Basket Trial in Solid Tumors Harboring a Fusion of FGFR1, FGFR2 or FGFR3- (FUZE Clinical Trial)
- Conditions
- Solid Tumor
- Interventions
- Drug: Debio 1347
- Registration Number
- NCT03834220
- Lead Sponsor
- Debiopharm International SA
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 63
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2: Debio 1347 (Urothelial Cancer) Debio 1347 Participants with urothelial cancer were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 5.86 weeks). Cohort 1: Debio 1347 (Biliary Tract Cancer) Debio 1347 Participants with biliary tract cancer were included in this cohort to receive Debio 1347 80 milligrams (mg) tablets, orally, once daily (QD), from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 20 weeks). Cohort 3: Debio 1347 (All Other Solid Tumor Histologies) Debio 1347 Participants with all other solid tumor histologies were included in this cohort to receive Debio 1347 80 mg tablets, orally, QD, from Day 1 to Day 28 in 28-day cycles until the occurrence of disease progression or unacceptable toxicity (up to a median duration of 8.14 weeks).
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) as Centrally Measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria Up to disease progression or end of study (up to 1 year and 9 months) 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) as Centrally Measured by Independent Review Committee (IRC) Up to disease progression or end of study (up to 2 years and 9 months) 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.
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) From first dose of study drug up to 30 days post last dose (Up to 2 years and 9 months) 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.
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval at Steady State (AUCtau,ss) of Debio 1347 in Plasma Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days) Geometric mean and geometric percent CV summary was estimated based on log-linear model.
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) Progression-Free Survival (PFS) as Centrally Measured by Independent Review Committee (IRC) From the start of the study up to disease progression or death (up to 2 years and 9 months) 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.
Disease Control Rate (DCR) as Centrally Measured by Independent Review Committee (IRC) Up to disease progression or end of study (up to 2 years and 9 months) 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.
Overall Survival (OS) Until death or loss to follow-up or end of study (up to 2 years and 9 months) 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.
Trough Concentration at Steady State (Ctrough,ss) of Debio 1347 in Plasma Predose and post dose up to Cycle 2 Day 28 (each cycle length = 28 days) Geometric mean and geometric percent CV summary was estimated based on log-linear model.
Trial Locations
- Locations (104)
CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU
🇺🇦Dnipro, Ukraine
The Ohio State University Wexner Medical Center - James Cancer Hospital
🇺🇸Columbus, Ohio, United States
ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira, Avenida Doutor Arnaldo
🇧🇷São Paulo, Brazil
Groupe Hospitalier Sud - Hôpital Haut Lévêque
🇫🇷Pessac, France
S.C Medisprof S.R.L.
🇷🇴Cluj-Napoca, Romania
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
The Christie
🇬🇧Manchester, United Kingdom
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson/Seattle Care Alliance
🇺🇸Seattle, Washington, United States
ICO - Site Paul Papin
🇫🇷Angers, France
UC Health, LLC.
🇺🇸Cincinnati, Ohio, United States
University of Utah Hospitals & Clinics
🇺🇸Salt Lake City, Utah, United States
Ironwood Cancer & Research Centers - Scottsdale
🇺🇸Scottsdale, Arizona, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
H. Lee Moffitt Cancer Center and Research Institute, Inc
🇺🇸Tampa, Florida, United States
James Graham Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
The John Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Tulane University Cancer Center
🇺🇸New Orleans, Louisiana, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Memorial Sloan-Kettering Hospital
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸Harrison, New York, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
West Penn - Allegheny Oncology Network
🇺🇸Pittsburgh, Pennsylvania, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Southern Highlands Private Hospital
🇦🇺Bowral, Australia
Peninsula and Southeast Oncology (PASO)
🇦🇺Frankston, Australia
LKH - Universitätsklinikum der PMU Salzburg
🇦🇹Salzburg, Austria
Linear Clinical Research, B Block Sir Charles Gairdner Hospital
🇦🇺Nedlands, Australia
John Flynn Private Hospital
🇦🇺Tugun, Australia
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
🇧🇷Santo André, Brazil
Landesklinikum Wiener Neustadt
🇦🇹Wiener Neustadt, Austria
Hospital de Caridade de Ijuí, Avenida David J Martins
🇧🇷Ijuí, Brazil
Hospital de Clínicas de Porto Alegre
🇧🇷Rio Grande, Brazil
MHAT - Dobrich
🇧🇬Dobrich, Bulgaria
Complex Oncological Center - Plovdiv, EOOD
🇧🇬Plovdiv, Bulgaria
MHAT "Serdika", EOOD
🇧🇬Sofia, Bulgaria
General Hospital Varazdin
🇭🇷Varaždin, Croatia
University Hospital Centre, Sestre Milosrdnice
🇭🇷Zagreb, Croatia
Fakultni nemocnice u sv. Anny v Brne
🇨🇿Brno, Czechia
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Králové, Czechia
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Herlev Hospital
🇩🇰Herlev, Denmark
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha, Czechia
Thomayerova nemocnice
🇨🇿Prague, Czechia
Ålborg Universitets Hospital
🇩🇰Aalborg, Denmark
Docrates Syöpäsairaala
🇫🇮Helsinki, Finland
Odense Universitetshospital
🇩🇰Odense, Denmark
Helsinki University Hospital
🇫🇮Helsinki, Finland
Institut Gustave Roussy
🇫🇷Villejuif, France
CHU Bordeaux - Hôpital Saint André, Groupe Hospitalier Sud - Hôpital Haut-Lévêque
🇫🇷Bordeaux, France
Centre Oscar Lambret
🇫🇷Lille, France
ICO - Site René Gauducheau
🇫🇷Saint-Herblain, France
General Hospital of Athens Laiko
🇬🇷Athens, Greece
General Hospital of Athens of Chest Diseases "SOTIRIA"
🇬🇷Athens, Greece
Seoul National University Bundang Hospital, Department of Oncology Medical office
🇰🇷Gyeonggi-do, Korea, Republic of
General Hospital of Athens "Alexandra"
🇬🇷Athens, Greece
University General Hospital of Ioannina
🇬🇷Ioánnina, Greece
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
Ajou University Hospital, CRC room, Clinical Trial Center
🇰🇷Suwon, Korea, Republic of
Haga Ziekenhuis
🇳🇱Den Haag, Netherlands
VU Medisch Centrum
🇳🇱Amsterdam, Netherlands
Akershus University Hospital
🇳🇴Lørenskog, Norway
Philippine General Hospital, Clinical Trial Unit Room 5, Medical Research Laboratory
🇵🇭Ermita, Philippines
Radiumhospitalet, Montebello
🇳🇴Oslo, Norway
Cebu Doctors' University Hospital (CDUH), Research Office
🇵🇭Cebu City, Philippines
S.C Delta Health Care S.R.L
🇷🇴Bucuresti, Romania
Szpital Kliniczny im.Heliodora Swiecickiego Uniwersytetu Medycznego im.K. Marcinkowskiego w Poznaniu
🇵🇱Poznań, Poland
St. Luke's Medical Center, Human Cancer Biobank Research Center
🇵🇭Quezon City, Philippines
Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
🇵🇱Warszawa, Poland
MTZ Clinical Research
🇵🇱Warszawa, Poland
S.C Oncocenter Oncologie Clinica S.R.L.
🇷🇴Timişoara, Romania
TSBHI "Altai Territorial oncological dispensary"
🇷🇺Barnaul, Russian Federation
S.C Centrul de Oncologie Sf. Nectarie S.R.L.
🇷🇴Craiova, Romania
SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"
🇷🇺Arkhangel'sk, Russian Federation
LLC Evimed
🇷🇺Chelyabinsk, Russian Federation
FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
🇷🇺Moscow, Russian Federation
Tomsk Research Instutite of Oncology
🇷🇺Tomsk, Russian Federation
BHI of Omsk region "Clinical Oncology Dispensary"
🇷🇺Omsk, Russian Federation
Singapore National Cancer Center (SNCC)
🇸🇬Singapore, Singapore
Tan Tock Seng Hospital, Communicable Disease Centre
🇸🇬Singapore, Singapore
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Shuang Ho Hospital
🇨🇳New Taipei City, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Taichung Veterans General Hospital, The Radiation Oncology Department
🇨🇳Taichung, Taiwan
Taipei Medical University Hospital (TMUH)
🇨🇳Taipei, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital, Medical Science & Technology Building
🇨🇳Taipei, Taiwan
Linkou Chang-Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
SI V.T. Zaycev Institute of general & urgent surgery of National academy medical sciences of Ukraine, Department of purulent surgery
🇺🇦Kharkiv, Ukraine
Communal Non-profit Enterprise Regional Center of Oncology
🇺🇦Kharkiv, Ukraine
Ninewells Hospital
🇬🇧Dundee, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital (SNUH)
🇰🇷Seoul, Korea, Republic of
CTCA Cancer Treatment Centers
🇺🇸Tulsa, Oklahoma, United States
Guy's Hospital
🇬🇧London, United Kingdom