Carcinoma, Transitional Cell Clinical Trial
— FORT-1Official 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
Verified date | September 2022 |
Source | Bayer |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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 |
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 |
Lead Sponsor | Collaborator |
---|---|
Bayer |
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,
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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