Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations
- Conditions
- Upper Tract Urothelial CarcinomasUrothelial Bladder Cancer
- Interventions
- Drug: Placebo
- Registration Number
- NCT04197986
- Lead Sponsor
- QED Therapeutics, Inc.
- Brief Summary
This is a Phase 3 multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy of infigratinib (an oral targeted FGFR1-3 inhibitor) versus placebo, as adjuvant treatment following surgery in adult subjects with invasive urothelial carcinoma and susceptible FGFR3 genetic alterations (mutations, and gene fusions or rearrangements) who have disease that is considered at high risk for recurrence with surgery alone. The study enrolls subjects with either bladder cancer post radical cystectomy or upper tract urothelial cancer post distal ureterectomy and/or nephrectomy. Study treatment is randomized 1:1 between infigratinib or placebo with treatment up to 1 year or until invasive local, distal, or metastatic disease recurrence confirmed by independent imaging reviewer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 39
Not provided
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Presence of positive invasive surgical margins following nephroureterectomy, distal ureterectomy, or cystectomy. In subjects not eligible for further surgery, radiotherapy, or other efficacious treatment, microscopic positive noninvasive margins (eg, carcinoma in situ) without gross residual disease are allowed.
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Have received Bacillus Calmette-Guerin (BCG) or other intravesical therapy for Non-Muscle Invasive Bladder Cancer (NMIBC) within the previous 30 days.
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Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known moderate or strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Prior anticancer or other therapies are restricted as follows:
- Prior adjuvant treatment for urothelial cancer is not allowed.
- Prior neoadjuvant therapy (eg, chemotherapy, immunotherapy, or investigational) is allowed if inclusion criterion #4 is met. Prior neoadjuvant chemotherapy must have been completed within a period of time that is greater than the cycle length used for that treatment before first dose of study drug.
- Prior biologic, immunotherapy, or investigational therapy should have been completed within a period that is ≥5 half-lives or 30 days, whichever is shorter, before the first dose of study drug.
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Have previously or currently is receiving treatment with a mitogen-activated protein kinase (MEK) or selective FGFR inhibitor.
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Have a history of primary malignancy within the past 3 years other than (1) invasive UBC or UTUC (ie, disease under study), (2) noninvasive urothelial carcinoma, (3) any adequately treated in situ carcinoma or non-melanoma carcinoma of the skin, (4) any other curatively treated malignancy that is not expected to require treatment for recurrence during participation in the study, or (5) an untreated cancer on active surveillance that may not affect the subject's survival status for ≥3 years based on clinician assessment/statement and with medical monitor approval.
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Have current evidence of corneal keratopathy or retinal disorder confirmed by ophthalmic examination. Subjects with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
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Have a history and/or current evidence of extensive tissue calcification
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Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib
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Have current evidence of endocrine alterations of calcium/phosphate homeostasis (eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis), unless well controlled.
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Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, or Seville oranges or products containing juice of these fruits within 7 days before the first dose of study drug; have taken any Chinese herbal medicine or Chinese patent medicine treatments with anticancer activity within 14 days of the first dose of study drug.
-
Have insufficient bone marrow function:
- Absolute neutrophil count (ANC) <1,000/mm3 (1.0 × 109/L).
- Platelets <75,000/mm3 (<75 × 109/L).
- Hemoglobin <8.5 g/dL; transfusion support is allowed if >1 week before randomization and hemoglobin remains stable.
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Have insufficient hepatic and renal function:
- Total bilirubin >1.5 × upper limit of normal (ULN) of the testing laboratory (for subjects with documented Gilbert syndrome, direct bilirubin must be ≤1.5 × ULN and enrollment requires approval by the medical monitor).
- AST/SGOT and ALT/SGPT >2.5 × ULN of the testing laboratory.
- Serum creatinine >1.5 × ULN or a calculated or measured creatinine clearance of <30 mL/min.
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Have amylase or lipase >2.0 × ULN.
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Have abnormal calcium or phosphorus:
- Inorganic phosphorus higher than 1.02 × ULN of the testing laboratory.
- Total serum calcium (can be corrected) higher than 1.02 × ULN of the testing laboratory.
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Have clinically significant cardiac disease including any of the following:
- New York Heart Association (NYHA) Class ≥2B; subjects with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the NYHA classification.
- Uncontrolled hypertension
- Presence of CTCAE v5.0 Grade ≥2 ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction abnormality.
- Unstable angina pectoris or acute myocardial infarction ≤3 months before the first dose of study drug.
- Average QTcF >470 msec (males and females). Note: If the QTcF is >470 msec in the first ECG, a total of 3 ECGs separated by ≥5 minutes should be performed. If the average of these 3 consecutive results for QTcF is ≤470 msec, the subject meets eligibility in this regard.
- History of congenital long QT syndrome.
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Have had a recent (≤3 months before the first dose of study drug) transient ischemic attack or stroke.
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If female, are pregnant or nursing (lactating).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Infigratinib 125 mg Infigratinib Participants will be randomly assigned (1:1) to receive oral infigratinib administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks Placebo Placebo Participants will be randomly assigned (1:1) to receive oral placebo administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks
- Primary Outcome Measures
Name Time Method Centrally Determined Disease-free Survival (DFS) The number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause. DFS was defined as the number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause (referred as DFS event), whichever occurs earlier.
Due to early termination of the study by the sponsor, results will focus primarily on the primary and key secondary endpoints of the study. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.
- Secondary Outcome Measures
Name Time Method Metastasis-free Survival (MFS) The time from randomization to any metastatic recurrence as determined by the investigator, or death due to any cause. MFS was defined as the time from randomization to any metastatic recurrence as determined by the investigator, or death due to any cause, whichever occurred earlier. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.
Overall Survival (OS) The number of months from randomization to death. Overall survival time was defined as the number of months from randomization to death. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.
Investigator-reviewed DFS Including Intraluminal Low-Risk Recurrence The number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause. Investigator assessment of intraluminal low-risk recurrence as assessed by DFS. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.
Number of Participants With Adverse Events (AEs) From first dose to last dose of study treatment +30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm). Number of participants with AEs
Number of Participants With Serious Adverse Events (SAEs) From first dose to last dose of study treatment +30 days (an average of 4 months for the infigratinib arm and 8 months for the placebo arm) Number of Participants with SAEs
Investigator-assessed DFS The number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause. DFS was defined as the number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause (referred as DFS event), whichever occurs earlier. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.
Trial Locations
- Locations (136)
The Ohio State University College of Medicine
🇺🇸Columbus, Ohio, United States
Associated Medical Professionals - Syracuse
🇺🇸Syracuse, New York, United States
New Jersey Urology - Saddle Brook
🇺🇸Saddle Brook, New Jersey, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
The University of Toledo Medical Center
🇺🇸Toledo, Ohio, United States
New Jersey Urology
🇺🇸Voorhees, New Jersey, United States
UT Southwestern
🇺🇸Richardson, Texas, United States
Albany Medical Center - Division of Urology
🇺🇸Albany, New York, United States
Harold C. Simmons Comprehensive Cancer Center
🇺🇸Dallas, Texas, United States
CHU de Liège - Sart Tilman
🇧🇪Liège, Liège/Belgium, Belgium
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Madrid/Spain, Spain
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹Meldola, Italy
Istituto Europeo di Oncologia
🇮🇹Milan, Italy
Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
🇮🇹Napoli, Naples, Italy
Universitatsklinikum des Saarlandes Klinik fur Urologie & Kinderurologie
🇩🇪Homburg/saar, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
VHIO
🇪🇸Barcelona, Barcelona/Spain, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Madrid/Spain, Spain
Ospedale di Trento - Presidio Ospedaliero Santa Chiara
🇮🇹Trento, Italy
Sofia
🇪🇸Barcelona, Barcelona/Spain, Spain
Universitätsklinikum des Saarlandes Klinik für Urologie & Kinderurologie
🇩🇪Homburg, Germany
Caritas-Krankenhaus St. Josef Klinik für Urologie
🇩🇪Regensburg, Germany
Azienda Ospedaliero-Universitaria Pisana
🇮🇹Pisa, Italy
Urologie
🇩🇪Berlin, Germany
Ospedale di Cremona
🇮🇹Cremona, Cremona/Italy, Italy
IRCCS Centro di Riferimento Oncologico di Basilicata
🇮🇹Volterra, Italy
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Reggio Emilia/Italy, Italy
Institut Català d'Oncologia Badalona
🇪🇸Badalona, Barcelona, Spain
Charite Universitaetsmedizin Berlin
🇩🇪Berlin, Germany
Marien Hospital Herne - Universitätsklinikum der Ruhr-Universität Bochum
🇩🇪Herne, Nordrhein-Westfalen, Germany
University Hospital Duesseldorf
🇩🇪Duesseldorf, Germany
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
🇪🇸Barcelona, Barcelona/Spain, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Madrid/Spain, Spain
Ospedale Policlinico San Martino
🇮🇹Genova, Genova/Italy, Italy
IRCCS di Reggio Emilia
🇮🇹Reggio Emilia, Italy
Hospital Clinico San Carlos
🇪🇸Madrid, Madrid/Spain, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Sevilla/Spain, Spain
Universitatsklinikum Magdeburg
🇩🇪Magdeburg, Germany
Hospital del Mar
🇪🇸Barcelona, Spain
The Netherlands Cancer Institute
🇳🇱Amsterdam, Netherlands
Citta Della Salute e Della Scienz - Torino
🇮🇹Torino, Italy
Lister Hospital
🇬🇧Stevenage, United Kingdom
Hospital Universitario Reina Sofía
🇪🇸Córdoba, Córdoba/Spain, Spain
Institut Català d'Oncologia Girona
🇪🇸Girona, Girona/Spain, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Madrid/Spain, Spain
MD Anderson Cancer Center Madrid
🇪🇸Madrid, Madrid/Spain, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Virgen De La Salud
🇪🇸Toledo, Toledo/Spain, Spain
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
UChicago Medicine Duchossois Center for Advanced Medicine (DCAM) - Hyde Park
🇺🇸Chicago, Illinois, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Bayor College of Medicine
🇺🇸Houston, Texas, United States
Houston Methodist Hospital- Department of Urology
🇺🇸Houston, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Zuyderland MC locatie Sittard
🇳🇱Geleen, Netherlands
ZNA Middelheim
🇧🇪Antwerpen, Belgium
Universitair Ziekenhuis Leuven
🇧🇪Leuven, Belgium
Canisius-Wilhelmina Ziekenhuis
🇳🇱Nijmegen, Gelderland, Netherlands
Bioclinic Thessalonikis
🇬🇷Thessaloníki, Makedonia, Greece
University Multiprofile Hospital For Active Treatment Deva Maria
🇧🇬Burgas, Bulgaria
Multiprofile Hospital For Active Treatment "Sveta Sofia"
🇧🇬Sofia, Bulgaria
Henry Dunant Hospital Center
🇬🇷Athens, Attica, Greece
Anassa General Clinic
🇬🇷Volos, Greece
Università Campus Bio-Medico di Roma
🇮🇹Roma, Roma/Italy, Italy
Azienda Ospedaliero - Universitaria San Luigi Gonzaga
🇮🇹Orbassano, Torino, Italy
Azienda Universitaria Ospedaliera Consorziale - Policlinico di Bari
🇮🇹Bari, Italy
A.O.U.C. Polclinico di Bari U.O. Oncologia Medica Universitaria
🇮🇹Bari, Italy
ASST Cremona
🇮🇹Casalmaggiore, Italy
Ospedale Policlinico San Martino Irccs
🇮🇹Genova, Italy
Fondazione IRCCS INT Milano
🇮🇹Milan, Italy
Policlinico Universitario Campus Biomedico
🇮🇹Roma, Italy
Int Pascale Napoli
🇮🇹Napoli, Italy
AOU San Luigi Gonzaga
🇮🇹Orbassano, Italy
Hôpital Européen Georges-Pompidou
🇫🇷Paris, Ile-de-France, France
Centre de Lutte Contre le Cancer - Centre Léon Bérard
🇫🇷Lyon, Rhone-Alpes, France
The Urology Center of Colorado
🇺🇸Denver, Colorado, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Duke University Cancer Center
🇺🇸Durham, North Carolina, United States
Oncology Hematology Care
🇺🇸Cincinnati, Ohio, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Huntsman Cancer Institute and Hospital
🇺🇸Salt Lake City, Utah, United States
Urology Associates
🇺🇸Nashville, Tennessee, United States
Urology San Antonio
🇺🇸San Antonio, Texas, United States
Hopital Bichat - Claude - Bernard
🇫🇷Paris, France
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Arizona Oncology Associates
🇺🇸Tucson, Arizona, United States
Urological Research Network CORP
🇺🇸Hialeah, Florida, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
Universitätsklinikum Düsseldorf
🇩🇪Duesseldorf, Nordrhein-Westfalen, Germany
City of Hope
🇺🇸Duarte, California, United States
City of Hope - Duarte
🇺🇸Duarte, California, United States
Loma Linda University Faculty Medical Clinics
🇺🇸Loma Linda, California, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
DuPage Medical Group - Warrenville Road
🇺🇸Lisle, Illinois, United States
Lakeland Regional Health Hollis Cancer Center
🇺🇸Lakeland, Florida, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Saint Louis University- SLUCare Academic Pavilion
🇺🇸Saint Louis, Missouri, United States
Accellacare-DuPage Medical Group
🇺🇸Raleigh, North Carolina, United States
University of Toledo
🇺🇸Arlington, Ohio, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Cliniques Universitaires Saint-Luc
🇧🇪Brussel, Belgium
University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD
🇧🇬Pleven, Bulgaria
BC Cancer- Vancouver
🇨🇦Vancouver, British Columbia, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
McGill University Health Centre (MUHC)
🇨🇦Montréal, Quebec, Canada
CHU de Québec Université Laval
🇨🇦Québec, Canada
Hôpital Universitaire Pitié Salpêtrière
🇫🇷Paris, Ile-de-France, France
BC Cancer - Vancouver
🇨🇦Vancouver, Canada
CHU de Nantes Hopital Hotel Dieu
🇫🇷Nantes, France
Institut de Cancerologie Strasbourg Europe
🇫🇷Strasbourg, Strasbourg/France, France
Institut Claudius Regaud
🇫🇷Toulouse, Toulouse/France, France
Hôpital Morvan
🇫🇷Brest, France
Gustave Roussy
🇫🇷Villejuif, France
Centre Eugène Marquis
🇫🇷Rennes, France
Institut De Cancerologie De L'ouest - Site Saint-Herblain
🇫🇷Saint-Herblain, France
Centre Hospitalier Privé Saint-Grégoire
🇫🇷Saint-Grégoire, France
Charité - Universitatsmedizin Berlin
🇩🇪Berlin, Berlin/Germany, Germany
Clinique Mutualiste de l'Estuaire
🇫🇷Saint-Nazaire, France
Urologicum Duisburg
🇩🇪Duisburg, Nordrhein-WestFalen, Germany
Universitätsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Centro di Riferimento Oncologico
🇮🇹Aviano, Italy
Hospital Universitario Puerta Hierro-Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Fundacion Instituto Valenciano de Oncologia
🇪🇸Valencia, València, Spain
Althaia Xarxa Assistencial Universitària de Manresa
🇪🇸Manresa, Spain
Tulane University/Southeastern Louisiana VA Health Care
🇺🇸New Orleans, Louisiana, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Hospital Parc Taulí de Sabadell
🇪🇸Sabadell, Barcelona, Spain
Guy's and St Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom