A Study of Erdafitinib in Participants With Advanced Solid Tumors and Fibroblast Growth Factor Receptor (FGFR) Gene Alterations

Advanced Solid Tumor Clinical Trial

— RAGNAR  

Official title:

A Phase 2 Study of Erdafitinib in Subjects With Advanced Solid Tumors and FGFR Gene Alterations

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04083976
• Other study ID #: CR108661
• Secondary ID: 2019-002113-1942
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 20, 2019
• Est. completion date: September 20, 2024

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of erdafitinib in terms of overall response rate (ORR) in adult and pediatric participants with advanced solid tumors with fibroblast growth factor receptor (FGFR) alterations (mutations or gene fusions). It will also evaluate ORR in pediatric participants with advanced solid tumors and FGFR alterations.

Description:

Erdafitinib is a selective and potent pan FGFR 1-4 inhibitor with demonstrated clinical activity in participants with metastatic urothelial cancer and cholangiocarcinoma identified to have alterations in the FGFR pathway. This study targets the underlying altered biology of FGFR-driven tumors irrespective of solid tumor histology subtype. The study consists of screening phase, treatment phase and the post treatment follow-up phase (from the end of treatment visit until the participant has died, withdraws consent, is lost to follow-up, or the end of study, whichever comes first). End of study is considered as the time when the last participant receives the last dose of study drug on the study and either all pediatric participants are off study or until the most recently enrolled pediatric participant still participating in the study has 6 months of follow-up, whichever occurs first. Currently this study is recruiting pediatric participants only.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 316
• Est. completion date: September 20, 2024
• Est. primary completion date: December 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• Histologic demonstration of an unresectable, locally advanced, or metastatic solid tumor malignancy with an fibroblast growth factor receptor (FGFR) mutation or FGFR gene fusion

• Measurable disease

• Participant must have received at least one prior line of systemic therapy in the advanced, unresectable, or metastatic setting; or is a child or adolescent participant with a newly-diagnosed solid tumor and no acceptable standard therapies

• Documented progression of disease, defined as any progression that requires a change in treatment, prior to full study screening

Exclusion Criteria:

• Has had prior chemotherapy, targeted therapy, or treatment with an investigational anticancer agent within 15 days or less than or equal to (<=) 5 half-lives of the agent (whichever is longer) and up to a maximum of 30 days before the first dose of erdafitinib

• The presence of FGFR gatekeeper and resistance mutations

• Histologic demonstration of urothelial carcinoma

• Hematologic malignancy (i.e., myeloid and lymphoid neoplasms

• For non-small cell lung cancer participants only: pathogenic somatic mutations or gene fusions in the following genes: EGFR, ALK, ROS1, NTRK, BRAF V600E and KRAS

• Active malignancies other than for disease requiring therapy

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• Erdafitinib
Participants will receive erdafitinib oral tablets.

Locations

Country	Name	City	State
Argentina	Hospital Aleman	Buenos Aires
Argentina	CEMIC Saavedra	Ciudad Autonoma de Buenos Aires
Argentina	Centro Oncológico Korben	Ciudad Autonoma de Buenos Aires
Argentina	Instituto Fleni	Ciudad Autonoma de Buenos Aires
Argentina	Instituto de Investigaciones Metabólicas	Ciudad Autónoma de Buenos Aires
Argentina	Cemaic - Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica	Cordoba
Argentina	Hospital Italiano de La Plata	La Plata Lpl Lpl
Argentina	Hospital Privado de Comunidad	Mar Del Plata
Argentina	Instituto de Investigaciones Clinicas Mar del Plata	Mar Del Plata, Buenos Aires
Argentina	Hospital Universitario Austral	Pilar
Argentina	Sanatorio Britanico de Rosario	Rosario
Argentina	ARS Médica	San Salvador De Jujuy
Australia	Flinders Centre for Innovation in Cancer	Adelaide
Australia	Chris O'Brien Lifehouse	Camperdown
Australia	St Vincent s Hospital Sydney	Darlinghurst
Australia	St Vincents Hospital Melbourne	Fitzroy
Australia	Fiona Stanley Hospital	Murdoch
Australia	Intergrated Clinical Oncology Network Pty Ltd (ICON)	South Brisbane
Belgium	AZ Klina	Brasschaat
Belgium	UCL Hopital Saint-Luc	Bruxelles
Belgium	Grand Hopital de Charleroi, site Notre Dame	Charleroi
Belgium	CHU UCL Namur - Site Dinant	Dinant
Belgium	UZA	Edegem
Belgium	AZ Maria Middelares	Gent
Belgium	UZ Gent	Gent
Belgium	Jolimont	Haine-Saint-Paul, La Louviere
Belgium	CHU UCL Namur - Site Sainte Elisabeth	Namur
Belgium	Cliniques St Pierre	Ottignies
Belgium	CHU UCL Namur - Site Godinne	Yvoir
Brazil	Fundacao Pio XII	Barretos
Brazil	Liga Paranaense de Combate ao Cancer	Curitiba
Brazil	Associacao de Combate ao Cancer em Goias - Hospital de Cancer Araujo Jorge	Goiania
Brazil	Associacao Hospital de Caridade Ijui	Ijui
Brazil	Liga Norte Riograndense Contra O Cancer	Natal
Brazil	Irmandade Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Instituto de Medicina Integral Professor Fernando Figueira	Recife
Brazil	Instituto D Or de Pesquisa e Ensino (IDOR)	Rio de Janeiro
Brazil	Oncoclinicas Rio de Janeiro S A	Rio de Janeiro
Brazil	Hospital Sao Rafael	Salvador
Brazil	Fundacao Antonio Prudente A C Camargo Cancer Center	Sao Paulo
Brazil	Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo	Sao Paulo
Brazil	GRAACC	São Paulo
Brazil	Hospital Das Clinicas Da Faculdade De Medicina Da USP	São Paulo
Brazil	Real e Benemerita Associacao Portuguesa de Beneficencia	São Paulo
Brazil	Sociedade Beneficente de Senhoras - Hospital Sírio Libanês	São Paulo
China	Beijing Luhe Hospital, Capital Medical University	Beijing
China	Beijing Tiantan Hospital, Capital Medical University	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing
China	Chinese PLA General Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	Jilin cancer hospital	Changchun
China	The First Hospital of Jilin University	Changchun
China	West China Hospital,Sichuan University	Chengdu
China	Chongqing Southwest Hospital	Chongqing
China	Third Military Medical University Daping Hospital Cancer Center	Chongqing
China	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University	Guangzhou
China	First affiliated Hospital of Zhejiang University	Hangzhou
China	Zhejiang Cancer Hospital	Hangzhou
China	Eastern Theater General Hospital, Qinhuai District Medical Area	Nanjing
China	Cancer Hospital, FuDan University	Shanghai
China	Huashan Hospital Fudan University	Shanghai
China	Ruijin Hospital Shanghai Jiao Tong University	Shanghai
China	Shanghai Zhongshan Hospital	Shanghai
France	Hopital Saint André	Bordeaux
France	Centre Francois Baclesse	Caen
France	Centre Jean Perrin	Clermont Ferrand
France	Centre Georges François Leclerc	Dijon
France	Centre Oscar Lambret	Lille
France	Centre Leon Berard	Lyon
France	Hopital de la Timone	Marseille
France	Institut Curie	Paris
France	CHU De Poitiers	Poitiers
France	Institut de Cancérologie de Lorraine	Vandoeuvre lès Nancy
France	Institut Gustave Roussy	Villejuif
Germany	Charité	Berlin
Germany	Medizinische Fakultat Carl Gustav Carus Technische Universitat Dresden	Dresden
Germany	Universitaetsklinikum Essen	Essen
Germany	Universitaetsklinikum Frankfurt	Frankfurt
Germany	Asklepios Klinik Altona	Hamburg
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Koeln	Köln
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Klinikum rechts der Isar der TU Munchen	München
Germany	Universitatsklinikum Tubingen	Tübingen
Italy	Istituto Ortopedico Rizzoli	Bologna
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	ASST di Monza	Monza
Italy	Azienda Ospedaliera Univ.- Università Degli studi della Campania - Luigi Vanvitelli	Napoli
Italy	Fondazione G Pascale Istituto Nazionale Tumori IRCCS	Napoli
Italy	Ospedale S. Maria Della Misericordia	Perugia
Italy	Ospedale Santa Chiara AO Universitaria Pisana	Pisa
Italy	Azienda Ospedaliera S. Maria Terni	Terni
Italy	Ospedale Borgo Roma	Verona
Japan	National Cancer Center Hospital	Chuo Ku
Japan	Hiroshima University Hospital	Hiroshima shi
Japan	National Cancer Center Hospital East	Kashiwa
Japan	National Hospital Organizaiton Shikoku Cancer Center	Matsuyama
Japan	Fujita Health University Hospital	Toyoake
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul
Poland	Centrum Onkologii im. Prof. F. Lukaszczyka w Bydgoszczy	Bydgoszcz
Poland	Przychodnia Lekarska KOMED Roman Karaszewski	Konin
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie	Krakow
Poland	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi	Lodz
Poland	Centrum Medyczne Pratia Poznan	Skorzewo
Poland	Centralny Szpital Kliniczny MSWiA w Warszawie	Warszawa
Poland	Instytut Matki i Dziecka	Warszawa
Poland	Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy	Warszawa
Spain	Hosp Clinic de Barcelona	Barcelona
Spain	Hosp. Sant Joan de Deu	Barcelona
Spain	Hosp. Univ. Quiron Dexeus	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Inst. Cat. Doncologia-H Duran I Reynals	Hospitalet de Llobregat, Barcelona
Spain	Clinica Univ. de Navarra	Madrid
Spain	Hosp Univ Fund Jimenez Diaz	Madrid
Spain	Hosp. Infantil Univ. Nino Jesus	Madrid
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. La Paz	Madrid
Spain	Hosp. Univ. Ramon Y Cajal	Madrid
Spain	Hosp. Virgen Del Rocio	Sevilla
Spain	Hosp. Clinico Univ. de Valencia	Valencia
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Chang Gung Medical Foundation	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	E-Da Cancer Hospital	Kaohsiung City
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Chi Mei Medical Center Liu Ying	Tainan
Taiwan	Chi Mei Medical Center Yong Kang	Tainan
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital Linkou Branch	Taoyuan City
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Bristol Royal Hospital for Children	Bristol
United Kingdom	The Christie Nhs Foundation Trust	Manchester
United Kingdom	Freeman Hospital	Newcastle upon Tyne
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	The Royal Marsden NHS Trust	Sutton
United Kingdom	The Clatterbridge Cancer Centre	Wirral
United States	Hawaii Cancer Care	'Aiea	Hawaii
United States	Emory University	Atlanta	Georgia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Levine Cancer Institute, Carolinas HealthCare System	Charlotte	North Carolina
United States	Tennessee Oncology, PLLC	Chattanooga	Tennessee
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Rocky Mountain Cancer Centers	Colorado Springs	Colorado
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Texas Oncology-Fort Worth Cancer Center	Fort Worth	Texas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Memorial Cancer Institute	Hollywood	Florida
United States	MD Anderson	Houston	Texas
United States	Oncology Consultants - Texas	Houston	Texas
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai	New York	New York
United States	Texas Oncology Odessa-West Texas Cancer Center	Odessa	Texas
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Texas Oncology San Antonio Northeast	San Antonio	Texas
United States	Maine Medical Center	Scarborough	Maine
United States	NorthWest Medical Specialties, PLLC	Tacoma	Washington
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	Aurora Research Institute	Wauwatosa	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  China,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR) as Assessed by Independent Review Committee (IRC)	ORR as assessed by IRC is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR).	Up to 6 years and 9 months
Secondary	Overall Response Rate as Assessed by Investigator	ORR as assessed by investigator is defined as the percentage of participants who achieve a CR or PR.	Up to 6 years and 9 months
Secondary	Duration of Response (DOR)	DOR is the duration from the date of initial documentation of a response to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study), or death, whichever comes first.	Up to 6 years and 9 months
Secondary	Disease Control Rate (DCR)	DCR is defined as the percentage of participants with CR, PR or stable disease (SD).	Up to 6 years and 9 months
Secondary	Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with CR, PR or durable SD.	Up to 6 years and 9 months
Secondary	Progression Free Survival (PFS)	PFS is the duration from the date of the first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first.	Up to 6 years and 9 months
Secondary	Overall Survival (OS)	OS will be measured from the date of first dose of study drug to the date of the participant's death.	Up to 6 years and 9 months
Secondary	Plasma Concentrations of Erdafitinib	Plasma concentrations of erdafitinib will be reported.	Predose and 2-4 hours postdose
Secondary	Number of Participants with Adverse Events (AEs)	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the relevant investigational product.	Up to 6 years and 9 months
Secondary	Number of Participants with Adverse Events by Severity	An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Adverse event severity is a clinical determination of the intensity of an adverse event.	Up to 6 years and 9 months
Secondary	Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score	The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.	Baseline; up to 2 years and 9 months
Secondary	Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score	The PGIS is a single question regarding the patient report of disease severity: considering all aspects of your cancer symptoms right now would you say your cancer symptoms are none, mild, moderate, severe, or very severe?	Baseline; up to 2 years and 9 months
Secondary	Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Change (PGIC) Scale	The PGIC is the patient-reported outcome (PRO) counterpart to the clinical global impressions (CGI) scale. The PGIC is a single verbal rating scale ranging from 1 = a lot better now to 7 = a lot worse now.	Baseline; up to 2 years and 9 months
Secondary	Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Score	The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).	Baseline; up to 2 years and 9 months
Secondary	Change from Baseline in Pediatric Functional Assessment of Cancer Therapy - Brain (Peds FACT-Br) Total Score	Peds FACT-Br consists of 4 sets of disease-specific questions pertaining to brain neoplasms (a set of 34 to 37 questions each for child, parent of child, adolescent or parent of adolescent). Peds FACT-Br total score for child ranges from 0-136 and for parent of child, adolescent and parent of adolescent the score ranges from 0-148. Here '0' indicates a severely "symptomatic participant" and highest score indicates "asymptomatic participant".	Baseline; up to 2 years and 9 months