Tivozanib in Treating Patients With Liver Cancer That is Metastatic or Cannot Be Removed by Surgery
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Stage C Adult Primary Liver Cancer (BCLC)
Stage D Adult Primary Liver Cancer (BCLC)
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: No ]Will be descriptively analyzed using standard Kaplan-Meier estimation along with the corresponding descriptive statistics and 95% confidence intervals.
- OS [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: Yes ]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.
- Clinical benefit rate (CR, PR, and SD) by RECIST [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- AFP response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Antiviral effects (if any in those with HBV or HCV associated HCC) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Drug exposure, as assessed by steady state PK [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Associations between drug exposure and response/survival and toxicity by quartiles of drug exposure.
|Study Start Date:||July 2013|
|Estimated Primary Completion Date:||March 2016 (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 Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
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||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Roswell Park 877-275-7724 ASKRPCI@RoswellPark.org|
|Principal Investigator: Renuka V. Iyer|
|United States, Ohio|
|University Hospitals Case Medical Center||Recruiting|
|Cleveland, Ohio, United States, 44106|
|Contact: Smitha Krishnamurthi, MD 216-844-1006 email@example.com|
|Principal Investigator:||Renuka Iyer||Roswell Park Cancer Institute|