Clinical trial NCT03410693: Study of Rogaratinib (BAY1163877) vs Chemotherapy in Patients With FGFR (Fibroblast Growth Factor Receptor)-Positive Locally Advanced or Metastatic Urothelial Carcinoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Carcinoma, Transitional Cell
Keywords: Urothelial carcinoma
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-01-25
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR) - Central Assessment
timeFrame: From start of treatment up to end of active follow-up, approximately 29 months
Secondary outcomes:
measure: Disease-control Rate (DCR) - Central Assessment
timeFrame: From start of treatment till end of active follow-up, approximately 29 months
measure: Progression-free Survival (PFS) - Central Assessment
timeFrame: From start of treatment till end of active follow-up, approximately 29 months
measure: Duration of Response (DOR) - Central Assessment
timeFrame: From start of treatment till end of active follow-up, approximately 29 months
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: From start of treatment up to 30 days after the last administration of study treatment, approximately 29 months
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Clinical Research Center, LLC
state: Alaska
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Littleton
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Orlando
country: United States
facility: UF Cancer Center at Orlando Health
state: Florida
city: Westwood
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Tigard
country: United States
facility: Compass Oncology
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Greenville
country: United States
facility: Bon Secours St. Francis Hospital
state: South Carolina
city: Denton
country: United States
facility: Texas Oncology-Denton South
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Spokane
country: United States
facility: Summit Cancer Center
state: Washington
city: Coffs Harbour
country: Australia
facility: Mid North Coast Cancer Institute
state: New South Wales
city: St Leonards
country: Australia
facility: Northern Cancer Institute
state: New South Wales
city: Sydney
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Wagga Wagga
country: Australia
facility: Riverina Cancer Care Centre
state: New South Wales
city: Wahroonga
country: Australia
facility: Sydney Adventist Hospital
state: New South Wales
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Krems
country: Austria
facility: Landesklinikum Krems
city: Wien
country: Austria
facility: Krankenhaus der Barmherzigen Brüder
city: Wien
country: Austria
facility: Universitätsklinikum AKH Wien
city: Wien
country: Austria
facility: Klinik Ottakring - Wilhelminenspital
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre
city: Toronto
country: Canada
facility: Princess Margaret Hospital-University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Sir Mortimer B. Davis Jewish General Hospital
state: Quebec
city: Ottawa
country: Canada
facility: Ottawa Hospital-General Campus
city: Fuzhou
country: China
facility: FuJian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Nanjing
country: China
facility: NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Shengyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Beijing
country: China
facility: Fifth Medical Center, General Hospital of the Chinese People
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangzhou Medical University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Huadong Hospital, Affiliated to Fudan University
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 4 - Krc
country: Czechia
facility: Fakultni Thomayerova Nemocnice
city: Zlin
country: Czechia
facility: Bata Hospital
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital, Skejby
city: Herlev
country: Denmark
facility: Herlev Hospital - Oncology Research Dept.
city: København
country: Denmark
facility: Rigshospitalet
city: Helsinki
country: Finland
facility: Docrates Klinikka
city: Besancon
country: France
facility: Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Hôpital Saint André - Bordeaux
city: Caen Cedex 5
country: France
facility: Centre de Lutte Contre le Cancer François Baclesse
city: Clermont Ferrand Cedex 1
country: France
facility: Centre Jean Perrin
city: Lille Cedex
country: France
facility: Centre Oscar Lambret - Lille
city: Lyon Cedex
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli-Calmettes - Marseille
city: Paris
country: France
facility: Cochin - Paris
city: Saint Mande
country: France
facility: Hôpital d'Instruction des Armées Begin
city: Strasbourg
country: France
facility: Clinique Saint Anne
city: Suresnes
country: France
facility: Centre Médico-Chirurgical Foch
city: Tübingen
country: Germany
facility: Eberhard-Karls-Universität Tübingen
state: Baden-Württemberg
city: Düsseldorf
country: Germany
facility: Heinrich-Heine-Universität Düsseldorf
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg Universität Mainz
state: Rheinland-Pfalz
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital Hong Kong
city: Budapest
country: Hungary
facility: MH Egeszsegugyi Kozpont
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: AMNCH
city: Haifa
country: Israel
facility: Rambam Health Corporation
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Hospital Ein Kerem
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petah Tikva
country: Israel
facility: Clalit Health Services Rabin Medical Center-Beilinson Campus
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Forlì Cesena
country: Italy
facility: IRST Istituto Scientifico Romagnolo per studio e cura tumori
state: Emilia-Romagna
city: Modena
country: Italy
facility: AUSL Modena
state: Emilia-Romagna
city: Modena
country: Italy
facility: A.O.U. di Modena - Policlinico
state: Emilia-Romagna
city: Roma
country: Italy
facility: A.O. San Camillo-Forlanini
state: Lazio
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: Lombardia
city: Milano
country: Italy
facility: IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)
state: Lombardia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
state: Lombardia
city: Torino
country: Italy
facility: A.O.U. San Luigi Gonzaga
state: Piemonte
city: Pisa
country: Italy
facility: A.O.U. Pisana
state: Toscana
city: Verona
country: Italy
facility: A.O.U.I. Verona
state: Veneto
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Hirosaki
country: Japan
facility: Hirosaki University Hospital
state: Aomori
city: Maebashi
country: Japan
facility: Gunma University Hospital
state: Gunma
city: Ota
country: Japan
facility: Gunma Prefectural Cancer Center
state: Gunma
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki
city: Morioka
country: Japan
facility: Iwate Medical University Hospital
state: Iwate
city: Yokohama
country: Japan
facility: Yokohama City University Hospital
state: Kanagawa
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Nippon Medical School Hospital
state: Tokyo
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Akita
country: Japan
facility: Akita University Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Niigata
country: Japan
facility: Niigata University Medical and Dental Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Toyama
country: Japan
facility: Toyama University Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka Lukaszczyka
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc
city: Poznan
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny UM we Wroclawiu
city: Loures
country: Portugal
facility: Hospital Beatriz Angelo
state: Lisboa
city: Coimbra
country: Portugal
facility: IPO Coimbra
city: Lisboa
country: Portugal
facility: Hospital CUF Infante Santo
city: Lisboa
country: Portugal
facility: CHULN - Hospital Santa Maria
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario do Porto
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Clinical Oncology Dispensary
city: Moscow
country: Russian Federation
facility: Moscow Scient. Res. Institute of Oncology n.a P.A. Hertzen
city: Nizhny Novgorod
country: Russian Federation
facility: Volga District Med Center FMBA
city: Omsk
country: Russian Federation
facility: Clinical Oncological Dispensary of Omsk Region
city: Ufa
country: Russian Federation
facility: Bashkir State Medical University
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Center Singapore
city: Bratislava
country: Slovakia
facility: Narodny onkologicky ustav
city: Nitra
country: Slovakia
facility: UROEXAM, spol. s r.o.
city: Poprad
country: Slovakia
facility: POKO Poprad s.r.o.
city: Badalona
country: Spain
facility: Institut Català d'Oncologia Badalona
state: Barcelona
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Català d'Oncologia Hospitalet
state: Barcelona
city: Palma de Mallorca
country: Spain
facility: Hospital Universitari Son Espases
state: Illes Baleares
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Ciutat Sanitària i Universitaria de la Vall d'Hebron
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Córdoba
country: Spain
facility: Hospital Reina Sofía
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Stockholm
country: Sweden
facility: Södersjukhuset
city: Stockholm
country: Sweden
facility: Karolinska Institutet
city: Basel
country: Switzerland
facility: Universitätsspital Basel
state: Basel-Stadt
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
state: Graubünden
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
state: Sankt Gallen
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital at Linkou
city: Bebington
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: Merseyside
city: London
country: United Kingdom
facility: Royal Marsden Hospital (London)
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Sternberg CN, Petrylak DP, Bellmunt J, Nishiyama H, Necchi A, Gurney H, Lee JL, van der Heijden MS, Rosenbaum E, Penel N, Pang ST, Li JR, Garcia Del Muro X, Joly F, Papai Z, Bao W, Ellinghaus P, Lu C, Sierecki M, Coppieters S, Nakajima K, Ishida TC, Quinn DI. FORT-1: Phase II/III Study of Rogaratinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Selected Based on FGFR1/3 mRNA Expression. J Clin Oncol. 2023 Jan 20;41(3):629-639. doi: 10.1200/JCO.21.02303. Epub 2022 Oct 14.
citation: Grunewald S, Politz O, Bender S, Heroult M, Lustig K, Thuss U, Kneip C, Kopitz C, Zopf D, Collin MP, Boemer U, Ince S, Ellinghaus P, Mumberg D, Hess-Stumpp H, Ziegelbauer K. Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models. Int J Cancer. 2019 Sep 1;145(5):1346-1357. doi: 10.1002/ijc.32224. Epub 2019 Mar 13.