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

NCT03410693 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 174032016-004340-11
• Study Type: interventional
• Target: 175
• Locations: 28 countries
• Sites: 154

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

Keywords

Urothelial carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Disease-control Rate (DCR) - Central Assessment

  From start of treatment till end of active follow-up, approximately 29 months

• Progression-free Survival (PFS) - Central Assessment

  From start of treatment till end of active follow-up, approximately 29 months

• Duration of Response (DOR) - Central Assessment

  From start of treatment till end of active follow-up, approximately 29 months

• 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

Study Arms (2)

Rogaratinib

EXPERIMENTAL

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".

Drug: Rogaratinib (BAY1163877)

Chemotherapy

ACTIVE COMPARATOR

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".

Drug: Chemotherapy

Interventions

Rogaratinib (BAY1163877) DRUG

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

Rogaratinib

Chemotherapy 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.

Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (161)

Alaska Clinical Research Center, LLC

Anchorage, Alaska, 99503, United States

Location

University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Sansum Clinic

Santa Barbara, California, 93105, United States

Location

Rocky Mountain Cancer Centers

Littleton, Colorado, 80120-4413, United States

Location

UF Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Compass Oncology

Tigard, Oregon, 97223, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

Bon Secours St. Francis Hospital

Greenville, South Carolina, 29607, United States

Location

Texas Oncology-Denton South

Denton, Texas, 76210, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030-2707, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Summit Cancer Center

Spokane, Washington, 99208, United States

Location

Mid North Coast Cancer Institute

Coffs Harbour, New South Wales, 2450, Australia

Location

Northern Cancer Institute

St Leonards, New South Wales, 2065, Australia

Location

Macquarie University Hospital

Sydney, New South Wales, 2109, Australia

Location

Riverina Cancer Care Centre

Wagga Wagga, New South Wales, 2650, Australia

Location

Sydney Adventist Hospital

Wahroonga, New South Wales, 2076, Australia

Location

Pindara Private Hospital

Benowa, Queensland, 4217, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Landesklinikum Krems

Krems, 3500, Austria

Location

Krankenhaus der Barmherzigen Brüder

Vienna, 1020, Austria

Location

Universitätsklinikum AKH Wien

Vienna, 1090, Austria

Location

Klinik Ottakring - Wilhelminenspital

Vienna, 1160, Austria

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Clinique Saint-Pierre

Ottignies, 1340, Belgium

Location

Princess Margaret Hospital-University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Sir Mortimer B. Davis Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Ottawa Hospital-General Campus

Ottawa, K1H 8L6, Canada

Location

FuJian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

Location

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

Nanjing, Jiangsu, 210008, China

Location

Jiangsu Cancer Hospital

Nanjing, Jiangsu, 210009, China

Location

Liaoning Cancer Hospital and Institute

Shengyang, Liaoning, 110042, China

Location

Fifth Medical Center, General Hospital of the Chinese People

Beijing, 100071, China

Location

First Affiliated Hospital of Guangzhou Medical University

Guangzhou, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Huadong Hospital, Affiliated to Fudan University

Shanghai, 200040, China

Location

Fakultni nemocnice Ostrava

Ostrava, 708 52, Czechia

Location

Fakultni nemocnice Kralovske Vinohrady

Prague, 10034, Czechia

Location

Fakultni Thomayerova Nemocnice

Praha 4 - Krc, 140 59, Czechia

Location

Bata Hospital

Zlín, 762 75, Czechia

Location

Aarhus Universitetshospital, Skejby

Aarhus N, 8200, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Herlev Hospital - Oncology Research Dept.

Herlev, 2730, Denmark

Location

Docrates Klinikka

Helsinki, 00180, Finland

Location

Hopital Jean Minjoz

Besançon, 25030, France

Location

Hôpital Saint André - Bordeaux

Bordeaux, 33000, France

Location

Centre de Lutte Contre le Cancer François Baclesse

Caen, 14076, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Oscar Lambret - Lille

Lille, 59020, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Institut Paoli-Calmettes - Marseille

Marseille, 13273, France

Location

Cochin - Paris

Paris, 75674, France

Location

Hôpital d'Instruction des Armées Begin

Saint-Mandé, 94160, France

Location

Clinique Saint Anne

Strasbourg, 67000, France

Location

Centre Médico-Chirurgical Foch

Suresnes, 92151, France

Location

Eberhard-Karls-Universität Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Heinrich-Heine-Universität Düsseldorf

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Universitätsmedizin der Johannes Gutenberg Universität Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Prince of Wales Hospital Hong Kong

Shatin, Hong Kong

Location

MH Egeszsegugyi Kozpont

Budapest, 1062, Hungary

Location

Orszagos Onkologiai Intezet

Budapest, 1122, Hungary

Location

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, 7624, Hungary

Location

Cork University Hospital

Cork, Ireland

Location

AMNCH

Dublin, 24, Ireland

Location

Rambam Health Corporation

Haifa, 3109601, Israel

Location

Hadassah Hebrew University Hospital Ein Kerem

Jerusalem, 9112001, Israel

Location

Meir Medical Center

Kfar Saba, 4428164, Israel

Location

Clalit Health Services Rabin Medical Center-Beilinson Campus

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 5266202, Israel

Location

IRST Istituto Scientifico Romagnolo per studio e cura tumori

Forlì Cesena, Emilia-Romagna, 47014, Italy

Location

AUSL Modena

Modena, Emilia-Romagna, 41012, Italy

Location

A.O.U. di Modena - Policlinico

Modena, Emilia-Romagna, 41124, Italy

Location

A.O. San Camillo-Forlanini

Rome, Lazio, 00152, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, 00168, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy

Location

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

Milan, Lombardy, 20141, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, 20162, Italy

Location

A.O.U. San Luigi Gonzaga

Turin, Piedmont, 10043, Italy

Location

A.O.U. Pisana

Pisa, Tuscany, 56126, Italy

Location

A.O.U.I. Verona

Verona, Veneto, 37134, Italy

Location

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

Hirosaki University Hospital

Hirosaki, Aomori, 036-8563, Japan

Location

Gunma University Hospital

Maebashi, Gunma, 371-8511, Japan

Location

Gunma Prefectural Cancer Center

Ōta, Gunma, 373-8550, Japan

Location

Sapporo Medical University Hospital

Sapporo, Hokkaido, 060-8543, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Kobe City Medical Center General Hospital

Kobe, Hyōgo, 650-0047, Japan

Location

University of Tsukuba Hospital

Tsukuba, Ibaraki, 305-8576, Japan

Location

Iwate Medical University Hospital

Morioka, Iwate, 028-3695, Japan

Location

Yokohama City University Hospital

Yokohama, Kanagawa, 236-0004, Japan

Location

Kindai University Hospital

Sayama, Osaka, 589-8511, Japan

Location

Saitama Medical University International Medical Center

Hidaka, Saitama, 350-1298, Japan

Location

Nippon Medical School Hospital

Bunkyo-ku, Tokyo, 113-8603, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, 135-8550, Japan

Location

Keio University Hospital

Shinjuku-ku, Tokyo, 160-8582, Japan

Location

Akita University Hospital

Akita, 010-8543, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Hiroshima City Hiroshima Citizens Hospital

Hiroshima, 730-8518, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

Niigata University Medical and Dental Hospital

Niigata, 951-8520, Japan

Location

Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

Toyama University Hospital

Toyama, 930-0194, Japan

Location

Nederlands Kanker Instituut

Amsterdam, 1066 CX, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3075 EA, Netherlands

Location

Centrum Onkologii im. Prof. Franciszka Lukaszczyka

Bydgoszcz, 85-796, Poland

Location

Swietokrzyskie Centrum Onkologii

Kielce, 25-734, Poland

Location

Przychodnia Lekarska KOMED

Konin, 62-500, Poland

Location

Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc

Olsztyn, 10-357, Poland

Location

Szpital Kliniczny Przemienienia Panskiego

Poznan, 60-569, Poland

Location

Uniwersytecki Szpital Kliniczny UM we Wroclawiu

Wroclaw, 50-556, Poland

Location

Hospital Beatriz Angelo

Loures, Lisbon District, 2674-514, Portugal

Location

IPO Coimbra

Coimbra, 3000-075, Portugal

Location

Hospital CUF Infante Santo

Lisbon, 1350-070, Portugal

Location

CHULN - Hospital Santa Maria

Lisbon, 1649-035, Portugal

Location

Centro Hospitalar Universitario do Porto

Porto, 4099-001, Portugal

Location

Krasnoyarsk Regional Clinical Oncology Dispensary

Krasnoyarsk, 660133, Russia

Location

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

Moscow, 125284, Russia

Location

Volga District Med Center FMBA

Nizhny Novgorod, 603109, Russia

Location

Clinical Oncological Dispensary of Omsk Region

Omsk, 644013, Russia

Location

Bashkir State Medical University

Ufa, 450008, Russia

Location

National University Hospital

Singapore, 119074, Singapore

Location

National Cancer Center Singapore

Singapore, 169610, Singapore

Location

Narodny onkologicky ustav

Bratislava, 833 10, Slovakia

Location

UROEXAM, spol. s r.o.

Nitra, 949 01, Slovakia

Location

POKO Poprad s.r.o.

Poprad, 085 01, Slovakia

Location

National Cancer Center

Goyang-si, Gyeonggido, 10408, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Institut Català d'Oncologia Badalona

Badalona, Barcelona, 08916, Spain

Location

Institut Català d'Oncologia Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitari Son Espases

Palma de Mallorca, Illes Baleares, 07120, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Ciutat Sanitària i Universitaria de la Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, 10003, Spain

Location

Hospital Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Virgen de la Victoria

Málaga, 29010, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Södersjukhuset

Stockholm, 118 83, Sweden

Location

Karolinska Institutet

Stockholm, 17167, Sweden

Location

Universitätsspital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

Kantonsspital Graubünden

Chur, Kanton Graubünden, 7000, Switzerland

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital at Linkou

Taoyuan District, 33305, Taiwan

Location

Clatterbridge Centre for Oncology

Bebington, Merseyside, CH63 4JY, United Kingdom

Location

Royal Marsden Hospital (London)

London, SW3 6JJ, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 36240478 DERIVED

• 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.

  PMID: 30807645 DERIVED

Related Links

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MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

Rogaratinib; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2018
• First Posted: January 25, 2018
• Study Start: May 31, 2018
• Primary Completion: October 27, 2020
• Study Completion: October 27, 2020
• Last Updated: September 28, 2022
• Results First Posted: December 29, 2021

Record last verified: 2022-09

Locations

PL (6); HU (3); CH (3); DK (3); JP (23); CZ (4); AU (4); US (16); CA (3); NL (2); FI (1); KR (4); FR (11); SL (3); IE (2); SE (2); IT (11); GB (2); RU (5); TW (5); HK (1); DE (3); ES (12); CN (10); BE (3); SG (2); IL (5); PT (5)