Tivozanib in Treating Patients With Liver Cancer That Is Metastatic or Cannot Be Removed by Surgery
|Advanced Adult Hepatocellular Carcinoma Non-Resectable Hepatocellular Carcinoma||Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Tivozanib||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Multicenter Phase 1b/2 Study of Tivozanib in Patients With Advanced Inoperable Hepatocellular Carcinoma|
- PFS, assessed using standard RECIST criteria [ Time Frame: 24 weeks ]Will be descriptively analyzed using standard Kaplan-Meier estimation along with the corresponding descriptive statistics and 95% confidence intervals.
- Clinical benefit rate (CR, PR, and SD) by RECIST [ Time Frame: Up to 3 years ]
- Incidence of adverse events and toxicities, assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4 [ Time Frame: Up to 3 years ]Toxicity frequency will be tabulated by grade across all dose levels and cycles for all patients in the safety sample and for the subset treated at the recommended phase 2 dose.
- OS [ Time Frame: Up to 3 years ]
- AFP response [ Time Frame: Up to 3 years ]
- Antiviral effects (if any in those with HBV or HCV associated HCC) [ Time Frame: Up to 3 years ]
- Drug exposure, as assessed by steady state PK [ Time Frame: Up to 3 years ]Associations between drug exposure and response/survival and toxicity by quartiles of drug exposure.
|Actual Study Start Date:||July 11, 2013|
|Estimated Study Completion Date:||August 14, 2018|
|Primary Completion Date:||May 16, 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (tivozanib)
Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
Correlative studiesDrug: Tivozanib
Other Name: AV-951
I. Progression free survival (PFS) at 24 weeks in patients with advanced hepatocellular carcinoma (HCC).
I. To determine the safety of tivozanib in HCC. II. To determine the overall survival (OS) and clinical benefit rate (complete response [CR], partial response [PR] and stable disease [SD]) by Response Evaluation Criteria in Solid Tumors (RECIST).
III. To determine the steady state pharmacokinetics (PK) and soluble vascular endothelial growth factor receptor 2 (VEGFR-2) baseline/change with tivozanib and use modeling to correlate exposure with biomarker change and the primary outcome measure of PFS.
IV. To determine the change in viral load (hepatitis B virus [HBV] and hepatitis C virus [HCV]) during therapy in patients with HBV or HCV associated HCC.
V. To determine the change in tumor marker (alfa fetoprotein) with tivozanib therapy is in the effect of tivozanib on several tumor-associated immune response markers.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive tivozanib orally (PO) once daily (QD) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01835223
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|United States, Ohio|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106|
|Principal Investigator:||Renuka Iyer||Roswell Park Cancer Institute|