Bladder Cancer Clinical Trial

Study of Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations

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.

View Eligibility Criteria

Eligibility Criteria

Key Inclusion Criteria

Are randomized within 120 days following nephroureterectomy, distal ureterectomy or cystectomy.

Have histologically or cytologically confirmed, invasive urothelial carcinoma with susceptible FGFR3 alterations. Variant histology is allowed provided urothelial carcinoma is predominant (>50%). Neuroendocrine (including small and large cell), sarcomatoid, and plasmacytoid variants are excluded (any component).

Regarding samples and documentation of FGFR3

i. FGFR3 mutation is confirmed if: FGFR3 gene is mutated in Exon 7 (R248C, S249C), Exon 10 (G370C, A391E, Y373C), or Exon 15 (K650M/T, K650E/Q)

OR

ii. FGFR3 gene fusion or FGFR3 rearrangement is confirmed based on the following genomic criteria if:

Any fusion/rearrangement with a literature-derived known partner gene regardless of strand or frame.
Fusion/rearrangements in the same strand that are in frame with a novel partner gene.
Fusion/rearrangements with one breakpoint in the intron 17 - exon 18 hotspot region and the other breakpoint in an intergenic region or another gene. This rule excludes 3' duplications comprising only exon 18.
iii. The amino acid numbers for the FGFR3 mutations refer to the functional FGFR3 isoform 1 (NP_000133.1) that is the NCBI Refseq ID used to report genetic alterations in FGFR3 by the FoundationOne® CDx test (F1CDx, Foundation Medicine, USA).

iv. FGFR3 alteration must be confirmed by Foundation Medicine for F1CDx testing:

The tumor sample to be used should be from the definitive surgical resection (cystectomy, nephroureterectomy, or distal ureterectomy), or from an archival biopsy of confirmed invasive urothelial carcinoma (≥pT2).
If status post neoadjuvant chemotherapy, pathologic stage at surgical resection must be Stage ≥ ypT2 and/or yN+. Prior neoadjuvant therapy is defined as at least 3 cycles of neoadjuvant cisplatin-based chemotherapy with a planned cisplatin dose of 70 mg/m2/cycle. Subjects who received less than this or non-cisplatin-based neoadjuvant treatment are not excluded.
If not status post neoadjuvant chemotherapy, is ineligible to receive cisplatin-based adjuvant chemotherapy based on Galsky criteria:
Subjects who refuse cisplatin-based chemotherapy or who are ineligible to receive cisplatin-based chemotherapy based on Galsky criteria must also meet the following criteria:
Must have a centrally reviewed negative postoperative computed tomography (CT) (defined as lymph nodes with short axis <1.0 cm and without growth and no distant metastases according to [RECIST v1.1 criteria or negative biopsy within 28 days before randomization to confirm absence of disease at baseline.
Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
If a woman of childbearing potential, must have a negative pregnancy test within 7 days of the first dose of study drug. Sexually active males must use a condom during intercourse while taking study drug and for 1 month after the last dose of study drug and should not father a child during this period

Key Exclusion Criteria:

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.
Have received Bacillus Calmette-Guerin (BCG) or other intravesical therapy for Non-Muscle Invasive Bladder Cancer (NMIBC) within the previous 30 days.

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.
Have previously or currently is receiving treatment with a mitogen-activated protein kinase (MEK) or selective FGFR inhibitor.
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.
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.
Have a history and/or current evidence of extensive tissue calcification
Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib
Have current evidence of endocrine alterations of calcium/phosphate homeostasis (eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis), unless well controlled.
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 × 109L).
Hemoglobin <8.5 g/dL; transfusion support is allowed if >1 week before randomization and hemoglobin remains stable.

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 mLmin.
Have amylase or lipase >2.0 × ULN.

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.

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.
Have had a recent (≤3 months before the first dose of study drug) transient ischemic attack or stroke.
If female, are pregnant or nursing (lactating).

Study is for people with:

Bladder Cancer

Phase:

Phase 3

Estimated Enrollment:

218

Study ID:

NCT04197986

Recruitment Status:

Active, not recruiting

Sponsor:

QED Therapeutics, Inc.

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There are 100 Locations for this study

See Locations Near You

Arizona Oncology Associates
Tucson Arizona, 85711, United States
City of Hope - Duarte
Duarte California, 91010, United States
City of Hope
Duarte California, 91010, United States
Loma Linda University Faculty Medical Clinics
Loma Linda California, 92350, United States
USC Norris Comprehensive Cancer Center
Los Angeles California, 90033, United States
University of Colorado Cancer Center
Aurora Colorado, 80045, United States
The Urology Center of Colorado
Denver Colorado, 80211, United States
Georgetown University Medical Center
Washington District of Columbia, 20007, United States
Urological Research Network CORP
Hialeah Florida, 33016, United States
Mayo Clinic - Jacksonville
Jacksonville Florida, 32224, United States
Lakeland Regional Health Hollis Cancer Center
Lakeland Florida, 33805, United States
Emory University
Atlanta Georgia, 30322, United States
Winship Cancer Institute of Emory University
Atlanta Georgia, 30322, United States
Northwestern University Feinberg School of Medicine
Chicago Illinois, 60611, United States
UChicago Medicine Duchossois Center for Advanced Medicine (DCAM) - Hyde Park
Chicago Illinois, 60637, United States
DuPage Medical Group - Warrenville Road
Lisle Illinois, 60532, United States
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis Indiana, 46202, United States
Tulane University/Southeastern Louisiana VA Health Care
New Orleans Louisiana, 70112, United States
Johns Hopkins Hospital
Baltimore Maryland, 21287, United States
Saint Louis University- SLUCare Academic Pavilion
Saint Louis Missouri, 63110, United States
University of Nebraska Medical Center
Omaha Nebraska, 68198, United States
Dartmouth-Hitchcock Medical Center
Lebanon New Hampshire, 03766, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack New Jersey, 07601, United States
New Jersey Urology - Saddle Brook
Saddle Brook New Jersey, 07663, United States
New Jersey Urology
Voorhees New Jersey, 08043, United States
Albany Medical Center - Division of Urology
Albany New York, 12208, United States
Associated Medical Professionals - Syracuse
Syracuse New York, 13210, United States
Duke University Cancer Center
Durham North Carolina, 27710, United States
Accellacare-DuPage Medical Group
Raleigh North Carolina, 27609, United States
Wake Forest Baptist Health
Winston-Salem North Carolina, 27157, United States
University of Toledo
Arlington Ohio, 43606, United States
Oncology Hematology Care
Cincinnati Ohio, 45242, United States
Cleveland Clinic
Cleveland Ohio, 44195, United States
The Ohio State University College of Medicine
Columbus Ohio, 43210, United States
The University of Toledo Medical Center
Toledo Ohio, 43614, United States
Stephenson Cancer Center
Oklahoma City Oklahoma, 73104, United States
Medical University of South Carolina
Charleston South Carolina, 29425, United States
Urology Associates
Nashville Tennessee, 37209, United States
Harold C. Simmons Comprehensive Cancer Center
Dallas Texas, 75390, United States
Bayor College of Medicine
Houston Texas, 77030, United States
Houston Methodist Hospital- Department of Urology
Houston Texas, 77030, United States
The University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States
UT Southwestern
Richardson Texas, 75080, United States
Urology San Antonio
San Antonio Texas, 78229, United States
Huntsman Cancer Institute and Hospital
Salt Lake City Utah, 84112, United States
Seattle Cancer Care Alliance
Seattle Washington, 98109, United States
West Virginia University
Morgantown West Virginia, 26506, United States
CHU de Liège - Sart Tilman
Liège Liège/Belgium, 4000, Belgium
ZNA Middelheim
Antwerpen , , Belgium
Cliniques Universitaires Saint-Luc
Brussel , 1200, Belgium
Universitair Ziekenhuis Leuven
Leuven , , Belgium
University Multiprofile Hospital For Active Treatment Deva Maria
Burgas , 8001, Bulgaria
University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD
Pleven , , Bulgaria
Multiprofile Hospital For Active Treatment "Sveta Sofia"
Sofia , , Bulgaria
Cross Cancer Institute
Edmonton Alberta, T6G 1, Canada
BC Cancer- Vancouver
Vancouver British Columbia, V5Z 4, Canada
Princess Margaret Cancer Centre
Toronto Ontario, M5G2M, Canada
McGill University Health Centre (MUHC)
Montréal Quebec, H4A 3, Canada
CHU de Québec Université Laval
Québec , G1R 2, Canada
BC Cancer - Vancouver
Vancouver , , Canada
Hôpital Universitaire Pitié Salpêtrière
Paris Ile-de-France, 75013, France
Hôpital Européen Georges-Pompidou
Paris Ile-de-France, 75015, France
CHU de Nantes Hopital Hotel Dieu
Paris Paris/France, 75018, France
Centre de Lutte Contre le Cancer - Centre Léon Bérard
Lyon Rhone-Alpes, 69008, France
Institut de Cancerologie Strasbourg Europe
Strasbourg Strasbourg/France, 67200, France
Institut Claudius Regaud
Toulouse Toulouse/France, 31059, France
Gustave Roussy
Villejuif Villejuif/France, 94805, France
Hôpital Morvan
Brest , 29200, France
CHU de Nantes Hopital Hotel Dieu
Nantes , , France
Hopital Bichat - Claude - Bernard
Paris , , France
Centre Eugène Marquis
Rennes , 35042, France
Centre Hospitalier Privé Saint-Grégoire
Saint-Grégoire , 35760, France
Institut De Cancerologie De L'ouest - Site Saint-Herblain
Saint-Herblain , , France
Clinique Mutualiste de l'Estuaire
Saint-Nazaire , 44600, France
Gustave Roussy
Villejuif , , France
Charité - Universitatsmedizin Berlin
Berlin Berlin/Germany, 10117, Germany
Universitätsklinikum Düsseldorf
Duesseldorf Nordrhein-Westfalen, 40225, Germany
Urologicum Duisburg
Duisburg Nordrhein-WestFalen, 47179, Germany
Universitätsklinikum Essen
Essen Nordrhein-Westfalen, 45147, Germany
Marien Hospital Herne - Universitätsklinikum der Ruhr-Universität Bochum
Herne Nordrhein-Westfalen, 44625, Germany
Charite Universitaetsmedizin Berlin
Berlin , , Germany
Urologie
Berlin , , Germany
University Hospital Duesseldorf
Duesseldorf , , Germany
Universitatsklinikum des Saarlandes Klinik fur Urologie & Kinderurologie
Homburg/saar , , Germany
Universitätsklinikum des Saarlandes Klinik für Urologie & Kinderurologie
Homburg , , Germany
Universitatsklinikum Magdeburg
Magdeburg , , Germany
Caritas-Krankenhaus St. Josef Klinik für Urologie
Regensburg , 93053, Germany
Universitätsklinikum Tübingen
Tübingen , , Germany
Henry Dunant Hospital Center
Athens Attica, 11526, Greece
Bioclinic Thessalonikis
Thessaloníki Makedonia, 54622, Greece
Anassa General Clinic
Volos , , Greece
Ospedale di Cremona
Cremona Cremona/Italy, 26100, Italy
Ospedale Policlinico San Martino
Genova Genova/Italy, 16132, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola Meldola/Italy, 47014, Italy
Istituto Europeo di Oncologia
Milano Milano/Italy, 20141, Italy
Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
Napoli Naples, 80131, Italy
Azienda Ospedaliero-Universitaria Pisana
Pisa Pisa/italy, 56126, Italy
IRCCS Centro di Riferimento Oncologico di Basilicata
Rionero In Vulture Potenza, 85028, Italy
Arcispedale Santa Maria Nuova
Reggio Emilia Reggio Emilia/Italy, 42100, Italy
Università Campus Bio-Medico di Roma
Roma Roma/Italy, 00128, Italy
Azienda Ospedaliero - Universitaria San Luigi Gonzaga
Orbassano Torino, 10043, Italy
Ospedale di Trento - Presidio Ospedaliero Santa Chiara
Trento Trentino, 38100, Italy
Centro di Riferimento Oncologico
Aviano , , Italy
Azienda Universitaria Ospedaliera Consorziale - Policlinico di Bari
Bari , 70124, 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
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola , , Italy
Fondazione IRCCS INT Milano
Milan , , Italy
Istituto Europeo di Oncologia
Milan , , Italy
Int Pascale Napoli
Napoli , , Italy
AOU San Luigi Gonzaga
Orbassano , , Italy
Azienda Ospedaliero-Universitaria Pisana
Pisa , , Italy
IRCCS di Reggio Emilia
Reggio Emilia , , Italy
Policlinico Universitario Campus Biomedico
Roma , , Italy
Citta Della Salute e Della Scienz - Torino
Torino , , Italy
Ospedale di Trento - Presidio Ospedaliero Santa Chiara
Trento , , Italy
IRCCS Centro di Riferimento Oncologico di Basilicata
Volterra , , Italy
Canisius-Wilhelmina Ziekenhuis
Nijmegen Gelderland, 6532 , Netherlands
The Netherlands Cancer Institute
Amsterdam , , Netherlands
Zuyderland MC locatie Sittard
Geleen , , Netherlands
VHIO
Barcelona Barcelona/Spain, 08003, Spain
Sofia
Barcelona Barcelona/Spain, 08041, Spain
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
Barcelona Barcelona/Spain, 08908, Spain
Institut Català d'Oncologia Badalona
Badalona Barcelona, 08916, Spain
Hospital Parc Taulí de Sabadell
Sabadell Barcelona, 08208, Spain
Hospital Universitario Reina Sofía
Córdoba Córdoba/Spain, 14004, Spain
Institut Català d'Oncologia Girona
Girona Girona/Spain, 17007, Spain
MD Anderson Cancer Center Madrid
Madrid Madrid/Spain, 28033, Spain
Hospital Universitario Ramon y Cajal
Madrid Madrid/Spain, 28034, Spain
Hospital Clinico San Carlos
Madrid Madrid/Spain, 28040, Spain
Hospital Universitario 12 de Octubre
Madrid Madrid/Spain, 28041, Spain
Hospital Universitario La Paz
Madrid Madrid/Spain, 28046, Spain
Hospital Universitario HM Sanchinarro
Madrid Madrid/Spain, 28050, Spain
Hospital Universitario Puerta Hierro-Majadahonda
Majadahonda Madrid, 28222, Spain
Hospital Universitario Virgen del Rocio
Sevilla Sevilla/Spain, 41013, Spain
Hospital Virgen De La Salud
Toledo Toledo/Spain, 45005, Spain
Fundacion Instituto Valenciano de Oncologia
Valencia València, 46009, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona , , Spain
Hospital del Mar
Barcelona , , Spain
Althaia Xarxa Assistencial Universitària de Manresa
Manresa , , Spain
Guy's and St Thomas' NHS Foundation Trust
London , , United Kingdom
Lister Hospital
Stevenage , , United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Bladder Cancer

Phase:

Phase 3

Estimated Enrollment:

218

Study ID:

NCT04197986

Recruitment Status:

Active, not recruiting

Sponsor:


QED Therapeutics, Inc.

How clear is this clinincal trial information?

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