Basket Trial in Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3- (FUZE Clinical Trial)

Solid Tumor Clinical Trial

Official title:

A Phase II Basket Study of the Oral Selective Pan-FGFR Inhibitor Debio 1347 in Subjects With Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03834220
• Other study ID #: Debio 1347-201
• Secondary ID: 2018-003584-53
• Status: Terminated
• Phase: Phase 2
• Start date: March 22, 2019
• Est. completion date: January 4, 2022

Study information

• Verified date: January 2024
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to assess the efficacy of Debio 1347 in terms of objective response rate (ORR) in participants with solid tumors harboring fibroblast growth factor receptor (FGFR)1-3 gene fusion/rearrangement.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 63
• Est. completion date: January 4, 2022
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cytologically or histologically confirmed advanced solid tumor
• Radiographic progression on prior systemic therapy; prior localized therapy (i.e., radiation, ablation, embolization) is allowed provided radiographic progression out-of-field or in the treatment, field is shown
• Locally-advanced (unresectable) or metastatic disease harboring an FGFR1-3 gene fusion/rearrangement potentially leading to a functional FGFR aberrant protein, identified through local and/or central molecular assay

Exclusion Criteria:

• History of hypersensitivity to any of the excipients in the Debio 1347 formulation
• History and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes, lung nodules and asymptomatic vascular or cartilage/tendon calcifications
• Administration of any investigational agent within 2 weeks prior to initial dosing with Debio 1347 (3 weeks for immune checkpoint inhibitors)

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• Debio 1347
Debio 1347 oral tablets.

Locations

Country	Name	City	State
Australia	Southern Highlands Private Hospital	Bowral
Australia	Peninsula and Southeast Oncology (PASO)	Frankston
Australia	Linear Clinical Research, B Block Sir Charles Gairdner Hospital	Nedlands
Australia	John Flynn Private Hospital	Tugun
Austria	LKH - Universitätsklinikum der PMU Salzburg	Salzburg
Austria	Landesklinikum Wiener Neustadt	Wiener Neustadt
Brazil	Hospital de Caridade de Ijuí, Avenida David J Martins	Ijuí
Brazil	Hospital de Clínicas de Porto Alegre	Rio Grande
Brazil	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia	Santo André
Brazil	ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira, Avenida Doutor Arnaldo	São Paulo
Bulgaria	MHAT - Dobrich	Dobrich
Bulgaria	Complex Oncological Center - Plovdiv, EOOD	Plovdiv
Bulgaria	MHAT "Serdika", EOOD	Sofia
Croatia	General Hospital Varazdin	Varaždin
Croatia	University Hospital Centre, Sestre Milosrdnice	Zagreb
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Králové
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Thomayerova nemocnice	Prague
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha
Denmark	Ålborg Universitets Hospital	Aalborg
Denmark	Herlev Hospital	Herlev
Denmark	Odense Universitetshospital	Odense
Finland	Docrates Syöpäsairaala	Helsinki
Finland	Helsinki University Hospital	Helsinki
France	ICO - Site Paul Papin	Angers
France	CHU Bordeaux - Hôpital Saint André, Groupe Hospitalier Sud - Hôpital Haut-Lévêque	Bordeaux
France	Centre Oscar Lambret	Lille
France	Groupe Hospitalier Sud - Hôpital Haut Lévêque	Pessac
France	ICO - Site René Gauducheau	Saint-Herblain
France	Institut Gustave Roussy	Villejuif
Greece	General Hospital of Athens "Alexandra"	Athens
Greece	General Hospital of Athens Laiko	Athens
Greece	General Hospital of Athens of Chest Diseases "SOTIRIA"	Athens
Greece	University General Hospital of Ioannina	Ioánnina
Korea, Republic of	Seoul National University Bundang Hospital, Department of Oncology Medical office	Gyeonggi-do
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital, CRC Room, 3F	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center, CRC Room, 18F, Artificial intelligence hospital	Incheon
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Seoul National University Hospital (SNUH)	Seoul
Korea, Republic of	Ajou University Hospital, CRC room, Clinical Trial Center	Suwon
Netherlands	VU Medisch Centrum	Amsterdam
Netherlands	Haga Ziekenhuis	Den Haag
Norway	Akershus University Hospital	Lørenskog
Norway	Radiumhospitalet, Montebello	Oslo
Philippines	Cebu Doctors' University Hospital (CDUH), Research Office	Cebu City
Philippines	Philippine General Hospital, Clinical Trial Unit Room 5, Medical Research Laboratory	Ermita
Philippines	St. Luke's Medical Center, Human Cancer Biobank Research Center	Quezon City
Poland	Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu	Poznan
Poland	Centrum Onkologii-Instytut im.M.Sklodowskiej Curie	Warszawa
Poland	MTZ Clinical Research	Warszawa
Romania	S.C Delta Health Care S.R.L	Bucuresti
Romania	S.C Medisprof S.R.L.	Cluj-Napoca
Romania	S.C Centrul de Oncologie Sf. Nectarie S.R.L.	Craiova
Romania	S.C Oncocenter Oncologie Clinica S.R.L.	Timisoara
Russian Federation	SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"	Arkhangel'sk
Russian Federation	TSBHI "Altai Territorial oncological dispensary"	Barnaul
Russian Federation	LLC Evimed	Chelyabinsk
Russian Federation	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow
Russian Federation	BHI of Omsk region "Clinical Oncology Dispensary"	Omsk
Russian Federation	Tomsk Research Instutite of Oncology	Tomsk
Singapore	Singapore National Cancer Center (SNCC)	Singapore
Singapore	Tan Tock Seng Hospital, Communicable Disease Centre	Singapore
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
Taiwan	Shuang Ho Hospital	New Taipei City
Taiwan	Taichung Veterans General Hospital, The Radiation Oncology Department	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Medical University Hospital (TMUH)	Taipei
Taiwan	Taipei Veterans General Hospital, Medical Science & Technology Building	Taipei
Taiwan	Linkou Chang-Gung Memorial Hospital	Taoyuan
Ukraine	CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU	Dnipro
Ukraine	Communal Non-profit Enterprise Regional Center of Oncology	Kharkiv
Ukraine	SI V.T. Zaycev Institute of general & urgent surgery of National academy medical sciences of Ukraine, Department of purulent surgery	Kharkiv
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Guy's Hospital	London
United Kingdom	Hammersmith Hospital	London
United Kingdom	The Christie	Manchester
United States	University of Michigan	Ann Arbor	Michigan
United States	The John Hopkins Hospital	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	UC Health, LLC.	Cincinnati	Ohio
United States	The Ohio State University Wexner Medical Center - James Cancer Hospital	Columbus	Ohio
United States	Memorial Sloan Kettering Cancer Center	Harrison	New York
United States	MD Anderson Cancer Center	Houston	Texas
United States	Moores UCSD Cancer Center	La Jolla	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	Memorial Sloan Kettering Cancer Center	Middletown	New Jersey
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Tulane University Cancer Center	New Orleans	Louisiana
United States	Memorial Sloan-Kettering Hospital	New York	New York
United States	West Penn - Allegheny Oncology Network	Pittsburgh	Pennsylvania
United States	University of Utah Hospitals & Clinics	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California
United States	Sarcoma Oncology Center	Santa Monica	California
United States	Ironwood Cancer & Research Centers - Scottsdale	Scottsdale	Arizona
United States	Fred Hutchinson/Seattle Care Alliance	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute, Inc	Tampa	Florida
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	CTCA Cancer Treatment Centers	Tulsa	Oklahoma

Sponsors (3)

Lead Sponsor	Collaborator
Debiopharm International SA	Caris Life Sciences, Optimal Research (Just In Time sites)

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  Bulgaria,  Croatia,  Czechia,  Denmark,  Finland,  France,  Greece,  Korea, Republic of,  Netherlands,  Norway,  Philippines,  Poland,  Romania,  Russian Federation,  Singapore,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) as Centrally Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria	ORR was defined as the percentage of participants with a best overall response (BOR) of partial or complete response (PR or CR). BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as =30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to disease progression or end of study (up to 1 year and 9 months)
Secondary	Duration of Response (DOR) as Centrally Measured by Independent Review Committee (IRC)	DOR was defined as the time from the date of the initial PR or CR to date of the first documented progression or death due to any cause. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as =30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to disease progression or end of study (up to 2 years and 9 months)
Secondary	Disease Control Rate (DCR) as Centrally Measured by Independent Review Committee (IRC)	DCR was defined as the percentage of participants with a BOR of confirmed CR, confirmed PR or stable disease (SD) =6 weeks. BOR was defined as the best confirmed response observed from first administration of study drug until disease progression. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as =30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD was defined as = 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.	Up to disease progression or end of study (up to 2 years and 9 months)
Secondary	Progression-Free Survival (PFS) as Centrally Measured by Independent Review Committee (IRC)	PFS was defined as the time from the start date of treatment to date of the first documented progression or death due to any cause.	From the start of the study up to disease progression or death (up to 2 years and 9 months)
Secondary	Overall Survival (OS)	OS was defined as the time from the start date of treatment to date of death due to any cause. Participants with no documented death were censored at the last date known to be alive.	Until death or loss to follow-up or end of study (up to 2 years and 9 months)
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by National Cancer Institute Common Terminology Criteria (NCI CTCAE) v5.0 and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant or clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A TEAE is defined as an AE that either starts or worsens in severity on or after the first administration of the study drug and within 30 days of the last administration of the study drug. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.	From first dose of study drug up to 30 days post last dose (Up to 2 years and 9 months)
Secondary	Trough Concentration at Steady State (Ctrough,ss) of Debio 1347 in Plasma	Geometric mean and geometric percent CV summary was estimated based on log-linear model.	Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days)
Secondary	Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Debio 1347 in Plasma	Geometric mean and geometric percent CV summary was estimated based on log-linear model.	Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days)
Secondary	Correlation of Debio 1347 Plasma Concentration (C) and QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF)		Pre-dose on Days 14 and 28, and 1, 3, 7 hours post-dose on Day 28 of Cycle 1; pre-dose on Days 14 and 28, and 3 hours post-dose on Day 28 of Cycle 2 (each cycle length = 28 days)