Clinical trial NCT03473743: A Study of Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial Cancer
Official title: A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Urothelial Carcinoma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-03-22
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs)
timeFrame: Up to 8 weeks
measure: Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment
timeFrame: From Day 1 up to 36 months
measure: Phase 2: Number of Participants With Treatment-emergent Adverse Event (TEAEs)
timeFrame: From Day 1 up to 36 months
Secondary outcomes:
measure: Phase 1b and Phase 2: Plasma Concentration of Erdafitinib
timeFrame: Up to 6 years 1 month
measure: Phase 1b and Phase 2: Serum Concentration of Cetrelimab
timeFrame: Up to 6 years 1 month
measure: Phase 1b: Plasma Concentration of Platinum (Cisplatin and Carboplatin) Chemotherapy
timeFrame: Up to 6 years 1 month
measure: Phase 1b and Phase 2: Number of Participants With Anti-Cetrelimab Antibodies
timeFrame: Up to 6 years 1 month
measure: Phase 2: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to 6 years 1 month
measure: Phase 2: Number of Participants With Abnormal Laboratory Values
timeFrame: Up to 6 years 1 month
measure: Phase 2: Duration of Response (DoR)
timeFrame: Up to 6 years 1 month
measure: Phase 2: Time to Response (TTR)
timeFrame: Up to 6 years 1 month
measure: Phase 2: Progression-free Survival (PFS)
timeFrame: Up to 6 years 1 month
measure: Phase 2: Overall Survival (OS)
timeFrame: Up to 6 years 1 month
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Rockville
country: United States
facility: Maryland Oncology Hematology, PA
state: Maryland
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical College - NY Presbyterian Hospital
state: New York
city: White Plains
country: United States
facility: White Plains Hospital Center for Cancer Care
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute, Carolinas HealthCare System
state: North Carolina
city: Toledo
country: United States
facility: Toledo Clinic Cancer Centers
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute
state: Pennsylvania
city: Fort Worth
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Brest
country: Belarus
facility: Brest Regional Oncology Dispensary
city: Gomel
country: Belarus
facility: Gomel Regional Clinical Oncology Dispensary
city: Grodno
country: Belarus
facility: Grodno University Hospital
city: Lesnoy
country: Belarus
facility: State Institution N.N. Alexandrov Republican Scientific and
city: Minsk
country: Belarus
facility: Minsk city Clinical Oncological Dispensary
city: Mogilev
country: Belarus
facility: Mogilev Regional Hospital
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Hospital
city: Bruxelles
country: Belgium
facility: ULB Hôpital Erasme
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Haine-Saint-Paul
country: Belgium
facility: Jolimont
city: Kortrijk
country: Belgium
facility: Az Groeninge
city: Liege
country: Belgium
facility: CHU de Liège - Domaine Universitaire du Sart Tilman
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas - Campus Sint-Niklaas Moerland
city: Wilrijk
country: Belgium
facility: GZA Ziekenhuizen- Campus St Augustinus
city: Barretos
country: Brazil
facility: Fundacao Pio XII
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
city: Curitiba
country: Brazil
facility: Liga Paranaense de Combate ao Cancer
city: Fortaleza
country: Brazil
facility: Oncocentro Servicos Medicos e Hospitalares Ltda - Oncocentro
city: Rio de Janeiro
country: Brazil
facility: Oncoclinicas Rio de Janeiro S A
city: Rio de Janeiro
country: Brazil
facility: Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
city: Santo Andre
country: Brazil
facility: CEPHO Centro de Estudos e Pesquisa de Hematologia e Oncologia
city: Angers Cedex 02
country: France
facility: Institut de Cancerologie de Ouest (ICO) Site Paul Papin
city: Bordeaux
country: France
facility: Hopital Saint André
city: Caen
country: France
facility: Centre Francois Baclesse
city: La Rochelle Cedex 1
country: France
facility: Centre hospitalier Saint Louis
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: APHM Hopital Timone
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Strasbourg
country: France
facility: Clinique Sainte Anne
city: Tours
country: France
facility: CHRU de Tours
city: Vandoeuvre lès Nancy
country: France
facility: Institut de Cancerologie de Lorraine
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Bergamo
country: Italy
facility: Cliniche Humanitas Gavazzeni
city: Candiolo
country: Italy
facility: Istituto di Candiolo, IRCCS
city: Carpi
country: Italy
facility: Ospedale Di Zona B Ramazzini
city: Catania
country: Italy
facility: UOS Oncologia Medica, A.O. Cannizzaro
city: Ferrara
country: Italy
facility: Arcispedale S. Anna Ferrara
city: Lecco
country: Italy
facility: PO A.Manzoni di Lecco, ASST Lecco - Oncologia Medica - Lecco
city: Livorno
country: Italy
facility: Ospedale Civile Di Livorno
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Perugia
country: Italy
facility: Ospedale S. Maria Della Misericordia Centro Operativo Studi Clinici SC Oncologia Medica
city: Piacenza
country: Italy
facility: AUSL DI PIACENZA - Ospedale Guglielmo da Saliceto
city: Roma
country: Italy
facility: Campus Bio Medico di Roma
city: Sondrio
country: Italy
facility: Azienda Socio Sanitaria Territoriale (ASST) della Valtellin
city: Terni
country: Italy
facility: Azienda Ospedaliera S. Maria Terni
city: Udine
country: Italy
facility: Azienda Ospedaliero Universitaria S.Maria Della Misericordia
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: The Catholic university of Korea, St. Vincent's Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Marys Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Metropolitan Government Seoul National University Boramae Medical Center
city: Yangsan-si
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED Roman Karaszewski
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi
city: Warszawa
country: Poland
facility: LUX MED Onkologia Sp. z o.o.
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA w Warszawie
city: Barnaul
country: Russian Federation
facility: Altai Regional Oncology Dispensary
city: Ivanovo
country: Russian Federation
facility: Ivanovo Regional Oncology Dispensary
city: Kislino Village
country: Russian Federation
facility: GUZ Kursk Regional Oncology Dispensary
city: Kuzmolovsky
country: Russian Federation
facility: Leningrad Regional Oncology Dispensary
city: Moscow
country: Russian Federation
facility: City Clinical Hospital n.a. D.D.Pletnev
city: Moscow
country: Russian Federation
facility: Russian Scientific Center of Roentgenoradiology
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital # 62
city: Nizhny Novgorod
country: Russian Federation
facility: Clinical Diagnostic Centre of Nizhny Novgorod Region
city: Nizhny Novgorod
country: Russian Federation
facility: Privolzhsky District Medical Centre
city: Omsk
country: Russian Federation
facility: Clinical Oncology Dispensary
city: Pyatigorsk
country: Russian Federation
facility: LLC Novaya Clinica
city: Saint Petersburg
country: Russian Federation
facility: Private Medical Institution Euromedservice
city: Sankt-Peterburg
country: Russian Federation
facility: Russian Scientific Center of Radiology and Surgical Technologies
city: Tambov
country: Russian Federation
facility: Tambov Regional Oncology Clinical Dispansary
city: Tyumen
country: Russian Federation
facility: Multifunctional clinical medical center 'Medical city'
city: Barcelona
country: Spain
facility: Hosp. Del Mar
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Clinico San Carlos
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Madrid
country: Spain
facility: Hosp Univ Hm Sanchinarro
city: Málaga
country: Spain
facility: Hosp Virgen de La Victoria
city: Ourense
country: Spain
facility: Complexo Hosp. Univ. de Ourense
city: Pontevedra
country: Spain
facility: Complejo Hospitalario de Vigo
city: Pozuelo de Alarcon
country: Spain
facility: Hosp. Quiron Madrid Pozuelo
city: Sabadell
country: Spain
facility: Corporacio Sanitari Parc Tauli
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Santiago de Compostela
country: Spain
facility: H. Clinico Universitario de Santiago de Compostela
city: Sevilla
country: Spain
facility: Hosp. Virgen Macarena
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Valencia
country: Spain
facility: Hosp. Clinico Univ. de Valencia
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung Ho Memorial Hospital
city: Taichung City
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang-Gung Memorial Hospital, LinKou Branch
city: Adana
country: Turkey
facility: Adana Acibadem Hospital
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Ankara
country: Turkey
facility: Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital
city: Aydin
country: Turkey
facility: Adnan Menderes University Training and Research Hospital
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul Medeniyet University Goztepe Training and Research Hospital
city: Izmir
country: Turkey
facility: Ege University
city: Kocaeli
country: Turkey
facility: Kocaeli University Medical Faculty
city: Konya
country: Turkey
facility: Necmettin Erbakan University Meram Medical Faculty
city: Trabzon
country: Turkey
facility: Karadeniz Teknik University Medical Faculty
city: Lancaster
country: United Kingdom
facility: Royal Lancaster Infirmary
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: University College London Hospitals Nhs Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: