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A Phase 1 Study of Fisogatinib (BLU-554) in Patients With Hepatocellular Carcinoma

Primary Purpose

Hepatocellular Carcinoma (HCC)

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Fisogatinib (BLU-554)
Sponsored by
Blueprint Medicines Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma (HCC) focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Inland Empire Liver Foundation
  • University of Miami - Sylvester Comprehensive Cancer Center
  • H. Lee Moffitt Cancer Center
  • Ochsner Cancer Institute
  • Massachusetts General Hospital
  • Mount Sinai Medical Center
  • Huntsman Cancer Institute
  • Zhejiang Cancer Hospital
  • Nanfang Hospital
  • Harbin Medical University Cancer Hospital
  • Henan Cancer Hospital
  • Hunan Cancer Hospital, Radioactive Interventional Department
  • The Chinese People's Liberation Army 81 Hospital
  • Nantong Tumor Hospital
  • Jilin Cancer Hospital
  • Jilin University the First Affiliated Hospital
  • Fudan University Zhongshan Hospital
  • West China Hospital, Sichuan University
  • Tianjin Medical University Cancer Institute & Hospital, Hepatobiliary Oncology Department
  • Fudan University Shanghai Cancer Center
  • The First Affiliated Hospital, College of Medicine, Zhejiang University
  • Hospital Beaujon
  • Institut Gustave Roussy
  • Johannes Gutenberg University Mainz - University Medical Center
  • University of Frankfurt
  • Prince of Wales Hospital
  • Queen Mary Hospital
  • IRCCS Foundation - National Institute of Tumors
  • National Cancer Center
  • Seoul National University Hospital
  • Asan Medical Center
  • Samsung Medical Center
  • National Cancer Centre
  • Vall d'Hebron Institute of Oncology
  • Inselspital Bern
  • National Cheng Kung University Hospital
  • National Taiwan University Hospital
  • University of Liverpool - Clatterbridge Cancer Centre
  • Royal Free Hospital
  • Guy's Hospital
  • University College London

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fisogatinib (BLU-554)

Arm Description

Fisogatinib (BLU-554) capsules for oral administration.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) on qd and bid schedules
Recommended Phase 2 dose of fisogatinib (BLU-554) on qd and bid schedules
Number of patients with adverse events, serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings

Secondary Outcome Measures

Maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules
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)
Time to maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules
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
Fibroblast growth factor 19 (FGF19) status in tumor tissue
Levels of FGF19 in blood and tumor samples
Preliminary evidence of fisogatinib (BLU-554) antineoplastic activity

Full Information

First Posted
July 9, 2015
Last Updated
February 7, 2023
Sponsor
Blueprint Medicines Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT02508467
Brief Title
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

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 31, 2015 (Actual)
Primary Completion Date
June 30, 2021 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Blueprint Medicines Corporation

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fisogatinib (BLU-554)
Arm Type
Experimental
Arm Description
Fisogatinib (BLU-554) capsules for oral administration.
Intervention Type
Drug
Intervention Name(s)
Fisogatinib (BLU-554)
Other Intervention Name(s)
BLU-554
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) on qd and bid schedules
Time Frame
During cycle 1 (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier
Title
Recommended Phase 2 dose of fisogatinib (BLU-554) on qd and bid schedules
Time Frame
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
Title
Number of patients with adverse events, serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings
Time Frame
Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study
Secondary Outcome Measure Information:
Title
Maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules
Description
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)
Time Frame
Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)
Title
Time to maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules
Description
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
Time Frame
Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)
Title
Fibroblast growth factor 19 (FGF19) status in tumor tissue
Time Frame
Cycle 2 (Day 56)
Title
Levels of FGF19 in blood and tumor samples
Time Frame
Cycle 1 (Day 28)
Title
Preliminary evidence of fisogatinib (BLU-554) antineoplastic activity
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Inland Empire Liver Foundation
City
Rialto
State/Province
California
ZIP/Postal Code
92377
Country
United States
Facility Name
University of Miami - Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
H. Lee Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Ochsner Cancer Institute
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02144
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Gongshu District
ZIP/Postal Code
310022
Country
China
Facility Name
Nanfang Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510445
Country
China
Facility Name
Harbin Medical University Cancer Hospital
City
Harbin
State/Province
Heilongjiang
ZIP/Postal Code
150081
Country
China
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450008
Country
China
Facility Name
Hunan Cancer Hospital, Radioactive Interventional Department
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Facility Name
The Chinese People's Liberation Army 81 Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210002
Country
China
Facility Name
Nantong Tumor Hospital
City
Nantong
State/Province
Jiangsu
ZIP/Postal Code
226361
Country
China
Facility Name
Jilin Cancer Hospital
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130012
Country
China
Facility Name
Jilin University the First Affiliated Hospital
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Facility Name
Fudan University Zhongshan Hospital
City
Xuhui
State/Province
Shanghai City
ZIP/Postal Code
200032
Country
China
Facility Name
West China Hospital, Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Tianjin Medical University Cancer Institute & Hospital, Hepatobiliary Oncology Department
City
Tianjin
State/Province
West Lake District
ZIP/Postal Code
300060
Country
China
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Xuhui District
ZIP/Postal Code
200032
Country
China
Facility Name
The First Affiliated Hospital, College of Medicine, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Facility Name
Hospital Beaujon
City
Clichy
ZIP/Postal Code
92110
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Johannes Gutenberg University Mainz - University Medical Center
City
Mainz
State/Province
Rhineland-Palatine
ZIP/Postal Code
55131
Country
Germany
Facility Name
University of Frankfurt
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Prince of Wales Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
IRCCS Foundation - National Institute of Tumors
City
Milan
ZIP/Postal Code
21033
Country
Italy
Facility Name
National Cancer Center
City
Gyeonggi-do
ZIP/Postal Code
10408
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
National Cancer Centre
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
Vall d'Hebron Institute of Oncology
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Inselspital Bern
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
National Cheng Kung University Hospital
City
Tainan
ZIP/Postal Code
704
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
Facility Name
University of Liverpool - Clatterbridge Cancer Centre
City
Bebington
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
Facility Name
Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Guy's Hospital
City
London
ZIP/Postal Code
SE1 9RY
Country
United Kingdom
Facility Name
University College London
City
London
ZIP/Postal Code
W1T 7HA
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A Phase 1 Study of Fisogatinib (BLU-554) in Patients With Hepatocellular Carcinoma

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