Clinical Trial - NCT02508467

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

Recruiting

Sponsor: Blueprint Medicines Corporation

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02508467

Protocol Info

Short Description: A Phase 1 Study of BLU-554 in Patients with Hepatocellular Carcinoma
Long Description: A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BLU-554 in Patients with Hepatocellular Carcinoma
MGH Status: Open
Sponsor: Blueprint Medicines
Disease Program: GI

Next Steps


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Purpose

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 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.
Condition Title Intervention Phase
Hepatocellular Carcinoma (HCC) BLU-554 Phase 1
Study Type Interventional
Official Title A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BLU-554 in Patients With Hepatocellular Carcinoma

Primary Outcome Measures

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] [Designated as safety issue: ]

Recommended Phase 2 dose of 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] [Designated as safety issue: ]

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] [Designated as safety issue: ]


Secondary Outcome Measures

Maximum plasma concentration of 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)] [Designated as safety issue: ]

Time to maximum plasma concentration of 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)] [Designated as safety issue: ]

Fibroblast growth factor 19 (FGF19) status in tumor tissue [Time Frame: Cycle 2 (Day 56)] [Designated as safety issue: ]

Levels of FGF19 in blood and tumor samples [Time Frame: Cycle 1 (Day 28)] [Designated as safety issue: ]

Preliminary evidence of 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] [Designated as safety issue: ]

Estimated Enrollment: 150
Study Start Date: July 2015
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: October 2020
Arms Assigned Interventions

Experimental:BLU-554

BLU-554 capsules for oral administration.
Drug:BLU-554

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02508467

Locations

  • United States, California
    • Inland Empire Liver Foundation Rialto, California, United States, 92377
  • United States, Florida
    • University of Miami - Sylvester Comprehensive Cancer Center Miami, Florida, United States, 33136
    • H. Lee Moffitt Cancer Center Tampa, Florida, United States, 33612
  • United States, Louisiana
    • Ochsner Cancer Institute New Orleans, Louisiana, United States, 70121
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02144
  • United States, New York
    • Mount Sinai Medical Center New York, New York, United States, 10029
  • United States, Utah
    • Huntsman Cancer Institute Salt Lake City, Utah, United States, 84112
  • China, Jiangsu
    • The Chinese People's Liberation Army 81 Hospital Nanjing, Jiangsu, China, 210002
  • France,
    • Hospital Beaujon Clichy, , France, 92110
    • Institut Gustave Roussy Villejuif, , France, 94805
  • Germany, Rhineland-Palatine
    • Johannes Gutenberg University Mainz - University Medical Center Mainz, Rhineland-Palatine, Germany, 55131
  • Germany,
    • University of Frankfurt Frankfurt, , Germany, 60590
  • Hong Kong,
    • Prince of Wales Hospital Hong Kong, , Hong Kong,
    • Queen Mary Hospital Hong Kong, , Hong Kong,
  • Italy,
    • IRCCS Foundation - National Institute of Tumors Milan, , Italy, 21033
  • Korea, Republic of,
    • National Cancer Center Gyeonggi-do, , Korea, Republic of, 10408
    • Seoul National University Hospital Seoul, , Korea, Republic of, 03080
    • Asan Medical Center Seoul, , Korea, Republic of, 05505
    • Samsung Medical Center Seoul, , Korea, Republic of, 06351
  • Singapore,
    • National Cancer Centre Singapore, , Singapore, 169610
  • Spain,
    • Vall d'Hebron Institute of Oncology Barcelona, , Spain, 08035
  • Switzerland,
    • Inselspital Bern Bern, , Switzerland, 3010
  • Taiwan,
    • National Cheng Kung University Hospital Tainan, , Taiwan, 704
    • National Taiwan University Hospital Taipei, , Taiwan, 100
  • United Kingdom,
    • University of Liverpool - Clatterbridge Cancer Centre Bebington, , United Kingdom, CH63 4JY
    • Royal Free Hospital London, , United Kingdom, NW3 2QG
    • Guy's Hospital London, , United Kingdom, SE1 9RY
    • University College London London, , United Kingdom, W1T 7HA

Sponsors and Collaborators

Blueprint Medicines Corporation

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02508467
Other Study ID Numbers: 2015-001662-26
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Blueprint Medicines Corporation:

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

Additional relevant MeSH terms:

Carcinoma

Carcinoma, Hepatocellular

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019