Clinical trial NCT02508467: A Phase 1 Study of Fisogatinib (BLU-554) in Patients With Hepatocellular Carcinoma
Official title: A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BLU-554 in Patients With Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatocellular Carcinoma (HCC)
Keywords: Liver cancer
FGF19 gene amplification
FGF19 overexpression
FGF19 upregulation
Cyclin D1 (CCND1) gene amplification
Cyclin D1 (CCND1) copy number gain
BLU-554
FGFR4
Hepatocellular carcinoma
Liver Disease
Liver Neoplasms
Lead sponsor: Blueprint Medicines Corporation
Sponsor class: INDUSTRY
First posted: 2015-07-27
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

* 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 Exclusion Criteria:

* 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

Primary outcomes:
measure: Maximum tolerated dose (MTD) on qd and bid schedules
timeFrame: During cycle 1 (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier
measure: Recommended Phase 2 dose of fisogatinib (BLU-554) on qd and bid schedules
timeFrame: 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
measure: Number of patients with adverse events, serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings
timeFrame: Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study
Secondary outcomes:
measure: Maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules
timeFrame: Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)
measure: Time to maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules
timeFrame: Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)
measure: Fibroblast growth factor 19 (FGF19) status in tumor tissue
timeFrame: Cycle 2 (Day 56)
measure: Levels of FGF19 in blood and tumor samples
timeFrame: Cycle 1 (Day 28)
measure: Preliminary evidence of fisogatinib (BLU-554) antineoplastic activity
timeFrame: 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
Other outcomes:
Locations:
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: Miami
country: United States
facility: University of Miami - Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: New Orleans
country: United States
facility: Ochsner Cancer Institute
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Gongshu District
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital, Radioactive Interventional Department
state: Hunan
city: Nanjing
country: China
facility: The Chinese People's Liberation Army 81 Hospital
state: Jiangsu
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: Jilin University the First Affiliated Hospital
state: Jilin
city: Xuhui
country: China
facility: Fudan University Zhongshan Hospital
state: Shanghai City
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital, Hepatobiliary Oncology Department
state: West Lake District
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Xuhui District
city: Hangzhou
country: China
facility: The First Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
city: Clichy
country: France
facility: Hospital Beaujon
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Mainz
country: Germany
facility: Johannes Gutenberg University Mainz - University Medical Center
state: Rhineland-Palatine
city: Frankfurt
country: Germany
facility: University of Frankfurt
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Milan
country: Italy
facility: IRCCS Foundation - National Institute of Tumors
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Bebington
country: United Kingdom
facility: University of Liverpool - Clatterbridge Cancer Centre
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: University College London
Study officials:
References: