Trial Condition(s):

Carcinoma, Transitional Cell

Study of rogaratinib (BAY1163877) vs chemotherapy in patients with FGFR (Fibroblast growth factor receptor)-positive locally advanced or metastatic urothelial carcinoma (FORT-1)

Bayer Identifier:

17403

ClinicalTrials.gov Identifier:

NCT03410693

EudraCT Number:

2016-004340-11

Study Completed

Trial Purpose

This is a randomized, open-label, multicenter Phase 2/3 study to evaluate the efficacy and safety of rogaratinib (BAY 1163877) compared to chemotherapy in patients with FGFR-positive locally advanced or metastatic urothelial carcinoma who have received prior platinum-containing chemotherapy.
The primary objective is to demonstrate the superiority of rogaratinib over chemotherapy in terms of objective response rate (before: overall survivial) of urothelial carcinoma patients with FGFR positive tumors.
At randomization, patients will have locally advanced or metastatic urothelial carcinoma and have received at least one prior platinum-containing chemotherapy regimen. Only patients with FGFR1 or 3 positive tumors can be randomized into the study. Archival tumor tissue is adequate for testing of FGFR1 and 3 mRNA expressions, which will be determined centrally using an RNA in situ hybridization (RNA-ISH) test. Approximately 42 % of UC patients with locally advanced or metastatic UC are identified as FGFR-positive by the RNA-ISH cut-off applied.

Inclusion Criteria
- Existence of archival or fresh biopsy for FGFR testing. Mandatory FGFR testing of patients will be performed prior to start of screening. The timing of the FGFR test is at the discretion of the investigator. Investigators should ensure all patients will be eligible in terms of disease status and lines of treatment.
 - Documented urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra meeting all of the following criteria
 -- Histologically confirmed (Patients with mixed histologies are required to have a dominant transitional cell pattern.)
 -- Locally advanced (T4, any N; or any T, N 2−3) or metastatic disease (any T, any N and M1). Locally advanced bladder cancer must be unresectable i.e. invading the pelvic or abdominal wall (stage T4b) or presenting with bulky nodal disease (N2-3).
 - ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 or 1
 - Disease progression during or following treatment with at least one platinum-containing regimen (patients should have been treated for at least 2 cycles). In patients who received prior adjuvant/ neoadjuvant platinum-containing chemotherapy, progression had to occur within 12 months of treatment.
 - High FGFR1 or 3 mRNA expression levels in archival or fresh tumor biopsy specimen quantified as outlined in the lab manual
 - At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) in contrast enhanced (unless contraindicated) CT or MRI
Exclusion Criteria
- Previous or concurrent cancer except
 -- cervical carcinoma in situ
 -- treated basal-cell or squamous cell skin carcinoma
 -- any cancer curatively treated > 3 years before randomization
 -- curatively treated incidental prostate cancer (T1/T2a)
 - Ongoing or previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors including rogaratinib or FGFR-specific antibodies) or with taxanes or vinflunine
 - More than two prior lines of systemic anti-cancer therapy for urothelial carcinoma given for advanced unresectable/ metastatic disease
 - Ongoing or previous anti-cancer treatment within 4 weeks before randomization.
 - Unresolved toxicity higher than National Cancer Institute’s Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE v.4.03) Grade 1 attributed to any prior therapy/ procedure excluding alopecia, anemia and/ or hypothyroidism
 - History or current condition of an uncontrolled cardiovascular disease including any of the following conditions:
 -- Congestive heart failure (CHF) NYHA (New York Heart Association) > Class 2
 -- Unstable angina (symptoms of angina at rest) or new-onset angina (within last 3 months before randomization)
 -- Myocardial infarction (MI) within past 6 months before randomization
 -- Unstable cardiac arrhythmias requiring anti-arrhythmic therapy. Patients with arrhythmia under control with anti-arrhythmic therapy such as beta-blockers or digoxin are eligible.
 - Arterial or venous thrombotic events or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before randomization
 - Current evidence of endocrine alteration of calcium phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis, paraneoplastic hypercalcemia)
 - Current diagnosis of any retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion
 - Any hemorrhage / bleeding event ≥ CTCAE v.4.03 Grade 3 within 4 weeks before randomization

Trial Summary

Enrollment Goal
175
Trial Dates
black-arrow
Phase
2/3
Could I receive a placebo?
No
Products
Rogaratinib (BAY1163877)
Accepts Healthy Volunteers
No

Where to Participate

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Locations
Status
LocationsStatus
Locations

Hospital del Mar

Barcelona, Spain, 08003

Status
Completed
 
Locations

Ciutat Sanitària i Universitaria de la Vall d'Hebron

Barcelona, Spain, 08035

Status
Completed
 
Locations

Hospital Ramón y Cajal

Madrid, Spain, 28034

Status
Completed
 
Locations

Hospital Universitari Son Espases

Palma de Mallorca, Spain, 07120

Status
Completed
 
Locations

Hospital Virgen de la Victoria

Málaga, Spain, 29010

Status
Completed
 
Locations

Instituto Valenciano de Oncología

Valencia, Spain, 46009

Status
Completed
 
Locations

Hospital Reina Sofía

Córdoba, Spain, 14004

Status
Completed
 
Locations

Institut Català d'Oncologia Badalona

Badalona, Spain, 08916

Status
Completed
 
Locations

Hospital San Pedro de Alcántara

Cáceres, Spain, 10003

Status
Completed
 
Locations

Hospital General Universitario de Valencia

Valencia, Spain, 46014

Status
Completed
 
Locations

Narodny onkologicky ustav

Bratislava, Slovakia, 833 10

Status
Completed
 
Locations

POKO Poprad s.r.o.

Poprad, Slovakia, 085 01

Status
Completed
 
Locations

UROEXAM, spol. s r.o.

Nitra, Slovakia, 949 01

Status
Completed
 
Locations

Asan Medical Center

Seoul, South Korea, 05505

Status
Completed
 
Locations

Severance Hospital, Yonsei University Health System

Seoul, South Korea, 03722

Status
Completed
 
Locations

Samsung Medical Center

Seoul, South Korea, 06351

Status
Completed
 
Locations

National Cancer Center

Goyang-si, South Korea, 10408

Status
Completed
 
Locations

Fondazione IRCCS Istituto Nazionale dei Tumori

Milano, Italy, 20133

Status
Completed
 
Locations

A.O. San Camillo-Forlanini

Roma, Italy, 00152

Status
Completed
 
Locations

IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)

Milano, Italy, 20141

Status
Completed
 
Locations

A.O.U. Pisana

Pisa, Italy, 56126

Status
Completed
 
Locations

IRST Istituto Scientifico Romagnolo per studio e cura tumori

Forlì Cesena, Italy, 47014

Status
Completed
 
Locations

A.O.U. San Luigi Gonzaga

Torino, Italy, 10043

Status
Completed
 
Locations

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, Italy, 00168

Status
Completed
 
Locations

A.O.U.I. Verona

Verona, Italy, 37134

Status
Completed
 
Locations

A.O.U. di Modena - Policlinico

Modena, Italy, 41124

Status
Completed
 
Locations

AUSL Modena

Modena, Italy, 41012

Status
Completed
 
Locations

Kantonsspital Graubünden

Chur, Switzerland, 7000

Status
Completed
 
Locations

Universitätsspital Basel

Basel, Switzerland, 4031

Status
Completed
 
Locations

Prince of Wales Hospital Hong Kong

Shatin, Hong Kong, China

Status
Completed
 
Locations

Universitätsklinikum AKH Wien

Wien, Austria, 1090

Status
Completed
 
Locations

Krankenhaus der Barmherzigen Brüder

Wien, Austria, 1020

Status
Completed
 
Locations

Klinik Ottakring - Wilhelminenspital

Wien, Austria, 1160

Status
Completed
 
Locations

Landesklinikum Krems

Krems, Austria, 3500

Status
Completed
 
Locations

Taipei Veterans General Hospital

Taipei, Taiwan, China, 11217

Status
Completed
 
Locations

Chang Gung Memorial Hospital at Linkou

Taoyuan, Taiwan, China, 33305

Status
Completed
 
Locations

National Cheng Kung University Hospital

Tainan, Taiwan, China, 704

Status
Completed
 
Locations

Taichung Veterans General Hospital

Taichung, Taiwan, China, 40705

Status
Completed
 
Locations

National Taiwan University Hospital

Taipei, Taiwan, China, 10002

Status
Completed
 
Locations

National University Hospital

Singapore, Singapore, 119074

Status
Completed
 
Locations

National Cancer Center Singapore

Singapore, Singapore, 169610

Status
Completed
 
Locations

Hopital Jean Minjoz

BESANCON, France, 25030

Status
Completed
 
Locations

Cochin - Paris

PARIS, France, 75674

Status
Completed
 
Locations

Centre Oscar Lambret - Lille

LILLE CEDEX, France, 59020

Status
Completed
 
Locations

Centre Léon Bérard

LYON CEDEX, France, 69008

Status
Completed
 
Locations

Centre de Lutte Contre le Cancer François Baclesse

CAEN CEDEX 5, France, 14076

Status
Completed
 
Locations

Institut Paoli-Calmettes - Marseille

MARSEILLE, France, 13273

Status
Completed
 
Locations

Princess Margaret Hospital-University Health Network

Toronto, Canada, M5G 2M9

Status
Completed
 
Locations

Fakultni Thomayerova Nemocnice

Praha 4 - Krc, Czech Republic, 140 59

Status
Completed
 
Locations

Fakultni nemocnice Kralovske Vinohrady

Praha 10, Czech Republic, 10034

Status
Completed
 
Locations

Fakultni nemocnice Ostrava

Ostrava, Czech Republic, 708 52

Status
Completed
 
Locations

Hadassah Hebrew University Hospital Ein Kerem

Jerusalem, Israel, 9112001

Status
Completed
 
Locations

Clalit Health Services Rabin Medical Center-Beilinson Campus

Petah Tikva, Israel, 4941492

Status
Completed
 
Locations

Chaim Sheba Medical Center

Ramat Gan, Israel, 5266202

Status
Completed
 
Locations

Meir Medical Center

Kfar Saba, Israel, 4428164

Status
Completed
 
Locations

Rambam Health Corporation

Haifa, Israel, 3109601

Status
Completed
 
Locations

Moscow Scient. Res. Institute of Oncology n.a P.A. Hertzen

Moscow, Russia, 125284

Status
Completed
 
Locations

Bashkir State Medical University

Ufa, Russia, 450008

Status
Completed
 
Locations

Clinical Oncological Dispensary of Omsk Region

Omsk, Russia, 644013

Status
Completed
 
Locations

Krasnoyarsk Regional Clinical Oncology Dispensary

Krasnoyarsk, Russia, 660133

Status
Completed
 
Locations

Volga District Med Center FMBA

Nizhny Novgorod, Russia, 603109

Status
Completed
 
Locations

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Status
Completed
 
Locations

Centro Hospitalar Universitario do Porto

Porto, Portugal, 4099-001

Status
Completed
 
Locations

IPO Coimbra

Coimbra, Portugal, 3000-075

Status
Completed
 
Locations

CHULN - Hospital Santa Maria

Lisboa, Portugal, 1649-035

Status
Completed
 
Locations

Hospital Beatriz Angelo

Loures, Portugal, 2674-514

Status
Completed
 
Locations

Rigshospitalet

København, Denmark, 2100

Status
Completed
 
Locations

Herlev Hospital - Oncology Research Dept.

Herlev, Denmark, 2730

Status
Completed
 
Locations

Aarhus Universitetshospital, Skejby

Aarhus N, Denmark, 8200

Status
Completed
 
Locations

Institut Català d'Oncologia Hospitalet

L'Hospitalet de Llobregat, Spain, 08907

Status
Completed
 
Locations

Kantonsspital St. Gallen

St. Gallen, Switzerland, 9007

Status
Completed
 
Locations

Docrates Klinikka

Helsinki, Finland, 00180

Status
Completed
 
Locations

Hôpital Saint André - Bordeaux

BORDEAUX, France, 33000

Status
Completed
 
Locations

Clinique Saint Anne

STRASBOURG, France, 67000

Status
Completed
 
Locations

Hôpital d'Instruction des Armées Begin

SAINT MANDE, France, 94160

Status
Completed
 
Locations

Centre Médico-Chirurgical Foch

SURESNES, France, 92151

Status
Completed
 
Locations

AMNCH

Dublin, Ireland, 24

Status
Completed
 
Locations

Cork University Hospital

Cork, Ireland

Status
Completed
 
Locations

Alaska Clinical Research Center, LLC

Anchorage, United States, 99503

Status
Completed
 
Locations

University of Arizona Cancer Center

Tuscon, United States, 85719

Status
Completed
 
Locations

Northern Cancer Institute

St Leonards, Australia, 2065

Status
Completed
 
Locations

Macquarie University Hospital

Sydney, Australia, 2109

Status
Completed
 
Locations

Mid North Coast Cancer Institute

Coffs Harbour, Australia, 2450

Status
Completed
 
Locations

Monash Medical Centre

Clayton, Australia, 3168

Status
Completed
 
Locations

Pindara Private Hospital

Benowa, Australia, 4217

Status
Completed
 
Locations

Riverina Cancer Care Centre

Wagga Wagga, Australia, 2650

Status
Completed
 
Locations

Eberhard-Karls-Universität Tübingen

Tübingen, Germany, 72076

Status
Completed
 
Locations

Heinrich-Heine-Universität Düsseldorf

Düsseldorf, Germany, 40225

Status
Completed
 
Locations

Universitätsmedizin der Johannes Gutenberg Universität Mainz

Mainz, Germany, 55131

Status
Completed
 
Locations

Hospital CUF Infante Santo

Lisboa, Portugal, 1350-070

Status
Completed
 
Locations

Södersjukhuset

Stockholm, Sweden, 118 83

Status
Completed
 
Locations

Centrum Onkologii im. Prof. Franciszka Lukaszczyka

Bydgoszcz, Poland, 85-796

Status
Completed
 
Locations

Uniwersytecki Szpital Kliniczny UM we Wroclawiu

Wroclaw, Poland, 50-556

Status
Completed
 
Locations

Swietokrzyskie Centrum Onkologii

Kielce, Poland, 25-734

Status
Completed
 
Locations

Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc

Olsztyn, Poland, 10-357

Status
Completed
 
Locations

Przychodnia Lekarska KOMED

Konin, Poland, 62-500

Status
Completed
 
Locations

Szpital Kliniczny Przemienienia Panskiego

Poznan, Poland, 60-569

Status
Completed
 
Locations

Orszagos Onkologiai Intezet

Budapest, Hungary, 1122

Status
Completed
 
Locations

Pecsi Tudomanyegyetem Klinikai Kozpont

Pecs, Hungary, 7624

Status
Completed
 
Locations

MH Egeszsegugyi Kozpont

Budapest, Hungary, 1062

Status
Completed
 
Locations

Virginia Mason Medical Center

Seattle, United States, 98101

Status
Completed
 
Locations

UC Davis Comprehensive Cancer Center

Sacramento, United States, 95817

Status
Completed
 
Locations

UZ Gent

GENT, Belgium, 9000

Status
Completed
 
Locations

Clinique Saint-Pierre

OTTIGNIES, Belgium, 1340

Status
Completed
 
Locations

UZ Leuven Gasthuisberg

LEUVEN, Belgium, 3000

Status
Completed
 
Locations

Royal Marsden Hospital (London)

London, United Kingdom, SW3 6JJ

Status
Terminated
 
Locations

University of Kansas Medical Center

Westwood, United States, 66205

Status
Completed
 
Locations

Houston Methodist Hospital

Houston, United States, 77030-2707

Status
Completed
 
Locations

University of Southern California

Los Angeles, United States, 90033

Status
Completed
 
Locations

Sapporo Medical University Hospital

Sapporo, Japan, 060-8543

Status
Completed
 
Locations

Hirosaki University Hospital

Hirosaki, Japan, 036-8563

Status
Completed
 
Locations

Iwate Medical University Hospital

Morioka, Japan, 028-3695

Status
Completed
 
Locations

Niigata University Medical and Dental Hospital

Niigata, Japan, 951-8520

Status
Completed
 
Locations

University of Tsukuba Hospital

Tsukuba, Japan, 305-8576

Status
Completed
 
Locations

The Cancer Institute Hospital of JFCR

Koto-ku, Japan, 135-8550

Status
Completed
 
Locations

Nagoya University Hospital

Nagoya, Japan, 466-8560

Status
Completed
 
Locations

Osaka International Cancer Institute

Osaka, Japan, 541-8567

Status
Completed
 
Locations

Kindai University Hospital

Osakasayama, Japan, 589-8511

Status
Completed
 
Locations

Hiroshima City Hiroshima Citizens Hospital

Hiroshima, Japan, 730-8518

Status
Completed
 
Locations

Kyushu University Hospital

Fukuoka, Japan, 812-8582

Status
Completed
 
Locations

Hokkaido University Hospital

Sapporo, Japan, 060-8648

Status
Completed
 
Locations

Gunma Prefectural Cancer Center

Ota, Japan, 373-8550

Status
Completed
 
Locations

Saitama Medical University International Medical Center

Hidaka, Japan, 350-1298

Status
Completed
 
Locations

Keio University Hospital

Shinjuku-ku, Japan, 160-8582

Status
Completed
 
Locations

National Cancer Center Hospital

Chuo-ku, Japan, 104-0045

Status
Completed
 
Locations

Nippon Medical School Hospital

Bunkyo-ku, Japan, 113-8603

Status
Completed
 
Locations

Yokohama City University Hospital

Yokohama, Japan, 236-0004

Status
Completed
 
Locations

Toyama University Hospital

Toyama, Japan, 930-0194

Status
Completed
 
Locations

Kobe City Medical Center General Hospital

Kobe, Japan, 650-0047

Status
Completed
 
Locations

Kumamoto University Hospital

Kumamoto, Japan, 860-8556

Status
Completed
 
Locations

Ottawa Hospital-General Campus

Ottawa, Canada, K1H 8L6

Status
Completed
 
Locations

Sydney Adventist Hospital

Wahroonga, Australia, 2076

Status
Completed
 
Locations

Erasmus Medisch Centrum

ROTTERDAM, Netherlands, 3075 EA

Status
Completed
 
Locations

Nederlands Kanker Instituut

AMSTERDAM, Netherlands, 1066 CX

Status
Completed
 
Locations

ASST Grande Ospedale Metropolitano Niguarda

Milano, Italy, 20162

Status
Completed
 
Locations

Sir Mortimer B. Davis Jewish General Hospital

Montreal, Canada, H3T 1E2

Status
Completed
 
Locations

Centre Jean Perrin

CLERMONT FERRAND CEDEX 1, France, 63011

Status
Completed
 
Locations

Gunma University Hospital

Maebashi, Japan, 371-8511

Status
Completed
 
Locations

Karolinska Institutet

Stockholm, Sweden, 17167

Status
Completed
 
Locations

Akita University Hospital

Akita, Japan, 010-8543

Status
Completed
 
Locations

Bon Secours St. Francis Hospital

Greenville, United States, 29607

Status
Completed
 
Locations

Bata Hospital

Zlin, Czech Republic, 762 75

Status
Completed
 
Locations

Clatterbridge Centre for Oncology

Bebington, United Kingdom, CH63 4JY

Status
Completed
 
Locations

Comprehensive Cancer Centers of Nevada

Las Vegas, United States, 89169

Status
Completed
 
Locations

Sansum Clinic

Santa Barbara, United States, 93105

Status
Completed
 
Locations

University of Pittsburgh

Pittsburgh, United States, 15232

Status
Completed
 
Locations

Fudan University Shanghai Cancer Center

Shanghai, China, 200032

Status
Completed
 
Locations

Liaoning Cancer Hospital and Institute

Shengyang, China, 110042

Status
Completed
 
Locations

Jiangsu Cancer Hospital

Nanjing, China, 210009

Status
Completed
 
Locations

UF Cancer Center at Orlando Health

Orlando, United States, 32806

Status
Completed
 
Locations

First Affiliated Hospital of Guangzhou Medical University

Guangzhou, China

Status
Completed
 
Locations

FuJian Medical University Union Hospital

Fuzhou, China, 350001

Status
Completed
 
Locations

Huadong Hospital, Affiliated to Fudan University

Shanghai, China, 200040

Status
Completed
 
Locations

Fifth Medical Center, General Hospital of the Chinese People

Beijing, China, 100071

Status
Completed
 
Locations

Sun Yat-sen University Cancer Center

Guangzhou, China, 510060

Status
Completed
 
Locations

NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School

Nanjing, China, 210008

Status
Completed
 
Locations

Hubei Cancer Hospital

Wuhan, China, 430079

Status
Completed
 
Locations

Summit Cancer Center

Spokane, United States, 99208

Status
Completed
 
Locations

Rocky Mountain Cancer Centers

Littleton, United States, 80120-4413

Status
Completed
 
Locations

Texas Oncology-Denton South

Denton, United States, 76210

Status
Completed
 
Locations

Compass Oncology

Tigard, United States, 97223

Status
Completed
 

Trial Design