A Phase 2, Two-arm Multicenter, Open-Label Study to Determine the Efficacy and the Safety of Two Different Dose Regimens of a Pan-FGFR Tyrosine Kinase Inhibitor JNJ-42756493 in Subjects With Metastatic or Surgically Unresectable Urothelial Cancer With FGFR Genomic Alterations


Condition: Urothelial Cancer

Intervention:

  • Drug: JNJ-42756493

Purpose: The purpose of this study is to evaluate the objective response rate (complete response [CR]+ partial response [PR]) of the selected dose regimen in participants with metastatic or surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02365597

Sponsor: Janssen Research & Development, LLC

Primary Outcome Measures:

  • Measure: Percentage of Participants with Best Overall Response
  • Time Frame: 1 year
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Progression-free survival
  • Time Frame: From the date of the first dose of study drug until disease progression or death as assessed up to the last efficacy assessment for disease progression (approximately 3 years 9 months)
  • Safety Issue:
  • Measure: Duration of Response
  • Time Frame: From the date of the first dose of study drug until disease progression or death as assessed up to the last efficacy assessment for disease progression (approximately 3 years 9 months)
  • Safety Issue:
  • Measure: Overall survival
  • Time Frame: From the date of the first dose of study drug until death (up to 3 years 9 months)
  • Safety Issue:
  • Measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
  • Time Frame: Screening up to end of study (approximately 3 years 9 months)
  • Safety Issue:
  • Measure: Percentage of Participants With Biomarker Assessment
  • Time Frame: Baseline up to end of study (approximately 3 years 9 months)
  • Safety Issue:
  • Measure: Plasma Concentration of JNJ 42756493
  • Time Frame: Baseline up to end of study (approximately 3 years 9 months)
  • Safety Issue:
  • Measure: Plasma Clearance of JNJ 42756493
  • Time Frame: Baseline up to end of study (approximately 3 years 9 months)
  • Safety Issue:
  • Measure: Volume of Distribution of JNJ 42756493
  • Time Frame: Baseline up to end of study (approximately 3 years 9 months)
  • Safety Issue:

Estimated Enrollment: 210

Study Start Date: April 22, 2015

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Must have histologic demonstration of metastatic or surgically unresectable urothelial cancer. Minor components of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
  • Must have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1, or 2
  • Must have adequate bone marrow, liver, and renal function as described in protocol
  • Negative pregnancy test (urine or serum beta human chorionic gonadotropin [b-hCG]) at Screening for women of child bearing potential who are sexually active
  • Must have shown disease progression according to RECIST, version 1.1, following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Subjects who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression according to RECIST, version 1.1, within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting. These subjects will be referred to as chemo-refractory subjects. (Subjects who have shown disease progression according to RECIST, version 1.1 following prior treatment with anti-Programmed death-ligand 1 (anti PDL1/PD1) antibodies are also eligible)

Exclusion Criteria:

  • Received chemotherapy, targeted therapies, definitive radiotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and mitomycin C, within 6 weeks; in the case of immunotherapy, within 4 weeks) before the first administration of study drug. Localized palliative radiation therapy (but should not include radiation to target lesions) and ongoing bisphosphonates and denosumab, are permitted
  • Has persistent phosphate level greater than upper limit of normal (ULN) during screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical management
  • Has a history of or current uncontrolled cardiovascular disease
  • Females who are pregnant, breast-feeding, or planning to become pregnant within 3 months after the last dose of study drug and males who plan to father a child while enrolled in this study or within 5 months after the last dose of study drug
  • Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, or Grade 1 neuropathy)

Contact:

  • Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:

Locations:

  • Mayo Clinic Arizona
  • Scottsdale Arizona 85259 United States
  • Arizona Oncology Associates, PC - NAHOA
  • Sedona Arizona 86336 United States
  • University of Arizona Cancer Center
  • Tucson Arizona 85724 United States
  • Marin Cancer Care Inc.
  • Greenbrae California 94904 United States
  • Cedars Sinai Medical Center - Pediatric Infectious Disease
  • Los Angeles California 90048 United States
  • Ronald Reagan UCLA Medical Center
  • Los Angeles California 90095 United States
  • University of California - Davis Medical Center
  • Sacramento California 95817 United States
  • Stanford University Medical Center
  • Stanford California 94305 United States
  • Rocky Mountain Cancer Center
  • Aurora Colorado 80012 United States
  • Georgetown Univ. Medical Center - Lombardi Cancer Center
  • Washington District of Columbia 20007 United States
  • Northwestern University Feinberg School of Medicine
  • Chicago Illinois 60611 United States
  • University of Chicago
  • Chicago Illinois 60637 United States
  • The University of Iowa - Division of Hematology, Oncology and Blood & Marrow Transplantation
  • Iowa City Iowa 52242 United States
  • Norton Cancer Institute
  • Louisville Kentucky 40202 United States
  • Univ of Michigan Medical Center
  • Ann Arbor Michigan 48109 United States
  • Karmanos Cancer Institute - Wayne State University
  • Detroit Michigan 48201 United States
  • Minnesota Oncology
  • Minneapolis Minnesota 55404 United States
  • Nebraska Cancer Specialists
  • Omaha Nebraska 68130 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89169 United States
  • Rutgers Cancer Institute of New Jersey
  • New Brunswick New Jersey 08903 United States
  • Weill Medical College of Cornell University
  • New York New York 10021 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States
  • Levine Cancer Institute
  • Charlotte North Carolina 28204 United States
  • Hematology Oncology Associates, PC
  • Medford Oregon 97504 United States
  • Northwest Cancer Specialists PC
  • Tualatin Oregon 97062 United States
  • Penn State Milton S. Hershey Medical Ctr.
  • Hershey Pennsylvania 17033 United States
  • University of Pittsburgh Medical Center (UPMC)
  • Pittsburgh Pennsylvania 15232 United States
  • Carolina Urologic Research Center
  • Myrtle Beach South Carolina 29572 United States
  • SCRI - Sarah Cannon Research Institute
  • Nashville Tennessee 37203 United States
  • Texas Oncology-Dallas Presbyterian Hospital
  • Dallas Texas 75231 United States
  • Texas Oncology - Sammons Cancer Center
  • Dallas Texas 75246 United States
  • UT Southwestern Medical Center
  • Dallas Texas 75390 United States
  • Texas Oncology-Denton South
  • Denton Texas 76210 United States
  • Texas Oncology-Memorial City
  • Houston Texas 77024 United States
  • University of Texas MD Anderson Cancer Center
  • Houston Texas 77030 United States
  • Virginia Oncology Associates
  • Hampton Virginia 23666 United States
  • University of Wisconsin School of Medicine and Public Health
  • Madison Wisconsin 53792 United States
  • LKH-Univ. Klinikum Graz
  • Graz A-8036 Austria
  • Krankenhaus der Barmherzigen Schwestern Linz
  • Linz 4020 Austria
  • Krankenhaus der Barmherzigen Brüder
  • Vienna 1020 Austria
  • Medical University Vienna
  • Vienna A-1090 Austria
  • O.L.V. Ziekenhuis
  • Aalst 9300 Belgium
  • Cliniques Universitaires Saint Luc
  • Brussel 1200 Belgium
  • Clinique Notre Dame
  • Charleroi 6000 Belgium
  • U.Z. Gent
  • Gent 9000 Belgium
  • GZA Ziekenhuizen- Campus St Augustinus
  • Wilrijk 2610 Belgium
  • ICO, Site Paul Papin
  • Angers Cedex 49055 France
  • Institut Bergonié
  • Bordeaux France
  • Centre Francois Baclesse
  • Caen Cédex 05 14076 France
  • Centre Georges-François Leclerc
  • Dijon 21000 France
  • Centre Leon Bérard
  • Lyon 69008 France
  • Centre Antoine Lacassagne
  • Nice Cedex 2 06189 France
  • Institut de Cancérologie du Gard
  • Nîmes 30029 France
  • Hospital Saint-Louis
  • Paris Cedex 10 75475 France
  • Hopital Europeen Georges-Pompidou
  • Paris Cedex 15 75908 France
  • I.C.O. René Gauducheau
  • Saint Herblain Cedex 44805 France
  • Hopital Foch
  • Suresnes 92150 France
  • Institut Universitaire du Cancer Toulouse - Oncopole
  • Toulouse Cedex 09 31059 France
  • Gustave Roussy
  • Villejuif Cedex 94805 France
  • Vivantes Klinikum Am Urban, Abt. fur Kardiologie
  • Berlin 10967 Germany
  • Waldkrankenhaus St. Marien -Urologische Universitätsklinik-
  • Erlangen 91054 Germany
  • Kliniken Essen-Mitte; Evangelische Huyssens-Stiftung
  • Essen 45136 Germany
  • Goethe Universität Frankfurt
  • Frankfurt 60590 Germany
  • Universitatsklinikum Freiburg
  • Freiburg 79106 Germany
  • Universitätsmedizin Greifswald
  • Greifswald 17475 Germany
  • Georg-August-Universitaet Goettingen - Innere Medizin - Haematologie, Onkologie
  • Göttingen 37075 Germany
  • Asklepios Klinik Altona
  • Hamburg 22763 Germany
  • Medizinische Hochschule Hannover;Klinik f. Urologie u. Urologische Onkologie
  • Hannover 30625 Germany
  • University Hospital Heidelberg
  • Heidelberg 69120 Germany
  • Klinikum rechts der Isar der TU Muenchen
  • Muenchen 81675 Germany
  • University hospital Muenster, Dpt. of Urology
  • Muenster 48129 Germany
  • Caritas Krankenhaus St. Josef - Innere Medizin II
  • Regensburg 93053 Germany
  • Klinikum St. Elisabeth
  • Straubing 94315 Germany
  • Kliniken Nordoberpfalz, Klinik für Urologie
  • Weiden/Opf 92637 Germany
  • Soroka Medical Center
  • Beer Sheba 84101 Israel
  • Asaf Harofe Medical Center
  • Beer Yaakov 60930 Israel
  • Rambam Medical Center
  • Haifa 31096 Israel
  • Meir Medical Center
  • Kfar-Saba 44281 Israel
  • Rabin Medical Center - Bellins
  • Petah Tikva 49100 Israel
  • Sourasky Medical Center, Tel Aviv Sourasky Med Ctr
  • Tel-Aviv 64239 Israel
  • Unità Operativa di Oncologia Medica
  • Arezzo 52100 Italy
  • Oncologia-IRCCS IRST
  • Meldola 47014 Italy
  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano 20100 Italy
  • Oncologia Medica A - Ist Naz Tumori G Pascale
  • Napoli 80131 Italy
  • Ospedale Maggiore della Carità
  • Novara 28100 Italy
  • Oncologia Medica Azienda Sanitaria Ospedaliera San Luigi Gonzaga
  • Orbassano 10043 Italy
  • Istituto Oncologico Veneto - IRCCS
  • Padova 35128 Italy
  • Oncologia Medica - Azienda Ospedaliero Universitaria Di Parma
  • Parma 43126 Italy
  • Azienda Ospedaliero Universitaria Pisana
  • Pisa 56126 Italy
  • Azienda Ospedaliera San Camillo - Roma
  • Roma 00152 Italy
  • UOC di Oncologia Medica Università Cattolica del Sacro Cuore Policlinico Universitario A. Gemelli
  • Roma 00168 Italy
  • University Hospital Umberto I
  • Rome 00161 Italy
  • Istituto Clinico Humanitas UO di Emodinamica e Cradiologia Interventistica
  • Rozzano 20089 Italy
  • Oncologia Medica-Città Della Salute E Della Scienza Di Torino
  • Torino 10126 Italy
  • Azienda Ospedaliero - Universitaria Ospedali Riuniti
  • Torrette Di Ancona 60126 Italy
  • Chungnam National University Hospital - Dept. of Internal Medicine
  • Daejeon 301-721 Korea, Republic of
  • National Cancer Center
  • Goyangsi 410-769 Korea, Republic of
  • Gachon University Gil Medical Center
  • Incheon 21565 Korea, Republic of
  • Severance Hospital
  • Seoul 03722 Korea, Republic of
  • Asan Medical Center (AMC)
  • Seoul 05505 Korea, Republic of
  • Samsung Medical Center
  • Seoul 135-710 Korea, Republic of
  • Arensia Exploratory Medicine
  • Chisinau MD 2025 Moldova, Republic of
  • Spitalul Clinic de Urologie Prof. Dr. Theodor Burghele
  • Bucharest 050659 Romania
  • Spitalul Clinic de Urologie Prof. Dr. Theodor Burghele
  • Bucharest 050659 Romania
  • Spitalul Clinic Sf. Maria
  • Bucharest 11172 Romania
  • Institutul Clinic Fundeni
  • Bucuresti 022328 Romania
  • Arensia Exploratory Medicine - Romania
  • Bucuresti 050159 Romania
  • Institutul Oncologic "Prof Dr. Ion Chiricuta" Cluj-Napoca
  • Cluj-Napoca 400015 Romania
  • ONCOLAB
  • Craiova 200385 Romania
  • Institutul Regional de Oncologie Iasi
  • Iasi 700483 Romania
  • Spitalul Clinic Municipal De Urgenta Timisoara; Sectia Oncologie
  • Timisoara Romania
  • Altai Regional Oncology Dispensary
  • Barnaul 656049 Russian Federation
  • Cancer Research Center
  • Moscow N/A 115478 Russian Federation
  • Scientific Research Institute of Urology
  • Moscow 105425 Russian Federation
  • Hertzen Oncology Research Institute
  • Moscow 125284 Russian Federation
  • Clinical Oncology Dispensary
  • Omsk 644013 Russian Federation
  • Pyatigorsk Regional Oncology Dispensary
  • Pyatigorsk 357502 Russian Federation
  • Leningradski Regional Oncological Dispensary
  • Saint-Petersburg 191104 Russian Federation
  • Russian Scientific Center of Radiology and Surgical Technologies
  • Saint-Petersburg 197758 Russian Federation
  • Bashkiria State Medical University
  • Ufa 450000 Russian Federation
  • Hospital Universitari Germans Trias i Pujol
  • Badalona Spain
  • Hospital Universitario Vall d´Hebron
  • Barcelona 08035 Spain
  • Hospital Clinic de Barcelona
  • Barcelona 08036 Spain
  • Hospital U. Gregorio Marañón
  • Madrid 28007 Spain
  • Fundacion Jimenez Diaz
  • Madrid 28020 Spain
  • Hospital Universitario La Paz
  • Madrid 28046 Spain
  • Centro Integral Oncológico Clara Campal
  • Madrid 28050 Spain
  • Hosp. Virgen de La Victoria
  • Málaga 29010 Spain
  • Clinica Universitaria de Navarra
  • Pamplona 31008 Spain
  • Hospital Virgen del Rocío
  • Sevilla 41013 Spain
  • Taichung Veterans General Hospital
  • Taichung 40705 Taiwan
  • National Cheng Kung University Hospital
  • Tainan 70403 Taiwan
  • National Taiwan University Hospital
  • Taipei 10002 Taiwan
  • Chang Gung Memorial Hospital- Linkou
  • Taoyuan 333 Taiwan
  • Royal Blackburn Hospital
  • Blackburn BB2 3HH United Kingdom
  • Ninewells Hospital
  • Dundee DD1 9SY United Kingdom
  • Queens Hospital
  • Essex RM7 0AG United Kingdom
  • Charing Cross Hospital
  • London W6 8RF United Kingdom
  • Derriford Hospital
  • Plymouth PL6 8DH United Kingdom
  • Royal Marsden Hospital
  • Sutton SM2 5PT United Kingdom
  • Clatterbridge Centre for Oncology
  • Wirral CH63 4JY United Kingdom

View trial on ClinicalTrials.gov