NCT02508467

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
146

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jul 2015

Longer than P75 for phase_1

Geographic Reach
12 countries

41 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 9, 2015

Completed
18 days until next milestone

First Posted

Study publicly available on registry

July 27, 2015

Completed
4 days until next milestone

Study Start

First participant enrolled

July 31, 2015

Completed
5.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2021

Completed
2.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2024

Completed
Last Updated

April 12, 2024

Status Verified

March 1, 2024

Enrollment Period

5.9 years

First QC Date

July 9, 2015

Last Update Submit

April 10, 2024

Conditions

Keywords

Liver cancerFGF19 gene amplificationFGF19 overexpressionFGF19 upregulationCyclin D1 (CCND1) gene amplificationCyclin D1 (CCND1) copy number gainBLU-554FGFR4Hepatocellular carcinomaLiver DiseaseLiver Neoplasms

Outcome Measures

Primary Outcomes (3)

  • 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 Outcomes (5)

  • 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)

  • 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)

  • Fibroblast growth factor 19 (FGF19) status in tumor tissue

    Cycle 2 (Day 56)

  • Levels of FGF19 in blood and tumor samples

    Cycle 1 (Day 28)

  • 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

Study Arms (1)

Fisogatinib (BLU-554)

EXPERIMENTAL

Fisogatinib (BLU-554) capsules for oral administration.

Drug: Fisogatinib (BLU-554)

Interventions

Also known as: BLU-554
Fisogatinib (BLU-554)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (41)

Inland Empire Liver Foundation

Rialto, California, 92377, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Ochsner Cancer Institute

New Orleans, Louisiana, 70121, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02144, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Zhejiang Cancer Hospital

Hangzhou, Gongshu District, 310022, China

Location

Nanfang Hospital

Guangzhou, Guangdong, 510445, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Hunan Cancer Hospital, Radioactive Interventional Department

Changsha, Hunan, 410013, China

Location

The Chinese People's Liberation Army 81 Hospital

Nanjing, Jiangsu, 210002, China

Location

Nantong Tumor Hospital

Nantong, Jiangsu, 226361, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130012, China

Location

Jilin University the First Affiliated Hospital

Changchun, Jilin, 130021, China

Location

Fudan University Zhongshan Hospital

Xuhui, Shanghai City, 200032, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Tianjin Medical University Cancer Institute & Hospital, Hepatobiliary Oncology Department

Tianjin, West Lake District, 300060, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Xuhui District, 200032, China

Location

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

Hospital Beaujon

Clichy, 92110, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Johannes Gutenberg University Mainz - University Medical Center

Mainz, Rhineland-Palatine, 55131, Germany

Location

University of Frankfurt

Frankfurt, 60590, Germany

Location

Prince of Wales Hospital

Hong Kong, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

IRCCS Foundation - National Institute of Tumors

Milan, 21033, Italy

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

National Cancer Center

Gyeonggi-do, 10408, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Vall d'Hebron Institute of Oncology

Barcelona, 08035, Spain

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

University of Liverpool - Clatterbridge Cancer Centre

Bebington, CH63 4JY, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Guy's Hospital

London, SE1 9RY, United Kingdom

Location

University College London

London, W1T 7HA, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, HepatocellularLiver NeoplasmsLiver Diseases

Interventions

fisogatinib

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System Diseases

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 9, 2015

First Posted

July 27, 2015

Study Start

July 31, 2015

Primary Completion

June 30, 2021

Study Completion

February 28, 2024

Last Updated

April 12, 2024

Record last verified: 2024-03

Locations