Hôpital Universitaire Pitié-Salpêtrière

Paris, , France

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Groupe Hospitalier Diaconesses Croix Saint Simon

Paris, , France

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Hopital Bichat Claude Bernard

Paris, , France

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CHU De Poitiers

Poitiers, , France

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Chu Rennes Hopital Pontchaillou

Rennes, , France

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Hopital Charles Nicolle

Rouen, , France

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CHP Saint Gregoire

Saint-Grégoire, , France

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Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, , France

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Centre Hospitalier Universitaire de Nancy - Hôpital Central

Vandœuvre-lès-Nancy, , France

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Gustave Roussy

Villejuif, , France

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Urologicum Duisburg

Duisburg, , Germany

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Klinikum Herne - Urologie

Herne, , Germany

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Universitatsklinikum Schleswig Holstein Campus Lubeck

Lübeck, , Germany

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Praxisklinik Urologie Rhein/Ruhr - Germany

Mülheim, , Germany

Site Status

Klinikum rechts der Isar - III. Med. Klinik und Poliklinik

München, , Germany

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Universitaetsklinikum Muenster

Münster, , Germany

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MVZ Urologie 24 gGmbH

Nuremberg, , Germany

Site Status

Studienpraxis Urologie Drs. Feyerabend

Nürtingen, , Germany

Site Status

CUROS - Uberörtliche urologische Gemeinschaftspraxis

Wesseling, , Germany

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Health Care Global Enterprises pvt Ltd

Bangalore, , India

Site Status

Rajiv Gandhi Cancer Institute & Research Centre

Delhi, , India

Site Status

King Georges Medical University

Lucknow, , India

Site Status

Meenakshi Mission Hospital and Research Center

Madurai, , India

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Muljibhai Patel Urological Hospital

Nadiād, , India

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CIMET s Inamdar Multispeciality Hospital

Pune, , India

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Ente Ecclesiastico Ospedale Generale Regionale F. Miulli

Acquaviva delle Fonti, , Italy

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Ospedale Regionale Umberto Parini

Aosta, , Italy

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Fondazione Istituto G. Giglio

Cefalù, , Italy

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Ospedale Civile di Guastalla

Guastalla, , Italy

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Azienda Ospedaliera ''Vito Fazzi''

Lecce, , Italy

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UOC Oncologia Ospedale Provinciale di Macerata

Macerata, , Italy

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IRCCS Ospedale San Raffaele

Milan, , Italy

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Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

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Fondazione G Pascale Istituto Nazionale Tumori IRCCS

Napoli, , Italy

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Azienda Ospedaliera Sant Andrea

Roma, , Italy

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Azienda Ospedaliera Universitaria Integrata Verona

Verona, , Italy

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Juntendo University Hospital

Bunkyō City, , Japan

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Tokyo Medical and Dental University Hospital

Bunkyō City, , Japan

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Asahi General Hospital

Chiba, , Japan

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Hakodate Goryoukaku Hospital

Hakodate, , Japan

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Saitama Medical University International Medical Center

Hidaka, , Japan

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Hitachi General Hospital

Hitachi, , Japan

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St Marianna University Hospital

Kanagawa, , Japan

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Nagoya University Hospital

Nagoya, , Japan

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JOHAS Osaka Rosai Hospital

Osaka, , Japan

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Gunma Prefectural Cancer Center

Ōta-ku, , Japan

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Osaka Medical and Pharmaceutical University Hospital

Takatsuki, , Japan

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Toranomon Hospital

Tokyo, , Japan

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The Cancer Institute Hospital of JFCR

Tokyo, , Japan

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Fujita Health University Hospital

Toyoake, , Japan

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University of Tsukuba Hospital

Tsukuba, , Japan

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Yokohama City University Medical Center

Yokohama, , Japan

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Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

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Pratia MCM Krakow

Krakow, , Poland

Site Status

Uniwersytecki Szpital Kliniczny im. Fryderyka Chopina w Rzeszowie

Rzeszów, , Poland

Site Status

Samodzielny Publiczny Szpital Kliniczny nr 2 PUM

Szczecin, , Poland

Site Status

Medical Concierge Centrum Medyczne

Warsaw, , Poland

Site Status

City Clinic Sp. z o.o.

Warsaw, , Poland

Site Status

Uniwersytecki Szpital Kliniczny

Wroclaw, , Poland

Site Status

Pusan National University Hospital

Busan, , South Korea

Site Status

Chungbuk National University Hospital

Cheongju-si, , South Korea

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Kyungpook National University Chilgok Hospital

Daegu, , South Korea

Site Status

National Cancer Center

Goyang-si, , South Korea

Site Status

Chonnam National University Hwasun Hospital

Jeollanam-do, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

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Seoul National University Hospital

Seoul, , South Korea

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Kangbuk Samsung Hospital

Seoul, , South Korea

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Severance Hospital Yonsei University Health System

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Fund. Puigvert

Barcelona, , Spain

Site Status

Hosp Clinic de Barcelona

Barcelona, , Spain

Site Status

Hosp. Univ. Ramon Y Cajal

Madrid, , Spain

Site Status

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Site Status

Hosp. Univ. La Paz

Madrid, , Spain

Site Status

Corporacio Sanitari Parc Tauli

Sabadell, , Spain

Site Status

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

Site Status

Instituto Valenciano de Oncologia

Valencia, , Spain

Site Status

Kaohsiung Medical University Chung Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Chang Gung Memorial Hospital- Linkou

Taoyuan, , Taiwan

Site Status

The Christie NHS Foundation Trust Christie Hospital

Manchester, , United Kingdom

Site Status

Universirty of Sheffield Teaching Hospitals NHS Trust

Sheffield, , United Kingdom

Site Status

Lister Hospital

Stevenage, , United Kingdom

Site Status

Countries

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

References

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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.

Reference Type DERIVED
PMID: 34125951 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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42756493BLC2003

Identifier Type: OTHER

Identifier Source: secondary_id

2019-002449-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-510306-40-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR108699

Identifier Type: -

Identifier Source: org_study_id

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