HumRes25861
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SNCTP000002747
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BASEC2017-00275
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NCT02508467
A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics as well as to Collect Preliminary Efficacy Data of BLU-554 in Patients with Hepatocellular Carcinoma
Summary description of the study
This study is designed to obtain information about the safety and tolerability of the study drug BLU-554 when administered to patients with hepatocellular carcinoma (HCC), i.e., liver cancer. Since this is a study drug, this means that it is not yet known whether this drug helps patients and it is not commercially available. This study drug has not yet been tested in humans. This 3-part study includes a phase in which the most effective dose of the study drug with the fewest side effects is to be found, as well as two additional phases in which the safety and good tolerability of the chosen dose are to be confirmed.
(BASEC)
Intervention under investigation
We are conducting this study to determine the highest tolerable dose of the study drug and to prove (in phases 2 and 3) that this dose is safe and well tolerated.
(BASEC)
Disease under investigation
Hepatocellular Carcinoma / Liver Cancer
(BASEC)
Criteria for participation in trial
For Parts 1 and 2: Patients with a confirmed diagnosis of hepatocellular carcinoma (HCC) based on the examination of tissue samples or other criteria. Patients with an unresectable carcinoma who have previously been treated with sorafenib, have declined sorafenib, or have had no access to sorafenib. For Parts 2 and 3: Patients with at least one tissue lesion that can be evaluated according to certain criteria for assessing treatment response in solid tumors. (BASEC)
Exclusion criteria
known metastases of the central nervous system (CNS) suspected CNS metastases family history of prolonged QT syndrome clinically significant, uncontrolled cardiovascular diseases including congestive heart failure grade III or IV; myocardial infarction or unstable myocarditis within the previous 6 months, uncontrolled hypertension or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (e.g., second-degree type II heart block or third-degree heart block) (BASEC)
For Parts 1 and 2: Patients with a confirmed diagnosis of hepatocellular carcinoma (HCC) based on the examination of tissue samples or other criteria. Patients with an unresectable carcinoma who have previously been treated with sorafenib, have declined sorafenib, or have had no access to sorafenib. For Parts 2 and 3: Patients with at least one tissue lesion that can be evaluated according to certain criteria for assessing treatment response in solid tumors. (BASEC)
Exclusion criteria
known metastases of the central nervous system (CNS) suspected CNS metastases family history of prolonged QT syndrome clinically significant, uncontrolled cardiovascular diseases including congestive heart failure grade III or IV; myocardial infarction or unstable myocarditis within the previous 6 months, uncontrolled hypertension or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (e.g., second-degree type II heart block or third-degree heart block) (BASEC)
Trial sites
Bern
(BASEC)
China, France, Germany, Hong Kong, Italy, Korea, Republic of, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States (ICTRP)
Sponsor
not available
Contact
Contact Person Switzerland
Prof. Dr. Jean Francois Dufour
+41 31 632 8026
jean-francois.dufour@clutterinsel.ch(BASEC)
Scientific Information
not available
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Bern
(BASEC)
Date of authorisation
05.01.2018
(BASEC)
ICTRP Trial ID
NCT02508467 (ICTRP)
Official title (approved by ethics committee)
not available
Academic title
A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BLU-554 in Patients With Hepatocellular Carcinoma (ICTRP)
Public title
A Phase 1 Study of Fisogatinib (BLU-554) in Patients With Hepatocellular Carcinoma (ICTRP)
Disease under investigation
Hepatocellular Carcinoma (HCC) (ICTRP)
Intervention under investigation
Drug: Fisogatinib (BLU-554) (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Inclusion/Exclusion criteria
Gender: All
Maximum age: N/A
Minimum age: 18 Years
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
(ICTRP)
not available
Primary and secondary end points
Maximum tolerated dose (MTD) on qd and bid schedules;Recommended Phase 2 dose of fisogatinib (BLU-554) on qd and bid schedules;Number of patients with adverse events, serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings (ICTRP)
Maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules;Time to maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules;Fibroblast growth factor 19 (FGF19) status in tumor tissue;Levels of FGF19 in blood and tumor samples;Preliminary evidence of fisogatinib (BLU-554) antineoplastic activity (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
not available
Secondary trial IDs
2015-001662-26, BLU-554-1101 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT02508467 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available