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Phase II Trial of Tivozanib in Advanced Hepatocellular Cancer

Primary Purpose

Hepatocellular Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tivozanib
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Cancer focused on measuring Tivozanib, Advanced hepatocellular cancer, Angiogenesis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Emory University, Winship Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tivozanib

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
March 6, 2013
Last Updated
March 22, 2016
Sponsor
Emory University
Collaborators
AVEO Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01807156
Brief Title
Phase II Trial of Tivozanib in Advanced Hepatocellular Cancer
Official Title
Phase II Trial of Tivozanib in Advanced Hepatocellular Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Terminated
Why Stopped
Primary endpoint not met
Study Start Date
March 2013 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
AVEO Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Cancer
Keywords
Tivozanib, Advanced hepatocellular cancer, Angiogenesis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tivozanib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tivozanib
Other Intervention Name(s)
AV-951
Intervention Description
Oral medication given daily. No placebo.
Primary Outcome Measure Information:
Title
Number of Patients With Advanced Hepatocellular Cancer (HCC) Receiving Tivozanib Who Are Free From Progression
Description
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.
Time Frame
6 Months
Secondary Outcome Measure Information:
Title
Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Description
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.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with measurable, histological diagnosis of hepatocellular carcinoma (HCC) and whose disease is not amenable to surgical or regional therapy. Prior allowed therapy: Surgery including hepatic resection Minimum of 4 weeks since any surgical procedure. Patients must have adequately recovered from surgery. Regional therapy Includes transarterial chemoembolization (TACE), drug-eluting bead [DEB]-TACE, percutaneous ethanol injection, radiofrequency/cryo ablation, Yttrium-90 radioembolization. More than 2 weeks must have lapsed from therapy. 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. 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. Adequate hematological, liver and metabolic organ function. Signed informed consent. Exclusion Criteria: Patients with mixed histology or fibrolamellar variant. Prior systemic therapy for metastatic disease. Uncontrolled hypertension (HTN). Symptomatic heart failure.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bassel El-Rayes, MD
Organizational Affiliation
Emory University Winship Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University, Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Phase II Trial of Tivozanib in Advanced Hepatocellular Cancer

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