Study of Rogaratinib (BAY1163877) vs Chemotherapy in Patients With FGFR (Fibroblast Growth Factor Receptor)-Positive Locally Advanced or Metastatic Urothelial Carcinoma

Carcinoma, Transitional Cell Clinical Trial

— FORT-1  

Official title:

A Randomized, Open Label, Multicenter Phase 2/3 Study to Evaluate the Efficacy and Safety of Rogaratinib (BAY1163877) Compared to Chemotherapy in Patients With FGFR-positive Locally Advanced or Metastatic Urothelial Carcinoma Who Have Received Prior Platinum-containing Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03410693
• Other study ID #: 17403
• Secondary ID: 2016-004340-11
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: May 31, 2018
• Est. completion date: October 27, 2020

Study information

• Verified date: September 2022
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: October 27, 2020
• Est. primary completion date: October 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell

Intervention

Drug:
• Rogaratinib (BAY1163877)
Rogaratinib administered as oral (p.o.) tablets twice daily (b.i.d.) continuously
• Chemotherapy
Chemotherapy as taxane (docetaxel or paclitaxel) or vinflunine administered through intravenous (i.v.) infusion every 3 weeks (on day 1 of a 21-day cycle) The choice of the chemotherapy is at the discretion of the investigator, taking into consideration the status of the authorization or treatment guidelines in the given country.

Locations

Country	Name	City	State
Australia	Pindara Private Hospital	Benowa	Queensland
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Mid North Coast Cancer Institute	Coffs Harbour	New South Wales
Australia	Northern Cancer Institute	St Leonards	New South Wales
Australia	Macquarie University Hospital	Sydney	New South Wales
Australia	Riverina Cancer Care Centre	Wagga Wagga	New South Wales
Australia	Sydney Adventist Hospital	Wahroonga	New South Wales
Austria	Landesklinikum Krems	Krems
Austria	Klinik Ottakring - Wilhelminenspital	Wien
Austria	Krankenhaus der Barmherzigen Brüder	Wien
Austria	Universitätsklinikum AKH Wien	Wien
Belgium	UZ Gent	Gent
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	Clinique Saint-Pierre	Ottignies
Canada	Sir Mortimer B. Davis Jewish General Hospital	Montreal	Quebec
Canada	Ottawa Hospital-General Campus	Ottawa
Canada	Princess Margaret Hospital-University Health Network	Toronto	Ontario
China	Fifth Medical Center, General Hospital of the Chinese People	Beijing
China	FuJian Medical University Union Hospital	Fuzhou	Fujian
China	First Affiliated Hospital of Guangzhou Medical University	Guangzhou
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Jiangsu Cancer Hospital	Nanjing	Jiangsu
China	NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center	Shanghai
China	Huadong Hospital, Affiliated to Fudan University	Shanghai
China	Liaoning Cancer Hospital and Institute	Shengyang	Liaoning
China	Hubei Cancer Hospital	Wuhan	Hubei
Czechia	Fakultni nemocnice Ostrava	Ostrava
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
Czechia	Fakultni Thomayerova Nemocnice	Praha 4 - Krc
Czechia	Bata Hospital	Zlin
Denmark	Aarhus Universitetshospital, Skejby	Aarhus N
Denmark	Herlev Hospital - Oncology Research Dept.	Herlev
Denmark	Rigshospitalet	København
Finland	Docrates Klinikka	Helsinki
France	Hopital Jean Minjoz	Besancon
France	Hôpital Saint André - Bordeaux	Bordeaux
France	Centre de Lutte Contre le Cancer François Baclesse	Caen Cedex 5
France	Centre Jean Perrin	Clermont Ferrand Cedex 1
France	Centre Oscar Lambret - Lille	Lille Cedex
France	Centre Léon Bérard	Lyon Cedex
France	Institut Paoli-Calmettes - Marseille	Marseille
France	Cochin - Paris	Paris
France	Hôpital d'Instruction des Armées Begin	Saint Mande
France	Clinique Saint Anne	Strasbourg
France	Centre Médico-Chirurgical Foch	Suresnes
Germany	Heinrich-Heine-Universität Düsseldorf	Düsseldorf	Nordrhein-Westfalen
Germany	Universitätsmedizin der Johannes Gutenberg Universität Mainz	Mainz	Rheinland-Pfalz
Germany	Eberhard-Karls-Universität Tübingen	Tübingen	Baden-Württemberg
Hong Kong	Prince of Wales Hospital Hong Kong	Shatin
Hungary	MH Egeszsegugyi Kozpont	Budapest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont	Pecs
Ireland	Cork University Hospital	Cork
Ireland	AMNCH	Dublin
Israel	Rambam Health Corporation	Haifa
Israel	Hadassah Hebrew University Hospital Ein Kerem	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Clalit Health Services Rabin Medical Center-Beilinson Campus	Petah Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Italy	IRST Istituto Scientifico Romagnolo per studio e cura tumori	Forlì Cesena	Emilia-Romagna
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano	Lombardia
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia
Italy	IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)	Milano	Lombardia
Italy	A.O.U. di Modena - Policlinico	Modena	Emilia-Romagna
Italy	AUSL Modena	Modena	Emilia-Romagna
Italy	A.O.U. Pisana	Pisa	Toscana
Italy	A.O. San Camillo-Forlanini	Roma	Lazio
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma	Lazio
Italy	A.O.U. San Luigi Gonzaga	Torino	Piemonte
Italy	A.O.U.I. Verona	Verona	Veneto
Japan	Akita University Hospital	Akita
Japan	Nippon Medical School Hospital	Bunkyo-ku	Tokyo
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	Kyushu University Hospital	Fukuoka
Japan	Saitama Medical University International Medical Center	Hidaka	Saitama
Japan	Hirosaki University Hospital	Hirosaki	Aomori
Japan	Hiroshima City Hiroshima Citizens Hospital	Hiroshima
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	The Cancer Institute Hospital of JFCR	Koto-ku	Tokyo
Japan	Kumamoto University Hospital	Kumamoto
Japan	Gunma University Hospital	Maebashi	Gunma
Japan	Iwate Medical University Hospital	Morioka	Iwate
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Niigata University Medical and Dental Hospital	Niigata
Japan	Osaka International Cancer Institute	Osaka
Japan	Kindai University Hospital	Osakasayama	Osaka
Japan	Gunma Prefectural Cancer Center	Ota	Gunma
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Sapporo Medical University Hospital	Sapporo	Hokkaido
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Japan	Toyama University Hospital	Toyama
Japan	University of Tsukuba Hospital	Tsukuba	Ibaraki
Japan	Yokohama City University Hospital	Yokohama	Kanagawa
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggido
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Netherlands	Nederlands Kanker Instituut	Amsterdam
Netherlands	Erasmus Medisch Centrum	Rotterdam
Poland	Centrum Onkologii im. Prof. Franciszka Lukaszczyka	Bydgoszcz
Poland	Swietokrzyskie Centrum Onkologii	Kielce
Poland	Przychodnia Lekarska KOMED	Konin
Poland	Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc	Olsztyn
Poland	Szpital Kliniczny Przemienienia Panskiego	Poznan
Poland	Uniwersytecki Szpital Kliniczny UM we Wroclawiu	Wroclaw
Portugal	IPO Coimbra	Coimbra
Portugal	CHULN - Hospital Santa Maria	Lisboa
Portugal	Hospital CUF Infante Santo	Lisboa
Portugal	Hospital Beatriz Angelo	Loures	Lisboa
Portugal	Centro Hospitalar Universitario do Porto	Porto
Russian Federation	Krasnoyarsk Regional Clinical Oncology Dispensary	Krasnoyarsk
Russian Federation	Moscow Scient. Res. Institute of Oncology n.a P.A. Hertzen	Moscow
Russian Federation	Volga District Med Center FMBA	Nizhny Novgorod
Russian Federation	Clinical Oncological Dispensary of Omsk Region	Omsk
Russian Federation	Bashkir State Medical University	Ufa
Singapore	National Cancer Center Singapore	Singapore
Singapore	National University Hospital	Singapore
Slovakia	Narodny onkologicky ustav	Bratislava
Slovakia	UROEXAM, spol. s r.o.	Nitra
Slovakia	POKO Poprad s.r.o.	Poprad
Spain	Institut Català d'Oncologia Badalona	Badalona	Barcelona
Spain	Ciutat Sanitària i Universitaria de la Vall d'Hebron	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital San Pedro de Alcántara	Cáceres
Spain	Hospital Reina Sofía	Córdoba
Spain	Institut Català d'Oncologia Hospitalet	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Virgen de la Victoria	Málaga
Spain	Hospital Universitari Son Espases	Palma de Mallorca	Illes Baleares
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Instituto Valenciano de Oncología	Valencia
Sweden	Karolinska Institutet	Stockholm
Sweden	Södersjukhuset	Stockholm
Switzerland	Universitätsspital Basel	Basel	Basel-Stadt
Switzerland	Kantonsspital Graubünden	Chur	Graubünden
Switzerland	Kantonsspital St. Gallen	St. Gallen	Sankt Gallen
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital at Linkou	Taoyuan
United Kingdom	Clatterbridge Centre for Oncology	Bebington	Merseyside
United Kingdom	Royal Marsden Hospital (London)	London
United States	Alaska Clinical Research Center, LLC	Anchorage	Alaska
United States	Texas Oncology-Denton South	Denton	Texas
United States	Bon Secours St. Francis Hospital	Greenville	South Carolina
United States	Houston Methodist Hospital	Houston	Texas
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Rocky Mountain Cancer Centers	Littleton	Colorado
United States	University of Southern California	Los Angeles	California
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Sansum Clinic	Santa Barbara	California
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Summit Cancer Center	Spokane	Washington
United States	Compass Oncology	Tigard	Oregon
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	University of Kansas Medical Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  Czechia,  Denmark,  Finland,  France,  Germany,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Portugal,  Russian Federation,  Singapore,  Slovakia,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) - Central Assessment	ORR is defined as the percentage of participants with complete response (CR) or partial response (PR). participants for whom overall best response is not CR or PR, as well as participants without any post-baseline tumor assessment will be considered non-responders.	From start of treatment up to end of active follow-up, approximately 29 months
Secondary	Disease-control Rate (DCR) - Central Assessment	DCR was defined as the percentage of participants whose overall best response was not a progressive disease (i.e., CR, PR, stable disease [SD] or Non CR/Non PD).	From start of treatment till end of active follow-up, approximately 29 months
Secondary	Progression-free Survival (PFS) - Central Assessment	Progression free survival (PFS) was defined as the time (days) from randomization to date of first observed disease progression (radiological or clinical assessment or both) or death due to any cause (if death occurred before progression was documented).	From start of treatment till end of active follow-up, approximately 29 months
Secondary	Duration of Response (DOR) - Central Assessment	DOR (for patients with PR and CR only) was defined as the time from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression (including symptomatic deterioration) or death, whichever was earlier	From start of treatment till end of active follow-up, approximately 29 months
Secondary	Number of Participants With Treatment Emergent Adverse Events	A treatment-emergent event was defined as any event arising or worsening after the start of study drug administration until 30 days after the last administration of study treatment	From start of treatment up to 30 days after the last administration of study treatment, approximately 29 months

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