Tivozanib in Treating Patients With Liver Cancer That is Metastatic or Cannot Be Removed by Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Roswell Park Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01835223
First received: April 15, 2013
Last updated: October 2, 2014
Last verified: October 2014
  Purpose

This phase I/II trial studies the side effects and best dose of tivozanib and to see how well it works in treating patients with liver cancer that has spread to other parts of the body or cannot be removed by surgery. Tivozanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
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)
Drug: tivozanib
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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.


Estimated Enrollment: 49
Study Start Date: July 2013
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: tivozanib
Given PO
Other Names:
  • AV-951
  • oral VEGF receptor tyrosine kinase inhibitor AV-951
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Advanced staged HCC (unresectable and not amenable to local or regional therapy; or metastatic HCC); the diagnosis of HCC should be based on at least one of the following:

    • 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
  • 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 prior anti-angiogenic therapy, including but not limited to sorafenib, brivanib, bevacizumab, or sunitinib
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01835223

Locations
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         
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
Principal Investigator: Renuka Iyer Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01835223     History of Changes
Other Study ID Numbers: I 229112, NCI-2013-00756, I 229112, P30CA016056
Study First Received: April 15, 2013
Last Updated: October 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on October 30, 2014