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

NCT ID: NCT03410693

Last Updated: 2022-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 175 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-31
• Study Completion Date: 2020-10-27

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.

Conditions

Carcinoma, Transitional Cell

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rogaratinib

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".

Group Type: EXPERIMENTAL

Rogaratinib (BAY1163877)

Intervention Type: DRUG

Rogaratinib administered as oral (p.o.) tablets twice daily (b.i.d.) continuously

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".

Group Type: ACTIVE_COMPARATOR

Chemotherapy

Intervention Type: DRUG

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.

Interventions

Rogaratinib (BAY1163877)

Rogaratinib administered as oral (p.o.) tablets twice daily (b.i.d.) continuously

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Alaska Clinical Research Center, LLC

Anchorage, Alaska, United States

University of Arizona Cancer Center

Tucson, Arizona, United States

University of Southern California

Los Angeles, California, United States

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

Sansum Clinic

Santa Barbara, California, United States

Rocky Mountain Cancer Centers

Littleton, Colorado, United States

UF Cancer Center at Orlando Health

Orlando, Florida, United States

University of Kansas Medical Center

Westwood, Kansas, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Compass Oncology

Tigard, Oregon, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Bon Secours St. Francis Hospital

Greenville, South Carolina, United States

Texas Oncology-Denton South

Denton, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Summit Cancer Center

Spokane, Washington, 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

Sydney Adventist Hospital

Wahroonga, New South Wales, Australia

Pindara Private Hospital

Benowa, Queensland, Australia

Monash Medical Centre

Clayton, Victoria, Australia

Landesklinikum Krems

Krems, , Austria

Krankenhaus der Barmherzigen Brüder

Vienna, , Austria

Universitätsklinikum AKH Wien

Vienna, , Austria

Klinik Ottakring - Wilhelminenspital

Vienna, , Austria

UZ Gent

Ghent, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Clinique Saint-Pierre

Ottignies, , Belgium

Princess Margaret Hospital-University Health Network

Toronto, Ontario, Canada

Sir Mortimer B. Davis Jewish General Hospital

Montreal, Quebec, Canada

Ottawa Hospital-General Campus

Ottawa, , Canada

FuJian Medical University Union Hospital

Fuzhou, Fujian, China

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Hubei Cancer Hospital

Wuhan, Hubei, China

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

Nanjing, Jiangsu, China

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

First Affiliated Hospital of Guangzhou Medical University

Guangzhou, , China

Fudan University Shanghai Cancer Center

Shanghai, , China

Huadong Hospital, Affiliated to Fudan University

Shanghai, , China

Fakultni nemocnice Ostrava

Ostrava, , Czechia

Fakultni nemocnice Kralovske Vinohrady

Prague, , Czechia

Fakultni Thomayerova Nemocnice

Praha 4 - Krc, , Czechia

Bata Hospital

Zlín, , Czechia

Aarhus Universitetshospital, Skejby

Aarhus N, , Denmark

Rigshospitalet

Copenhagen, , Denmark

Herlev Hospital - Oncology Research Dept.

Herlev, , Denmark

Docrates Klinikka

Helsinki, , Finland

Hopital Jean Minjoz

Besançon, , France

Hôpital Saint André - Bordeaux

Bordeaux, , France

Centre de Lutte Contre le Cancer François Baclesse

Caen, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Centre Oscar Lambret - Lille

Lille, , France

Centre Léon Bérard

Lyon, , France

Institut Paoli-Calmettes - Marseille

Marseille, , France

Cochin - Paris

Paris, , France

Hôpital d'Instruction des Armées Begin

Saint-Mandé, , France

Clinique Saint Anne

Strasbourg, , France

Centre Médico-Chirurgical Foch

Suresnes, , France

Eberhard-Karls-Universität Tübingen

Tübingen, Baden-Wurttemberg, Germany

Heinrich-Heine-Universität Düsseldorf

Düsseldorf, North Rhine-Westphalia, Germany

Universitätsmedizin der Johannes Gutenberg Universität Mainz

Mainz, Rhineland-Palatinate, Germany

Prince of Wales Hospital Hong Kong

Shatin, , Hong Kong

MH Egeszsegugyi Kozpont

Budapest, , Hungary

Orszagos Onkologiai Intezet

Budapest, , Hungary

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, , Hungary

Cork University Hospital

Cork, , Ireland

AMNCH

Dublin, , Ireland

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, , Israel

IRST Istituto Scientifico Romagnolo per studio e cura tumori

Forlì Cesena, Emilia-Romagna, Italy

AUSL Modena

Modena, Emilia-Romagna, Italy

A.O.U. di Modena - Policlinico

Modena, Emilia-Romagna, Italy

A.O. San Camillo-Forlanini

Rome, Lazio, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, Italy

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

Milan, Lombardy, Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, Italy

A.O.U. San Luigi Gonzaga

Turin, Piedmont, Italy

A.O.U. Pisana

Pisa, Tuscany, Italy

A.O.U.I. Verona

Verona, Veneto, Italy

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

Hirosaki University Hospital

Hirosaki, Aomori, Japan

Gunma University Hospital

Maebashi, Gunma, Japan

Gunma Prefectural Cancer Center

Ōta, Gunma, Japan

Sapporo Medical University Hospital

Sapporo, Hokkaido, Japan

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Kobe City Medical Center General Hospital

Kobe, Hyōgo, Japan

University of Tsukuba Hospital

Tsukuba, Ibaraki, Japan

Iwate Medical University Hospital

Morioka, Iwate, Japan

Yokohama City University Hospital

Yokohama, Kanagawa, Japan

Kindai University Hospital

Sayama, Osaka, Japan

Saitama Medical University International Medical Center

Hidaka, Saitama, Japan

Nippon Medical School Hospital

Bunkyo-ku, Tokyo, Japan

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, Japan

Keio University Hospital

Shinjuku-ku, Tokyo, Japan

Akita University Hospital

Akita, , Japan

Kyushu University Hospital

Fukuoka, , Japan

Hiroshima City Hiroshima Citizens Hospital

Hiroshima, , Japan

Kumamoto University Hospital

Kumamoto, , Japan

Niigata University Medical and Dental Hospital

Niigata, , Japan

Osaka International Cancer Institute

Osaka, , Japan

Toyama University Hospital

Toyama, , Japan

Nederlands Kanker Instituut

Amsterdam, , Netherlands

Erasmus Medisch Centrum

Rotterdam, , Netherlands

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, , Poland

Hospital Beatriz Angelo

Loures, Lisbon District, Portugal

IPO Coimbra

Coimbra, , Portugal

Hospital CUF Infante Santo

Lisbon, , Portugal

CHULN - Hospital Santa Maria

Lisbon, , Portugal

Centro Hospitalar Universitario do Porto

Porto, , Portugal

Krasnoyarsk Regional Clinical Oncology Dispensary

Krasnoyarsk, , Russia

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

Moscow, , Russia

Volga District Med Center FMBA

Nizhny Novgorod, , Russia

Clinical Oncological Dispensary of Omsk Region

Omsk, , Russia

Bashkir State Medical University

Ufa, , Russia

National University Hospital

Singapore, , Singapore

National Cancer Center Singapore

Singapore, , Singapore

Narodny onkologicky ustav

Bratislava, , Slovakia

UROEXAM, spol. s r.o.

Nitra, , Slovakia

POKO Poprad s.r.o.

Poprad, , Slovakia

National Cancer Center

Goyang-si, Gyeonggido, South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Institut Català d'Oncologia Badalona

Badalona, Barcelona, Spain

Institut Català d'Oncologia Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitari Son Espases

Palma de Mallorca, Illes Baleares, Spain

Hospital del Mar

Barcelona, , Spain

Ciutat Sanitària i Universitaria de la Vall d'Hebron

Barcelona, , Spain

Hospital San Pedro de Alcántara

Cáceres, , Spain

Hospital Reina Sofía

Córdoba, , Spain

Hospital Ramón y Cajal

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Virgen de la Victoria

Málaga, , Spain

Instituto Valenciano de Oncología

Valencia, , Spain

Hospital General Universitario de Valencia

Valencia, , Spain

Södersjukhuset

Stockholm, , Sweden

Karolinska Institutet

Stockholm, , Sweden

Universitätsspital Basel

Basel, Canton of Basel-City, Switzerland

Kantonsspital St. Gallen

Sankt Gallen, Canton of St. Gallen, Switzerland

Kantonsspital Graubünden

Chur, Kanton Graubünden, Switzerland

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital at Linkou

Taoyuan District, , Taiwan

Clatterbridge Centre for Oncology

Bebington, Merseyside, United Kingdom

Royal Marsden Hospital (London)

London, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; China; Czechia; Denmark; Finland; France; Germany; Hong Kong; Hungary; Ireland; Israel; Italy; Japan; Netherlands; Poland; Portugal; Russia; Singapore; Slovakia; South Korea; Spain; Sweden; Switzerland; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36240478 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30807645 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

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Other Identifiers

2016-004340-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

17403

Identifier Type: -

Identifier Source: org_study_id