Phase II Trial of Tivozanib in Advanced Hepatocellular Cancer

The purpose of this study is to learn about the effect of the investigational agent tivozanib on the control of the tumor growth in hepatocellular (liver) cancer. The investigators also plan to collect information on the likelihood to develop side effects while on this treatment. Tivozanib is an oral medication (pill) taken once a day. This medication is designed to stop the tumor from developing new blood vessels.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Cancer
• Intervention / Treatment: Drug: Tivozanib

Detailed Description

Angiogenesis is the formation of new blood vessels. Angiogenesis is driven by cytokines including vascular endothelial growth factor. Tivozanib is an oral medication that inhibits vascular endothelial growth factor preventing tumor from developing new blood vessels.

The purpose of this study is to evaluate the effects of tivozanib on hepatocellular (liver) cancer. Participants in the study take tivozanib daily at a dose of 1 mg for 1month. if doing well the dose would be increased to 1.5 mg per day. Patients are monitored for response using CT or MRI scans every 2months. In addition, patients will have blood draws to evaluate the effects of tivozanib on blood vessels.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University, Winship Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with measurable, histological diagnosis of hepatocellular carcinoma (HCC) and whose disease is not amenable to surgical or regional therapy.

2. Prior allowed therapy:

   • Surgery including hepatic resection

     1. Minimum of 4 weeks since any surgical procedure.
     2. Patients must have adequately recovered from surgery.

   • Regional therapy

     1. Includes transarterial chemoembolization (TACE), drug-eluting bead [DEB]-TACE, percutaneous ethanol injection, radiofrequency/cryo ablation, Yttrium-90 radioembolization.
     2. More than 2 weeks must have lapsed from therapy.
     3. There must be an indicator lesion outside the treated area or clear evidence of progression in the treated lesion, not amenable for further local therapies.
     4. Concomitant sorafenib with regional therapy is allowed as long as no evidence of progression on sorafenib.
   • Prior adjuvant sorafenib is allowed, if completed more than 6 months prior to disease recurrence.
3. Adequate hematological, liver and metabolic organ function.
4. Signed informed consent.

Exclusion Criteria:

1. Patients with mixed histology or fibrolamellar variant.
2. Prior systemic therapy for metastatic disease.
3. Uncontrolled hypertension (HTN).
4. Symptomatic heart failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tivozanib; Patients would receive Tivozanib 1.0 mg/day orally, 3 weeks on, one week off, for one cycle starting day 1. If no adverse event is encountered, patients will continue subsequent cycles of Tivozanib 1.5 mg/day orally; 3 weeks on/1 week off, dosing schedule. Patients will continue on treatment until disease progression, unacceptable toxicity, or patient withdrawal from the study.

Drug: Tivozanib; Oral medication given daily. No placebo.; Other Names: AV-951

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Advanced Hepatocellular Cancer (HCC) Receiving Tivozanib Who Are Free From Progression	Evaluation of disease progression in the patients with advanced hepatocellular cancer (HCC) receiving tivozanib will be made using CT or MRI scan of the organ(s) with the target lesion(s). Response Evaluation Criteria In Solid Tumors (RECIST) criteria 1.1 will be used for objective tumor response assessment. Measurable lesions can be measured in at least one dimension as ≥ 20 mm with conventional CT scan techniques or as ≥ 10 mm with spiral CT scan. Target lesions are all measurable lesions up to a maximum of 5 lesions. Target lesions are selected for their size and suitability for accurate repetitive measurements. The sum of the longest diameter of all target lesions will be calculated and reported as the baseline sum longest diameter (LD). This will be used as a reference to further quantify objective response.	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) Criteria	Measurable lesions: Lesions that can be measured in at least one dimension as ≥ 20 mm with conventional CT scan techniques or as ≥ 10 mm with spiral CT scan. Non-measurable lesions: All other lesions including small lesions (longest diameter < 20 mm with conventional techniques) and other non-measurable lesions including: pleural effusions, ascites, and disease documented by indirect evidence (e.g. biochemical abnormalities). Target lesions: All measurable lesions up to a maximum of 5 lesions. Target lesions are selected for their size and suitability for accurate repetitive measurements. The sum of the longest diameter of all target lesions will be calculated and reported as the baseline sum longest diameter (LD). This will be used as a reference to further quantify objective response. Non-target lesions: All other lesions are identified as non-target lesions and should be followed as present or absent.	6 months

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: AVEO Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: March 6, 2013
• First Submitted That Met QC Criteria: March 7, 2013
• First Posted (Estimate): March 8, 2013

Study Record Updates

• Last Update Posted (Estimate): April 22, 2016
• Last Update Submitted That Met QC Criteria: March 22, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Angiogenesis; Tivozanib; Advanced hepatocellular cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Carcinoma, Hepatocellular; Liver Neoplasms
• Other Study ID Numbers: IRB00061422 (Other Identifier: Emory University); WINSHIP2302-12 (Other Identifier: Other)