A Phase 1 Study of Fisogatinib (BLU-554) in Patients With Hepatocellular Carcinoma
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| ClinicalTrials.gov Identifier: NCT02508467 |
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Recruitment Status :
Active, not recruiting
First Posted : July 27, 2015
Last Update Posted : February 3, 2021
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Sponsor:
Blueprint Medicines Corporation
Information provided by (Responsible Party):
Blueprint Medicines Corporation
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hepatocellular Carcinoma (HCC) | Drug: Fisogatinib (BLU-554) | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 150 participants |
| Allocation: | N/A |
| 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 2021 |
| Estimated Study Completion Date : | April 2021 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Fisogatinib (BLU-554)
Fisogatinib (BLU-554) capsules for oral administration.
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Drug: Fisogatinib (BLU-554)
Other Name: BLU-554 |
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 ]
- 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 ]
Secondary Outcome Measures :
- 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 ]
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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
Locations
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Sponsors and Collaborators
Blueprint Medicines Corporation
| Responsible Party: | Blueprint Medicines Corporation |
| ClinicalTrials.gov Identifier: | NCT02508467 |
| Other Study ID Numbers: |
BLU-554-1101 2015-001662-26 ( EudraCT Number ) |
| First Posted: | July 27, 2015 Key Record Dates |
| Last Update Posted: | February 3, 2021 |
| Last Verified: | February 2021 |
Keywords provided by Blueprint Medicines Corporation:
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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:
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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 |