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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02508467
Recruitment Status : Active, not recruiting
First Posted : July 27, 2015
Last Update Posted : August 15, 2022
Sponsor:
Information provided by (Responsible Party):
Blueprint Medicines Corporation

Tracking Information
First Submitted Date  ICMJE July 9, 2015
First Posted Date  ICMJE July 27, 2015
Last Update Posted Date August 15, 2022
Actual Study Start Date  ICMJE July 31, 2015
Actual Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
  • 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 ]
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 23, 2015)
  • Maximum tolerated dose (MTD) [ Time Frame: 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 BLU-554 [ 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 ]
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
  • Maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules [ 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) ]
    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 [ 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) ]
    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 [ Time Frame: Cycle 2 (Day 56) ]
  • Levels of FGF19 in blood and tumor samples [ Time Frame: Cycle 1 (Day 28) ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2015)
  • Maximum plasma concentration of BLU-554 [ 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) ]
    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 BLU-554 [ 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) ]
    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 [ Time Frame: Cycle 2 (Day 56) ]
  • Levels of cancer antigen (CA) 19-9 and FGF 19 in blood and tumor samples [ Time Frame: Cycle 1 (Day 28) ]
  • Preliminary evidence of BLU-554 antineoplastic activity [ Time Frame: End of treatment (at approximately 24 months or earlier if patient terminates from the study) and every three months post EOT ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study of Fisogatinib (BLU-554) in Patients With Hepatocellular Carcinoma
Official Title  ICMJE A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BLU-554 in Patients With Hepatocellular Carcinoma
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatocellular Carcinoma (HCC)
Intervention  ICMJE Drug: Fisogatinib (BLU-554)
Other Name: BLU-554
Study Arms  ICMJE Experimental: Fisogatinib (BLU-554)
Fisogatinib (BLU-554) capsules for oral administration.
Intervention: Drug: Fisogatinib (BLU-554)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 5, 2018)		 150
Original Estimated Enrollment  ICMJE
 (submitted: July 23, 2015)		 60
Estimated Study Completion Date  ICMJE December 31, 2022
Actual Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China,   France,   Germany,   Hong Kong,   Italy,   Korea, Republic of,   Singapore,   Spain,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02508467
Other Study ID Numbers  ICMJE BLU-554-1101
2015-001662-26 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Blueprint Medicines Corporation
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Blueprint Medicines Corporation
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Blueprint Medicines Corporation
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP