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Study of Bavituximab and Sorafenib In Patients With Advanced Liver Cancer

Primary Purpose

Hepatocellular Carcinoma, Liver Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

bavituximab (0.3 mg/kg) and sorafenib

bavituximab (1.0 mg/kg ) and sorafenib

bavituximab (3.0 mg/kg) and sorafenib

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Cirrhosis, GI Cancer, Hepatitis, Oncology

Eligibility Criteria

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

Inclusion Criteria:

Patients must have a diagnosis of hepatocellular carcinoma by at least one criterion listed below:
- Histologically confirmed.
- MRI or CT consistent with liver cirrhosis and at least one solid liver lesion >2 cm with early enhancement and delayed enhancement washout regardless of AFP.
- AFP >400 ng/ml and evidence of at least one solid liver lesion >2 cm regardless of specific imaging characteristics on CT or MRI.
Locally advanced or metastatic disease.
Patients with locally advanced disease must have disease deemed to be unresectable or not eligible for hepatic transplantation. Determination will occur in the weekly GI DMT meeting by surgical oncologists and transplant surgeons.
Measurable disease, as defined as lesions that can accurately be measured in at least one dimension (longest diameter to be measured) according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at least 2 cm with conventional techniques or at least 1 cm with spiral computed tomography.
Child-Pugh Score A.
Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
Absolute neutrophil count ≥ 1,500 cells/mm3.
Platelet count ≥ 75,000 cells/mm3.
Total bilirubin ≤ 3.0 mg/dl.
Hemoglobin ≥ 8.5 g/dl.
AST and ALT ≤ 5.0 times upper limit of normal.
D-dimer ≤ 3 times upper limit of normal.
INR ≤ 1.8 (therapeutic anticoagulation allowed as long as medically indicated.

Exclusion Criteria:

History of bleeding diathesis or coagulopathy.
Symptomatic or clinically active brain metastases.
Major surgery within previous 4 weeks.
History of thromboembolic events (including both pulmonary embolisms and deep vein thrombosis); central venous catheter-related thrombosis > 6 months prior is allowed.
Prior adjuvant therapy with sorafenib or other Raf/MEK/RAS or VEGFR inhibitors. Prior adjuvant therapy is allowed provided it was completed > 6 months ago and there is documented recurrence of hepatocellular carcinoma.

Sites / Locations

UT Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily

Bavituximab: 1.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Bavituximab: 3.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Arm Description

Cohort 1: Participants were administered Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily

Cohort 2: Participants were administered Bavituximab:1.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Cohort 3: Participants were administered Bavituximab:3.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Outcomes

Primary Outcome Measures

Median Radiographic Time to Progression (TTP) Calculated From Treatment Initiation to First Evidence of Disease Progression or Last Follow-up.

Median radiographic time to progression (TTP) was calculated from treatment initiation to first evidence of disease progression or last follow-up by using the Kaplan-Meier method. The 95% confidence intervals (CIs) for time-to-progression data was calculated using Greenwood's formula.

Number of Patients With Dose Limiting Toxicity

Dose limiting toxicity by serious adverse events by CTCAE version 4.0

Secondary Outcome Measures

Safety, as Measured by the Number of Patients With Adverse Event Related to the Treatment That Experienced Grade 3 or Greater.

Safety was measured by the number of patients with at least one adverse event as assess by NCI Common Terminology criteria for adverse events (CTCAE)

Median Months of Overall Survival Calculated From Treatment Initiation to Death or Last Follow-up.

Median months of overall survival was calculated from treatment initiation to death or last follow-up by using the Kaplan-Meier method. The 95% confidence intervals (CIs) for median months of overall survival was calculated using Greenwood's formula.

Median Months of Disease Specific Survival Calculated From Treatment Initiation to Death From Advanced HCC (Hepatocellular Carcinoma) or Last Follow-up.

Median months of disease specific survival was calculated from treatment initiation to first evidence of death from advanced liver cancer or last follow-up by using the Kaplan-Meier method. The 95% confidence intervals (CIs) for time-to-disease specific survival data was calculated using Greenwood's formula.

Full Information

NCT ID

NCT01264705

First Posted

December 1, 2010

Last Updated

October 22, 2020

Sponsor

University of Texas Southwestern Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01264705

Brief Title

Study of Bavituximab and Sorafenib In Patients With Advanced Liver Cancer

Official Title

A Phase I/II Study of Bavituximab and Sorafenib In Patients With Advanced Hepatocellular Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

January 2011 (undefined)

Primary Completion Date

April 2018 (Actual)

Study Completion Date

April 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Texas Southwestern Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a non-randomized, open-label, single-institution phase I/II therapeutic trial of bavituximab and sorafenib in patients with advanced hepatocellular carcinoma (HCC). This study will be activated at the UT Southwestern Medical Center, comprised of The Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Hospitals-St. Paul and Parkland Memorial Hospital System. Advanced HCC is defined as disease that is not amenable to surgical resection or orthotopic liver transplantation or is metastatic in nature.

Detailed Description

The investigators are looking for men or women aged 18 years or older with hepatocellular carcinoma not suitable for surgical resection or hepatic transplantation. Prior locoregional therapy including but not limited to transarterial chemoembolization (TACE), radiofrequency ablation (RFA) or ethanol injection is allowed as long as the treatment was 4 weeks previous. Patients must be Child-Pugh A with no previous treatment with sorafenib or other vascular endothelial growth factor (VEGF) inhibitors.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma, Liver Cancer

Keywords

Cirrhosis, GI Cancer, Hepatitis, Oncology

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

47 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily

Arm Type

Experimental

Arm Description

Cohort 1: Participants were administered Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily

Arm Title

Bavituximab: 1.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Arm Type

Experimental

Arm Description

Cohort 2: Participants were administered Bavituximab:1.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Arm Title

Bavituximab: 3.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Arm Type

Experimental

Arm Description

Cohort 3: Participants were administered Bavituximab:3.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Intervention Type

Drug

Intervention Name(s)

bavituximab (0.3 mg/kg) and sorafenib

Intervention Description

Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily

Intervention Type

Drug

Intervention Name(s)

bavituximab (1.0 mg/kg ) and sorafenib

Intervention Description

Bavituximab: 1.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Intervention Type

Drug

Intervention Name(s)

bavituximab (3.0 mg/kg) and sorafenib

Intervention Description

Bavituximab: 3.0 mg/kg weekly Sorafenib: 400mg PO twice daily

Primary Outcome Measure Information:

Title

Median Radiographic Time to Progression (TTP) Calculated From Treatment Initiation to First Evidence of Disease Progression or Last Follow-up.

Description

Time Frame

Treatment initiation to first evidence of disease progression or last follow-up, an average of 24 months

Title

Number of Patients With Dose Limiting Toxicity

Description

Dose limiting toxicity by serious adverse events by CTCAE version 4.0

Time Frame

8 months.

Secondary Outcome Measure Information:

Title

Safety, as Measured by the Number of Patients With Adverse Event Related to the Treatment That Experienced Grade 3 or Greater.

Description

Safety was measured by the number of patients with at least one adverse event as assess by NCI Common Terminology criteria for adverse events (CTCAE)

Time Frame

Up to 3 months of patient enrollment (phase 1)

Title

Median Months of Overall Survival Calculated From Treatment Initiation to Death or Last Follow-up.

Description

Time Frame

Treatment initiation to death or last follow-up, an average 24 months

Title

Median Months of Disease Specific Survival Calculated From Treatment Initiation to Death From Advanced HCC (Hepatocellular Carcinoma) or Last Follow-up.

Description

Time Frame

Treatment initiation to first evidence of death from advanced liver cancer or last follow-up, an average of 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have a diagnosis of hepatocellular carcinoma by at least one criterion listed below: Histologically confirmed. MRI or CT consistent with liver cirrhosis and at least one solid liver lesion >2 cm with early enhancement and delayed enhancement washout regardless of AFP. AFP >400 ng/ml and evidence of at least one solid liver lesion >2 cm regardless of specific imaging characteristics on CT or MRI. Locally advanced or metastatic disease. Patients with locally advanced disease must have disease deemed to be unresectable or not eligible for hepatic transplantation. Determination will occur in the weekly GI DMT meeting by surgical oncologists and transplant surgeons. Measurable disease, as defined as lesions that can accurately be measured in at least one dimension (longest diameter to be measured) according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at least 2 cm with conventional techniques or at least 1 cm with spiral computed tomography. Child-Pugh Score A. Age ≥ 18 years. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2. Absolute neutrophil count ≥ 1,500 cells/mm3. Platelet count ≥ 75,000 cells/mm3. Total bilirubin ≤ 3.0 mg/dl. Hemoglobin ≥ 8.5 g/dl. AST and ALT ≤ 5.0 times upper limit of normal. D-dimer ≤ 3 times upper limit of normal. INR ≤ 1.8 (therapeutic anticoagulation allowed as long as medically indicated. Exclusion Criteria: History of bleeding diathesis or coagulopathy. Symptomatic or clinically active brain metastases. Major surgery within previous 4 weeks. History of thromboembolic events (including both pulmonary embolisms and deep vein thrombosis); central venous catheter-related thrombosis > 6 months prior is allowed. Prior adjuvant therapy with sorafenib or other Raf/MEK/RAS or VEGFR inhibitors. Prior adjuvant therapy is allowed provided it was completed > 6 months ago and there is documented recurrence of hepatocellular carcinoma.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Adam C Yopp, MD

Organizational Affiliation

UT Southwestern Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

UT Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31429027

Citation

Mokdad AA, Zhu H, Beg MS, Arriaga Y, Dowell JE, Singal AG, Yopp AC. Efficacy and Safety of Bavituximab in Combination with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Arm, Open-Label, Phase II Clinical Trial. Target Oncol. 2019 Oct;14(5):541-550. doi: 10.1007/s11523-019-00663-3.

Results Reference

derived

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Study of Bavituximab and Sorafenib In Patients With Advanced Liver Cancer

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