Study of Rogaratinib (BAY1163877) vs Chemotherapy in Patients With FGFR (Fibroblast Growth Factor Receptor)-Positive Locally Advanced or Metastatic Urothelial Carcinoma
- Conditions
- Carcinoma, Transitional Cell
- Interventions
- Drug: Rogaratinib (BAY1163877)Drug: Chemotherapy
- Registration Number
- NCT03410693
- Lead Sponsor
- Bayer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 175
-
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
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rogaratinib Rogaratinib (BAY1163877) Rogaratinib treatment study arm, comprising 1. Pre-treatment period, including FGFR testing and screening, 2. Treatment period, and 3. Follow-up period, including active follow-up and long-term follow-up. Patients will be considered "on study" during the pre-treatment, treatment and active followup periods. During the long-term follow-up period the patients will be considered "off study". Chemotherapy Chemotherapy Chemotherapy treatment study arm, comprising 1. Pre-treatment period, including FGFR testing and screening, 2. Treatment period, and 3. Follow-up period, including active follow-up and long-term follow-up. Patients will be considered "on study" during the pre-treatment, treatment and active followup periods. During the long-term follow-up period the patients will be considered "off study".
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) - Central Assessment From start of treatment up to end of active follow-up, approximately 29 months 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) - Central Assessment From start of treatment till end of active follow-up, approximately 29 months 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
Number of Participants With Treatment Emergent Adverse Events From start of treatment up to 30 days after the last administration of study treatment, approximately 29 months 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
Progression-free Survival (PFS) - Central Assessment From start of treatment till end of active follow-up, approximately 29 months 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).
Disease-control Rate (DCR) - Central Assessment From start of treatment till end of active follow-up, approximately 29 months 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).
Trial Locations
- Locations (161)
Summit Cancer Center
🇺🇸Spokane, Washington, United States
Princess Margaret Hospital-University Health Network
🇨🇦Toronto, Ontario, Canada
Jiangsu Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
Liaoning Cancer Hospital and Institute
🇨🇳Shengyang, Liaoning, China
Fifth Medical Center, General Hospital of the Chinese People
🇨🇳Beijing, China
Huadong Hospital, Affiliated to Fudan University
🇨🇳Shanghai, China
Fakultni Thomayerova Nemocnice
🇨🇿Praha 4 - Krc, Czechia
Bata Hospital
🇨🇿Zlin, Czechia
Herlev Hospital - Oncology Research Dept.
🇩🇰Herlev, Denmark
Centre Jean Perrin
🇫🇷Clermont Ferrand Cedex 1, France
Institut Paoli-Calmettes - Marseille
🇫🇷Marseille, France
Hôpital d'Instruction des Armées Begin
🇫🇷Saint Mande, France
Clinique Saint Anne
🇫🇷Strasbourg, France
Eberhard-Karls-Universität Tübingen
🇩🇪Tübingen, Baden-Württemberg, Germany
Heinrich-Heine-Universität Düsseldorf
🇩🇪Düsseldorf, Nordrhein-Westfalen, Germany
Universitätsmedizin der Johannes Gutenberg Universität Mainz
🇩🇪Mainz, Rheinland-Pfalz, Germany
Pecsi Tudomanyegyetem Klinikai Kozpont
🇭🇺Pecs, Hungary
Cork University Hospital
🇮🇪Cork, Ireland
Keio University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Krasnoyarsk Regional Clinical Oncology Dispensary
🇷🇺Krasnoyarsk, Russian Federation
Clinical Oncological Dispensary of Omsk Region
🇷🇺Omsk, Russian Federation
Ciutat Sanitària i Universitaria de la Vall d'Hebron
🇪🇸Barcelona, Spain
Institut Català d'Oncologia Hospitalet
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Reina Sofía
🇪🇸Córdoba, Spain
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Clatterbridge Centre for Oncology
🇬🇧Bebington, Merseyside, United Kingdom
University of Southern California
🇺🇸Los Angeles, California, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Universitätsspital Basel
🇨🇭Basel, Basel-Stadt, Switzerland
Kantonsspital Graubünden
🇨🇭Chur, Graubünden, Switzerland
Aarhus Universitetshospital, Skejby
🇩🇰Aarhus N, Denmark
AMNCH
🇮🇪Dublin, Ireland
Hiroshima City Hiroshima Citizens Hospital
🇯🇵Hiroshima, Japan
UC Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Sansum Clinic
🇺🇸Santa Barbara, California, United States
UF Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Texas Oncology-Denton South
🇺🇸Denton, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
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
Pindara Private Hospital
🇦🇺Benowa, Queensland, Australia
Landesklinikum Krems
🇦🇹Krems, Austria
Ottawa Hospital-General Campus
🇨🇦Ottawa, Canada
Clinique Saint-Pierre
🇧🇪Ottignies, Belgium
FuJian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, China
NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School
🇨🇳Nanjing, Jiangsu, China
Hubei Cancer Hospital
🇨🇳Wuhan, Hubei, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czechia
Rigshospitalet
🇩🇰København, Denmark
Hôpital Saint André - Bordeaux
🇫🇷Bordeaux, France
Hopital Jean Minjoz
🇫🇷Besancon, France
Centre de Lutte Contre le Cancer François Baclesse
🇫🇷Caen Cedex 5, France
Centre Oscar Lambret - Lille
🇫🇷Lille Cedex, France
Centre Léon Bérard
🇫🇷Lyon Cedex, France
Cochin - Paris
🇫🇷Paris, France
Centre Médico-Chirurgical Foch
🇫🇷Suresnes, France
MH Egeszsegugyi Kozpont
🇭🇺Budapest, Hungary
Rambam Health Corporation
🇮🇱Haifa, Israel
Meir Medical Center
🇮🇱Kfar Saba, Israel
Clalit Health Services Rabin Medical Center-Beilinson Campus
🇮🇱Petah Tikva, Israel
AUSL Modena
🇮🇹Modena, Emilia-Romagna, Italy
IRST Istituto Scientifico Romagnolo per studio e cura tumori
🇮🇹Forlì Cesena, Emilia-Romagna, Italy
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
A.O.U. di Modena - Policlinico
🇮🇹Modena, Emilia-Romagna, Italy
A.O. San Camillo-Forlanini
🇮🇹Roma, Lazio, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Lombardia, Italy
IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)
🇮🇹Milano, Lombardia, Italy
Nagoya University Hospital
🇯🇵Nagoya, Aichi, Japan
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Lombardia, Italy
Gunma Prefectural Cancer Center
🇯🇵Ota, Gunma, Japan
A.O.U. San Luigi Gonzaga
🇮🇹Torino, Piemonte, Italy
A.O.U. Pisana
🇮🇹Pisa, Toscana, Italy
Gunma University Hospital
🇯🇵Maebashi, Gunma, Japan
Sapporo Medical University Hospital
🇯🇵Sapporo, Hokkaido, Japan
University of Tsukuba Hospital
🇯🇵Tsukuba, Ibaraki, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe, Hyogo, Japan
Kindai University Hospital
🇯🇵Osakasayama, Osaka, Japan
Akita University Hospital
🇯🇵Akita, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Niigata University Medical and Dental Hospital
🇯🇵Niigata, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Toyama University Hospital
🇯🇵Toyama, Japan
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Nederlands Kanker Instituut
🇳🇱Amsterdam, Netherlands
Centrum Onkologii im. Prof. Franciszka Lukaszczyka
🇵🇱Bydgoszcz, Poland
Przychodnia Lekarska KOMED
🇵🇱Konin, Poland
Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc
🇵🇱Olsztyn, Poland
Uniwersytecki Szpital Kliniczny UM we Wroclawiu
🇵🇱Wroclaw, Poland
Szpital Kliniczny Przemienienia Panskiego
🇵🇱Poznan, Poland
Hospital Beatriz Angelo
🇵🇹Loures, Lisboa, Portugal
Hospital CUF Infante Santo
🇵🇹Lisboa, Portugal
IPO Coimbra
🇵🇹Coimbra, Portugal
CHULN - Hospital Santa Maria
🇵🇹Lisboa, Portugal
Centro Hospitalar Universitario do Porto
🇵🇹Porto, Portugal
Volga District Med Center FMBA
🇷🇺Nizhny Novgorod, Russian Federation
Moscow Scient. Res. Institute of Oncology n.a P.A. Hertzen
🇷🇺Moscow, Russian Federation
Bashkir State Medical University
🇷🇺Ufa, Russian Federation
UROEXAM, spol. s r.o.
🇸🇰Nitra, Slovakia
National University Hospital
🇸🇬Singapore, Singapore
National Cancer Center Singapore
🇸🇬Singapore, Singapore
Narodny onkologicky ustav
🇸🇰Bratislava, Slovakia
Institut Català d'Oncologia Badalona
🇪🇸Badalona, Barcelona, Spain
Hospital Universitari Son Espases
🇪🇸Palma de Mallorca, Illes Baleares, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Hospital San Pedro de Alcántara
🇪🇸Cáceres, Spain
Hospital Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
Södersjukhuset
🇸🇪Stockholm, Sweden
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Karolinska Institutet
🇸🇪Stockholm, Sweden
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Royal Marsden Hospital (London)
🇬🇧London, United Kingdom
Chang Gung Memorial Hospital at Linkou
🇨🇳Taoyuan, Taiwan
Fakultni nemocnice Ostrava
🇨🇿Ostrava, Czechia
Sydney Adventist Hospital
🇦🇺Wahroonga, New South Wales, Australia
Krankenhaus der Barmherzigen Brüder
🇦🇹Wien, Austria
Klinik Ottakring - Wilhelminenspital
🇦🇹Wien, Austria
Rocky Mountain Cancer Centers
🇺🇸Littleton, Colorado, United States
Hadassah Hebrew University Hospital Ein Kerem
🇮🇱Jerusalem, Israel
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Lazio, Italy
Docrates Klinikka
🇫🇮Helsinki, Finland
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
A.O.U.I. Verona
🇮🇹Verona, Veneto, Italy
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
UZ Gent
🇧🇪Gent, Belgium
Hirosaki University Hospital
🇯🇵Hirosaki, Aomori, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Iwate Medical University Hospital
🇯🇵Morioka, Iwate, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Koto-ku, Tokyo, Japan
Compass Oncology
🇺🇸Tigard, Oregon, United States
Alaska Clinical Research Center, LLC
🇺🇸Anchorage, Alaska, United States
Bon Secours St. Francis Hospital
🇺🇸Greenville, South Carolina, United States
Universitätsklinikum AKH Wien
🇦🇹Wien, Austria
Sir Mortimer B. Davis Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Yokohama City University Hospital
🇯🇵Yokohama, Kanagawa, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Swietokrzyskie Centrum Onkologii
🇵🇱Kielce, Poland
POKO Poprad s.r.o.
🇸🇰Poprad, Slovakia
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Orszagos Onkologiai Intezet
🇭🇺Budapest, Hungary
Saitama Medical University International Medical Center
🇯🇵Hidaka, Saitama, Japan
National Cancer Center
🇰🇷Goyang-si, Gyeonggido, Korea, Republic of
Nippon Medical School Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Kantonsspital St. Gallen
🇨🇭St. Gallen, Sankt Gallen, Switzerland
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
University of Kansas Medical Center
🇺🇸Westwood, Kansas, United States
Prince of Wales Hospital Hong Kong
🇭🇰Shatin, Hong Kong