A Study of Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial Cancer
- Conditions
- Urothelial Carcinoma
- Interventions
- Registration Number
- NCT03473743
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to: (a) characterize the safety and tolerability of and to identify the recommended Phase 2 dose (RP2D) and schedule for erdafitinib in combination with cetrelimab, and for erdafitinib in combination with cetrelimab and platinum (cisplatin and carboplatin) chemotherapy and; (b) to evaluate the safety and clinical activity of erdafitinib alone and in combination with cetrelimab in cisplatin-ineligible participants with metastatic or locally advanced urothelial cancer (UC) with select fibroblast growth factor receptor (FGFR) gene alterations and no prior systemic therapy for metastatic disease.
- Detailed Description
This open-label (all people know identity of intervention) and multicenter (when more than one hospital or medical school team work on a medical research study) study to establish the recommended phase 2 dose (RP2D) for erdafitinib and cetrelimab and/or platinum (cisplatin or carboplatin) chemotherapy, and to evaluate the safety of erdafitinib in combination with cetrelimab and platinum chemotherapy in Phase 1b and to evaluate the safety and efficacy of the RP2D of erdafitinib plus cetrelimab versus erdafitinib in Phase 2 in participants with advanced urothelial cancer with select fibroblast growth factor receptor (FGFR) gene alterations. Participants enrolled in Phase 1b erdafitinib + cetrelimab cohort may have received any number of lines of prior therapy, and participants enrolled in Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort will have had no prior systemic therapy for metastatic disease and participants enrolled in Phase 2 will have had no prior systemic therapy for metastatic disease and will be cis-ineligible. Part 1 (Phase 1b: Dose Escalation) will identify safety and RP2Ds of erdafitinib + cetrelimab and erdafitinib + cetrelimab + platinum (cisplatin or carboplatin) chemotherapy, and Part 2 (Phase 2: Dose Expansion) will evaluate erdafitinib monotherapy and the RP2D regimen of the erdafitinib + cetrelimab combination to further characterize safety and clinical activity. The study will be conducted in 3 phases: screening phase, treatment phase, and follow-up phase. Study evaluations include efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, biomarkers, and safety.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 125
- Histologic demonstration of transitional cell carcinoma of the urothelium. Variant urothelial carcinoma histologies such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
- Metastatic or locally advanced urothelial cancer
- Must have measurable disease by radiological imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
- Prior systemic therapy for metastatic urothelial cancer: (a) For Phase 1b erdafitinib + cetrelimab cohort: Any number of lines of prior therapy; (b) For Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: No prior systemic therapy for metastatic disease; and renal function for participants must have a creatinine clearance (CrCl) greater than (>) 30 milliliter per minute (mL/min) to receive carboplatin and >60 mL/min to receive cisplatin as calculated by Cockcroft Gault and (c) Phase 2: No prior systemic therapy for metastatic disease and cisplatin-ineligible based on: ECOG PS 0-1 and at least one of the following criteria: Renal function defined as creatinine clearance (CrCl) less than (˂) 60 mL/min as calculated by Cockcroft-Gault; Grade 2 or higher peripheral neuropathy per NCI-CTCAE version 5.0; Grade 2 or higher hearing loss per NCI-CTCAE version 5.0 OR ECOG PS 2
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: (a) Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2; (b) Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: ECOG 0-1 for cisplatin and 0-2 for carboplatin (c) Phase 2: ECOG 0-2
- Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to Cycle 1 Day 1. For Phase 1b, participants who have received the following prior antitumor therapy: received nitrosoureas and mitomycin C within 6 weeks
- Phase 1b erdafitinib + cetrelimab cohort: Chemotherapy within 3 weeks of Cycle 1 Day 1; Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort and Phase 2: Prior neoadjuvant/adjuvant chemotherapy is allowed if the last dose was given >12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation
- Prior anti-programmed death receptor-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-programmed death ligand-2 (PD-L2) therapy. Prior neoadjuvant/adjuvant checkpoint inhibitor therapy is allowed if the last dose was given more than (>)12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation. PD-1 for non-muscle invasive bladder cancer is also allowed
- Active malignancies requiring concurrent therapy other than urothelial cancer
- Symptomatic central nervous system metastases
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1b: Dose Escalation Erdafitinib Two dosing cohorts (erdafitinib and cetrelimab; and erdafitinib, cetrelimab and cisplatin/carboplatin) are explored in Phase 1b of the study. Participants will receive erdafitinib orally followed by cetrelimab intravenously (IV) and carboplatin/cisplatin IV as a part of platinum chemotherapy. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified. Phase 2: Dose Expansion Cetrelimab The participants will be randomized in a 1:1 manner to receive either erdafitinib alone (orally) or the identified RP2D of Phase 1b for erdafitinib (orally) in combination with cetrelimab (IV). Phase 1b: Dose Escalation Cisplatin Two dosing cohorts (erdafitinib and cetrelimab; and erdafitinib, cetrelimab and cisplatin/carboplatin) are explored in Phase 1b of the study. Participants will receive erdafitinib orally followed by cetrelimab intravenously (IV) and carboplatin/cisplatin IV as a part of platinum chemotherapy. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified. Phase 2: Dose Expansion Erdafitinib The participants will be randomized in a 1:1 manner to receive either erdafitinib alone (orally) or the identified RP2D of Phase 1b for erdafitinib (orally) in combination with cetrelimab (IV). Phase 1b: Dose Escalation Cetrelimab Two dosing cohorts (erdafitinib and cetrelimab; and erdafitinib, cetrelimab and cisplatin/carboplatin) are explored in Phase 1b of the study. Participants will receive erdafitinib orally followed by cetrelimab intravenously (IV) and carboplatin/cisplatin IV as a part of platinum chemotherapy. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified. Phase 1b: Dose Escalation Carboplatin Two dosing cohorts (erdafitinib and cetrelimab; and erdafitinib, cetrelimab and cisplatin/carboplatin) are explored in Phase 1b of the study. Participants will receive erdafitinib orally followed by cetrelimab intravenously (IV) and carboplatin/cisplatin IV as a part of platinum chemotherapy. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.
- Primary Outcome Measures
Name Time Method Phase 2: Number of Participants With Treatment-emergent Adverse Event (TEAEs) From Day 1 up to 36 months Number of participants with TEAEs were reported. An adverse event is any untoward medical event that occurs in a participant administered an investigational product and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs were defined as adverse events with onset or worsening on or after date of first dose of study treatment.
Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs) Up to 8 weeks Number of participants with DLTs were reported. The DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE version 5.0) are specific adverse events defined as grade 3 (severe), grade 4 (life-threatening), and grade 5 (death) non-hematological toxicity or hematological toxicity.
Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment From Day 1 up to 36 months ORR is defined as the percentage of participants who achieved confirmed complete response (CR) or confirmed partial response (PR), according to response evaluation criteria in solid tumors (RECIST) version1.1. As per RECIST version 1.1, CR: disappearance of all lesions; all lymph nodes were non-pathological in size and normalization of tumor marker level; PR: greater than or equal to (\>=) 30 percent (%) decrease in the sum of the diameters of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of nontarget lesions.
- Secondary Outcome Measures
Name Time Method Phase 1b and Phase 2: Serum Concentration of Cetrelimab Up to 6 years 1 month Phase 2: Number of Participants With Abnormal Laboratory Values Up to 6 years 1 month Phase 2: Progression-free Survival (PFS) Up to 6 years 1 month Phase 1b and Phase 2: Plasma Concentration of Erdafitinib Up to 6 years 1 month Phase 2: Number of Participants With Serious Adverse Events (SAEs) Up to 6 years 1 month Phase 1b and Phase 2: Number of Participants With Anti-Cetrelimab Antibodies Up to 6 years 1 month Phase 1b: Plasma Concentration of Platinum (Cisplatin and Carboplatin) Chemotherapy Up to 6 years 1 month Phase 2: Duration of Response (DoR) Up to 6 years 1 month Phase 2: Overall Survival (OS) Up to 6 years 1 month Phase 2: Time to Response (TTR) Up to 6 years 1 month
Trial Locations
- Locations (127)
Grodno University Hospital
🇧🇾Grodno, Belarus
State Institution N.N. Alexandrov Republican Scientific and
🇧🇾Lesnoy, Belarus
Minsk city Clinical Oncological Dispensary
🇧🇾Minsk, Belarus
Mogilev Regional Hospital
🇧🇾Mogilev, Belarus
Vitebsk Regional Clinical Hospital
🇧🇾Vitebsk, Belarus
ULB Hôpital Erasme
🇧🇪Bruxelles, Belgium
Cliniques Universitaires Saint Luc
🇧🇪Bruxelles, Belgium
Jolimont
🇧🇪Haine-Saint-Paul, Belgium
Az Groeninge
🇧🇪Kortrijk, Belgium
CHU de Liège - Domaine Universitaire du Sart Tilman
🇧🇪Liege, Belgium
AZ Nikolaas - Campus Sint-Niklaas Moerland
🇧🇪Sint-Niklaas, Belgium
GZA Ziekenhuizen- Campus St Augustinus
🇧🇪Wilrijk, Belgium
Fundacao Pio XII
🇧🇷Barretos, Brazil
Santa Casa de Misericordia de Belo Horizonte
🇧🇷Belo Horizonte, Brazil
Liga Paranaense de Combate ao Cancer
🇧🇷Curitiba, Brazil
Oncocentro Servicos Medicos e Hospitalares Ltda - Oncocentro
🇧🇷Fortaleza, Brazil
Oncoclinicas Rio de Janeiro S A
🇧🇷Rio de Janeiro, Brazil
Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
🇧🇷Rio de Janeiro, Brazil
CEPHO Centro de Estudos e Pesquisa de Hematologia e Oncologia
🇧🇷Santo Andre, Brazil
Institut de Cancerologie de Ouest (ICO) Site Paul Papin
🇫🇷Angers Cedex 02, France
Hopital Saint André
🇫🇷Bordeaux, France
Centre Francois Baclesse
🇫🇷Caen, France
Centre Leon Berard
🇫🇷Lyon, France
APHM Hopital Timone
🇫🇷Marseille, France
Hopital Europeen Georges Pompidou
🇫🇷Paris, France
Clinique Sainte Anne
🇫🇷Strasbourg, France
CHRU de Tours
🇫🇷Tours, France
Clinical Diagnostic Centre of Nizhny Novgorod Region
🇷🇺Nizhny Novgorod, Russian Federation
Privolzhsky District Medical Centre
🇷🇺Nizhny Novgorod, Russian Federation
Private Medical Institution Euromedservice
🇷🇺Saint Petersburg, Russian Federation
Russian Scientific Center of Radiology and Surgical Technologies
🇷🇺Sankt-Peterburg, Russian Federation
Tambov Regional Oncology Clinical Dispansary
🇷🇺Tambov, Russian Federation
Multifunctional clinical medical center 'Medical city'
🇷🇺Tyumen, Russian Federation
Hosp. Del Mar
🇪🇸Barcelona, Spain
Hosp Clinic de Barcelona
🇪🇸Barcelona, Spain
Hosp. Univ. Ramon Y Cajal
🇪🇸Madrid, Spain
Hosp. Clinico San Carlos
🇪🇸Madrid, Spain
Hosp Univ Fund Jimenez Diaz
🇪🇸Madrid, Spain
Hosp Univ Hm Sanchinarro
🇪🇸Madrid, Spain
Hosp Virgen de La Victoria
🇪🇸Málaga, Spain
Complexo Hosp. Univ. de Ourense
🇪🇸Ourense, Spain
Complejo Hospitalario de Vigo
🇪🇸Pontevedra, Spain
Hosp. Quiron Madrid Pozuelo
🇪🇸Pozuelo de Alarcon, Spain
Corporacio Sanitari Parc Tauli
🇪🇸Sabadell, Spain
Hosp. Univ. Marques de Valdecilla
🇪🇸Santander, Spain
H. Clinico Universitario de Santiago de Compostela
🇪🇸Santiago de Compostela, Spain
Hosp. Virgen Macarena
🇪🇸Sevilla, Spain
Hosp. Virgen Del Rocio
🇪🇸Sevilla, Spain
Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
Hosp. Clinico Univ. de Valencia
🇪🇸Valencia, Spain
Centre hospitalier Saint Louis
🇫🇷La Rochelle Cedex 1, France
Cliniche Humanitas Gavazzeni
🇮🇹Bergamo, Italy
Istituto di Candiolo, IRCCS
🇮🇹Candiolo, Italy
Ospedale Di Zona B Ramazzini
🇮🇹Carpi, Italy
UOS Oncologia Medica, A.O. Cannizzaro
🇮🇹Catania, Italy
Arcispedale S. Anna Ferrara
🇮🇹Ferrara, Italy
PO A.Manzoni di Lecco, ASST Lecco - Oncologia Medica - Lecco
🇮🇹Lecco, Italy
Ospedale Civile Di Livorno
🇮🇹Livorno, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
ASST Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Clinical Oncology Dispensary
🇷🇺Omsk, Russian Federation
LLC Novaya Clinica
🇷🇺Pyatigorsk, Russian Federation
Adnan Menderes University Training and Research Hospital
🇹🇷Aydin, Turkey
Trakya University Medical Faculty
🇹🇷Edirne, Turkey
Istanbul University Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Royal Lancaster Infirmary
🇬🇧Lancaster, United Kingdom
St Bartholomew's Hospital
🇬🇧London, United Kingdom
White Plains Hospital Center for Cancer Care
🇺🇸White Plains, New York, United States
Gomel Regional Clinical Oncology Dispensary
🇧🇾Gomel, Belarus
Rocky Mountain Cancer Centers
🇺🇸Aurora, Colorado, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Maryland Oncology Hematology, PA
🇺🇸Rockville, Maryland, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Weill Cornell Medical College - NY Presbyterian Hospital
🇺🇸New York, New York, United States
Levine Cancer Institute, Carolinas HealthCare System
🇺🇸Charlotte, North Carolina, United States
Toledo Clinic Cancer Centers
🇺🇸Toledo, Ohio, United States
Penn State Hershey Cancer Institute
🇺🇸Hershey, Pennsylvania, United States
Texas Oncology, P.A.
🇺🇸Fort Worth, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Brest Regional Oncology Dispensary
🇧🇾Brest, Belarus
Institut de Cancerologie de Lorraine
🇫🇷Vandoeuvre lès Nancy, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Ospedale S. Maria Della Misericordia Centro Operativo Studi Clinici SC Oncologia Medica
🇮🇹Perugia, Italy
AUSL DI PIACENZA - Ospedale Guglielmo da Saliceto
🇮🇹Piacenza, Italy
Campus Bio Medico di Roma
🇮🇹Roma, Italy
Azienda Socio Sanitaria Territoriale (ASST) della Valtellin
🇮🇹Sondrio, Italy
Azienda Ospedaliera S. Maria Terni
🇮🇹Terni, Italy
Azienda Ospedaliero Universitaria S.Maria Della Misericordia
🇮🇹Udine, Italy
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
The Catholic university of Korea, St. Vincent's Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Kangbuk Samsung Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St Marys Hospital
🇰🇷Seoul, Korea, Republic of
Seoul Metropolitan Government Seoul National University Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
Pusan National University Yangsan Hospital
🇰🇷Yangsan-si, Korea, Republic of
Przychodnia Lekarska KOMED Roman Karaszewski
🇵🇱Konin, Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi
🇵🇱Lodz, Poland
LUX MED Onkologia Sp. z o.o.
🇵🇱Warszawa, Poland
Centralny Szpital Kliniczny MSWiA w Warszawie
🇵🇱Warszawa, Poland
Altai Regional Oncology Dispensary
🇷🇺Barnaul, Russian Federation
Ivanovo Regional Oncology Dispensary
🇷🇺Ivanovo, Russian Federation
GUZ Kursk Regional Oncology Dispensary
🇷🇺Kislino Village, Russian Federation
Leningrad Regional Oncology Dispensary
🇷🇺Kuzmolovsky, Russian Federation
City Clinical Hospital n.a. D.D.Pletnev
🇷🇺Moscow, Russian Federation
Russian Scientific Center of Roentgenoradiology
🇷🇺Moscow, Russian Federation
Moscow City Clinical Hospital # 62
🇷🇺Moscow, Russian Federation
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
Kaohsiung Medical University Chung Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung City, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
Chang-Gung Memorial Hospital, LinKou Branch
🇨🇳Taoyuan, Taiwan
Adana Acibadem Hospital
🇹🇷Adana, Turkey
Memorial Ankara Hastanesi
🇹🇷Ankara, Turkey
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital
🇹🇷Ankara, Turkey
Istanbul Medeniyet University Goztepe Training and Research Hospital
🇹🇷Istanbul, Turkey
Ege University
🇹🇷Izmir, Turkey
Kocaeli University Medical Faculty
🇹🇷Kocaeli, Turkey
Necmettin Erbakan University Meram Medical Faculty
🇹🇷Konya, Turkey
Karadeniz Teknik University Medical Faculty
🇹🇷Trabzon, Turkey
University College London Hospitals Nhs Foundation Trust
🇬🇧London, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom