Tivozanib in Treating Patients With Liver Cancer That Is Metastatic or Cannot Be Removed by Surgery
NCT ID: NCT01835223
Last Updated: 2020-10-28
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
33 participants
INTERVENTIONAL
2013-07-11
2019-11-08
Brief Summary
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Detailed Description
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I. Progression free survival (PFS) at 24 weeks in patients with advanced hepatocellular carcinoma (HCC).
SECONDARY OBJECTIVES:
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.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Treatment (tivozanib - 1 mg)
Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Tivozanib (1mg)
Given PO
Treatment (tivozanib - 1.5 mg)
Patients receive tivozanib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Tivozanib (1.5mg)
Given PO
Interventions
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Tivozanib (1mg)
Given PO
Tivozanib (1.5mg)
Given PO
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Magnetic resonance imaging (MRI) or computed tomography (CT) consistent with liver cirrhosis AND at least one solid liver lesion measuring \>= 2 cm, with characteristics arterial enhancement and venous washout regardless of alpha-fetoprotein (AFP) levels
* AFP \>= 400 ng/mL AND evidence of at least one solid liver lesion \>= 2 cm regardless of specific imaging characteristics on CT or MRI
* Histological/cytology biopsy confirming HCC
* Patients must have measurable disease per RECIST 1.1 criteria defined as at least one lesion that can be accurately measured in at least one dimension, and that has not been the target of local or regional therapy including transarterial chemoembolization, intra-arterial chemotherapy, ethanol or radiofrequency ablation
* Life expectancy of greater than 3 months
* Child-Pugh liver function class A
* Aspartate aminotransferase (AST) =\< 5 x institutional upper limits of normal (ULN)
* Total bilirubin =\< 3 mg/dL
* International normalized ratio (INR) =\< 2.0 (unless due to therapeutic warfarin use)
* Serum albumin \> 2.8 g/dL
* Creatinine =\< 1.5 x institutional ULN
* Absolute neutrophil count (ANC) \>= 1200/mm\^3
* Platelets \>= 60,000/mm\^3
* Hemoglobin (Hgb) \>= 8.5 g/dL
* Patients must not have any evidence of bleeding diathesis or active gastrointestinal bleeding
* Patients must not be known to be human immunodeficiency virus (HIV) positive
* Patients must not have other uncontrolled intercurrent illnesses (excluding HBV or HCV); this includes (but is not limited to) ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Sexually active fertile patients (male and female), and their partners, must agree to use medically accepted methods of contraception during the course of the study and for 3 months after the last dose of the study drug
* Female patients of childbearing potential must have a negative pregnancy test at screening
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
* Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
Exclusion Criteria
* Patients who have had any prior line of systemic therapy including cytotoxic agents or molecularly targeted agents for advanced/unresectable disease; any number of prior regional therapies with transarterial chemoembolization (TACE), brachytherapy with yttrium-90 microsphere, intra-arterial chemotherapy, surgery, or ablative therapy are allowed
* Prior liver transplantation and on immunosuppression
* Known symptomatic or uncontrolled brain metastases or epidural disease
* Patient has a corrected QT interval (QTcF) \> 500 ms at screening
* The patient is unable to swallow pills or diagnosed with a gastrointestinal disorder that are likely to interfere with the absorption of the study drug or with the patient's ability to take regular oral medication
* The patient is pregnant or breastfeeding
* Patients with second primary cancer (except adequately treated nonmelanoma skin cancer, curatively treated in-situ carcinoma of the cervix or superficial bladder cancer, or other solid tumors including lymphoma without bone marrow involvement curatively treated with no evidence of disease for \>= 5 years)
* The patient has a previously-identified allergy or hypersensitivity to components of the study treatment formulation
* Patients receiving any medications or substances that are strong inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible; moderate inducers of CYP3A4 should be used with caution
* Urine protein: creatinine ratio \> 1
18 Years
ALL
No
Sponsors
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National Comprehensive Cancer Network
NETWORK
AVEO Pharmaceuticals, Inc.
INDUSTRY
National Cancer Institute (NCI)
NIH
Roswell Park Cancer Institute
OTHER
Responsible Party
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Principal Investigators
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Renuka Iyer
Role: PRINCIPAL_INVESTIGATOR
Roswell Park Cancer Institute
Locations
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Roswell Park Cancer Institute
Buffalo, New York, United States
Case Western Reserve University
Cleveland, Ohio, United States
Countries
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References
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Kalathil SG, Thanavala Y. Natural Killer Cells and T Cells in Hepatocellular Carcinoma and Viral Hepatitis: Current Status and Perspectives for Future Immunotherapeutic Approaches. Cells. 2021 May 28;10(6):1332. doi: 10.3390/cells10061332.
Kalathil SG, Thanavala Y. Importance of myeloid derived suppressor cells in cancer from a biomarker perspective. Cell Immunol. 2021 Mar;361:104280. doi: 10.1016/j.cellimm.2020.104280. Epub 2020 Dec 31.
Kalathil SG, Wang K, Hutson A, Iyer R, Thanavala Y. Tivozanib mediated inhibition of c-Kit/SCF signaling on Tregs and MDSCs and reversal of tumor induced immune suppression correlates with survival of HCC patients. Oncoimmunology. 2020 Sep 30;9(1):1824863. doi: 10.1080/2162402X.2020.1824863.
Fountzilas C, Gupta M, Lee S, Krishnamurthi S, Estfan B, Wang K, Attwood K, Wilton J, Bies R, Bshara W, Iyer R. A multicentre phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma. Br J Cancer. 2020 Mar;122(7):963-970. doi: 10.1038/s41416-020-0737-6. Epub 2020 Feb 10.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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NCI-2013-00756
Identifier Type: REGISTRY
Identifier Source: secondary_id
I 229112
Identifier Type: OTHER
Identifier Source: secondary_id
I 229112
Identifier Type: -
Identifier Source: org_study_id