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Trial record 1 of 1 for:    NCT01835223
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Tivozanib in Treating Patients With Liver Cancer That Is Metastatic or Cannot Be Removed by Surgery

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ClinicalTrials.gov Identifier: NCT01835223
Recruitment Status : Completed
First Posted : April 18, 2013
Results First Posted : October 28, 2020
Last Update Posted : October 28, 2020
Sponsor:
Collaborators:
National Comprehensive Cancer Network
AVEO Pharmaceuticals, Inc.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Tracking Information
First Submitted Date  ICMJE April 15, 2013
First Posted Date  ICMJE April 18, 2013
Results First Submitted Date  ICMJE June 5, 2020
Results First Posted Date  ICMJE October 28, 2020
Last Update Posted Date October 28, 2020
Actual Study Start Date  ICMJE July 11, 2013
Actual Primary Completion Date December 24, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2013)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2020)
  • Clinical Benefit Rate (CR, PR, and SD) by RECIST [ Time Frame: Up to 3 years ]
    The number of patients achieving clinical benefit (CR, PR, or SD by RECIST).
  • 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.
  • Overall Survival Rate [ Time Frame: Up to 3 years ]
    Overall survival is defined as the time from treatment until death or last follow-up.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2013)
  • OS [ Time Frame: Up to 3 years ]
  • Toxicities assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 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.
  • Clinical Benefit Rate (CR, PR, and SD) by RECIST [ Time Frame: Up to 3 years ]
Current Other Pre-specified Outcome Measures
 (submitted: October 6, 2020)
  • AFP Response [ Time Frame: Up to 3 years ]
    Defined as an AFP decrease greater than 50%.
  • 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tivozanib in Treating Patients With Liver Cancer That Is Metastatic or Cannot Be Removed by Surgery
Official Title  ICMJE Multicenter Phase 1b/2 Study of Tivozanib in Patients With Advanced Inoperable Hepatocellular Carcinoma
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Adult Hepatocellular Carcinoma
  • Non-Resectable Hepatocellular Carcinoma
Intervention  ICMJE
  • Drug: Tivozanib (1mg)
    Given PO
    Other Names:
    • AV-951
    • TIVOZANIB
  • Drug: Tivozanib (1.5mg)
    Given PO
    Other Names:
    • AV-951
    • TIVOZANIB
Study Arms  ICMJE
  • Experimental: 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.
    Intervention: Drug: Tivozanib (1mg)
  • Experimental: 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.
    Intervention: Drug: Tivozanib (1.5mg)
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 6, 2020)
33
Original Estimated Enrollment  ICMJE
 (submitted: April 15, 2013)
43
Actual Study Completion Date  ICMJE November 8, 2019
Actual Primary Completion Date December 24, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 (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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01835223
Other Study ID Numbers  ICMJE I 229112
NCI-2013-00756 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 229112 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE
  • National Comprehensive Cancer Network
  • AVEO Pharmaceuticals, Inc.
  • National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Renuka Iyer Roswell Park Cancer Institute
PRS Account Roswell Park Cancer Institute
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP