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

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ClinicalTrials.gov Identifier: NCT02508467
Recruitment Status : Recruiting
First Posted : July 27, 2015
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
Blueprint Medicines Corporation

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 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 or disease Intervention/treatment Phase
Hepatocellular Carcinoma (HCC) Drug: BLU-554 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : July 2015
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : August 2020

Arm Intervention/treatment
Experimental: BLU-554
BLU-554 capsules for oral administration.
Drug: BLU-554



Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 Measures :
  1. 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) ]
    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)

  2. 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) ]
    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

  3. Fibroblast growth factor 19 (FGF19) status in tumor tissue [ Time Frame: Cycle 2 (Day 56) ]
  4. Levels of FGF19 in blood and tumor samples [ Time Frame: Cycle 1 (Day 28) ]
  5. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02508467


Contacts
Contact: Blueprint Medicines 617-714-6707 studydirector@blueprintmedicines.com

  Show 26 Study Locations
Sponsors and Collaborators
Blueprint Medicines Corporation

Responsible Party: Blueprint Medicines Corporation
ClinicalTrials.gov Identifier: NCT02508467     History of Changes
Other Study ID Numbers: BLU-554-1101
2015-001662-26 ( EudraCT Number )
First Posted: July 27, 2015    Key Record Dates
Last Update Posted: October 3, 2018
Last Verified: October 2018

Keywords provided by Blueprint Medicines Corporation:
BLU-554
Liver cancer
FGF19 gene amplification
FGF19 overexpression
FGF19 upregulation
Cyclin D1 (CCND1) gene amplification
Cyclin D1 (CCND1) copy number gain
FGFR4
Hepatocellular carcinoma
Liver Disease
Liver Neoplasms

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases