Phase II Trial of Tivozanib in Advanced Hepatocellular Cancer
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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 Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- Number of Patients With Advanced Hepatocellular Cancer (HCC) Receiving Tivozanib Who Are Free From Progression [6 Months]
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 [6 months]
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.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Emory University, Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
Sponsors and Collaborators
- Emory University
- AVEO Pharmaceuticals, Inc.
Investigators
- Principal Investigator: Bassel El-Rayes, MD, Emory University Winship Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB00061422
- IRB00061422
- WINSHIP2302-12
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Tivozanib |
|---|---|
| Arm/Group 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. Tivozanib: Oral medication given daily. No placebo. |
| Period Title: Overall Study | |
| STARTED | 7 |
| COMPLETED | 6 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Tivozanib |
|---|---|
| Arm/Group 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. Tivozanib: Oral medication given daily. No placebo. |
| Overall Participants | 7 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
55
|
| Sex: Female, Male (Count of Participants) | |
| Female |
2
28.6%
|
| Male |
5
71.4%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
1
14.3%
|
| White |
6
85.7%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
7
100%
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tivozanib |
|---|---|
| Arm/Group 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. Tivozanib: Oral medication given daily. No placebo. |
| Measure Participants | 6 |
| Number [participants] |
1
14.3%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| No response was observed in any of the patients. |
| Arm/Group Title | Tivozanib |
|---|---|
| Arm/Group 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. Tivozanib: Oral medication given daily. No placebo. |
| Measure Participants | 6 |
| Number [participants] |
0
0%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Tivozanib | |
| Arm/Group 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. Tivozanib: Oral medication given daily. No placebo. | |
All Cause Mortality |
||
| Tivozanib | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Tivozanib | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/7 (14.3%) | |
| Cardiac disorders | ||
| Pulmonary Embolism | 1/7 (14.3%) | |
Other (Not Including Serious) Adverse Events |
||
| Tivozanib | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/7 (71.4%) | |
| Blood and lymphatic system disorders | ||
| Hyperglycemia | 2/7 (28.6%) | |
| Cardiac disorders | ||
| Hypertension | 3/7 (42.9%) | |
| General disorders | ||
| Nausea | 1/7 (14.3%) | |
| Fatigue | 1/7 (14.3%) | |
| Insomnia | 2/7 (28.6%) | |
| Abdominal Pain | 1/7 (14.3%) | |
| Hepatobiliary disorders | ||
| Liver Function Test Elevation | 1/7 (14.3%) | |
| Nervous system disorders | ||
| Headache | 1/7 (14.3%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Bassel El-Rayes, MD |
|---|---|
| Organization | Emory University |
| Phone | 404-778-1900 |
| bassel.el-rayes@emoryhealthcare.org |
- IRB00061422
- IRB00061422
- WINSHIP2302-12