A Phase 1 Study of Fisogatinib (BLU-554) in Patients With Hepatocellular Carcinoma
- Registration Number
- NCT02508467
- Lead Sponsor
- Blueprint Medicines Corporation
- Brief Summary
This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of fisogatinib (formerly known as BLU- 554) administered orally in patients with FGF19 IHC+ hepatocellular carcinoma (HCC). The study consists of 3 parts, a dose-escalation part (Part 1), an expansion part (Part 2) exploring a once daily (qd) dosing schedule at the recommended Phase 2 dose (RP2D), and a Part 3 expansion of the qd dosing schedule at the RP2D in TKI naive patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 146
- Confirmed diagnosis of HCC by histological examination or by non-invasive criteria according to European Association for the Study of the Liver (EASL) or American Association for the Study of Liver Disease (AASLD) guidelines (Part 1, 2 and 3).
- For Part 1 and 2, the patient has unresectable disease and has been previously treated with sorafenib, has declined treatment with sorafenib, or does not have access to sorafenib.
- For Part 3, the patient has not received prior treatment with a TKI.
- Child-Pugh class A with no clinically apparent ascites
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- For Part 1, willing to provide archived tumor tissue (if available) and willing to undergo pre- and on-treatment tumor biopsy (if considered safe and medically feasible by the treating investigator)
- For Part 2 and 3, all patients must have an FGF19 IHC result available. Only FGF19 IHC+ HCC patients will be eligible for Part 3.
Key
- Central nervous system metastases
- Platelet count <75,000/mL
- Absolute neutrophil count <1000/mL
- Hemoglobin <8 g/dL
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x the upper limit of normal (ULN)
- Total bilirubin >2.5 mg/dL
- International normalized ratio (INR) >2.3 or prothrombin time (PT) >6 seconds above control
- Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Fisogatinib (BLU-554) Fisogatinib (BLU-554) Fisogatinib (BLU-554) capsules for oral administration.
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) on qd and bid schedules During cycle 1 (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier Recommended Phase 2 dose of fisogatinib (BLU-554) on qd and bid schedules At the end of every cycle (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier Number of patients with adverse events, serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study
- Secondary Outcome Measures
Name Time Method Fibroblast growth factor 19 (FGF19) status in tumor tissue Cycle 2 (Day 56) Maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study) Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and end of treatment (EOT)
Preliminary evidence of fisogatinib (BLU-554) antineoplastic activity Screening, Day 1 of every odd numbered cycle starting with Cycle 3, End of treatment (at approximately 24 months or earlier if patient terminates from the study) and every three months post EOT Time to maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study) Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and EOT
Levels of FGF19 in blood and tumor samples Cycle 1 (Day 28)
Trial Locations
- Locations (41)
Nantong Tumor Hospital
🇨🇳Nantong, Jiangsu, China
The Chinese People's Liberation Army 81 Hospital
🇨🇳Nanjing, Jiangsu, China
Tianjin Medical University Cancer Institute & Hospital, Hepatobiliary Oncology Department
🇨🇳Tianjin, West Lake District, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Xuhui District, China
Prince of Wales Hospital
🇭🇰Hong Kong, Hong Kong
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Cancer Center
🇰🇷Gyeonggi-do, Korea, Republic of
Jilin University the First Affiliated Hospital
🇨🇳Changchun, Jilin, China
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University of Miami - Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Ochsner Cancer Institute
🇺🇸New Orleans, Louisiana, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Gongshu District, China
Nanfang Hospital
🇨🇳Guangzhou, Guangdong, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Hunan Cancer Hospital, Radioactive Interventional Department
🇨🇳Changsha, Hunan, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
Fudan University Zhongshan Hospital
🇨🇳Xuhui, Shanghai City, China
Hospital Beaujon
🇫🇷Clichy, France
The First Affiliated Hospital, College of Medicine, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Institut Gustave Roussy
🇫🇷Villejuif, France
Johannes Gutenberg University Mainz - University Medical Center
🇩🇪Mainz, Rhineland-Palatine, Germany
University of Frankfurt
🇩🇪Frankfurt, Germany
IRCCS Foundation - National Institute of Tumors
🇮🇹Milan, Italy
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
National Cancer Centre
🇸🇬Singapore, Singapore
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Vall d'Hebron Institute of Oncology
🇪🇸Barcelona, Spain
Inselspital Bern
🇨🇭Bern, Switzerland
University of Liverpool - Clatterbridge Cancer Centre
🇬🇧Bebington, United Kingdom
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Royal Free Hospital
🇬🇧London, United Kingdom
University College London
🇬🇧London, United Kingdom
Guy's Hospital
🇬🇧London, United Kingdom