Hepatocellular Carcinoma, Liver Cancer
Conditions
Keywords
Cirrhosis, GI Cancer, Hepatitis, Oncology
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.
Interventions
DRUGbavituximab (0.3 mg/kg) and sorafenib
Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily
DRUGbavituximab (1.0 mg/kg ) and sorafenib
Bavituximab: 1.0 mg/kg weekly Sorafenib: 400mg PO twice daily
DRUGbavituximab (3.0 mg/kg) and sorafenib
Bavituximab: 3.0 mg/kg weekly Sorafenib: 400mg PO twice daily
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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. 2. Locally advanced or metastatic disease. 3. 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. 4. 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. 5. Child-Pugh Score A. 6. Age ≥ 18 years. 7. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2. 8. Absolute neutrophil count ≥ 1,500 cells/mm3. 9. Platelet count ≥ 75,000 cells/mm3. 10. Total bilirubin ≤ 3.0 mg/dl. 11. Hemoglobin ≥ 8.5 g/dl. 12. AST and ALT ≤ 5.0 times upper limit of normal. 13. D-dimer ≤ 3 times upper limit of normal. 14. INR ≤ 1.8 (therapeutic anticoagulation allowed as long as medically indicated.
Exclusion criteria
1. History of bleeding diathesis or coagulopathy. 2. Symptomatic or clinically active brain metastases. 3. Major surgery within previous 4 weeks. 4. History of thromboembolic events (including both pulmonary embolisms and deep vein thrombosis); central venous catheter-related thrombosis \> 6 months prior is allowed. 5. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Radiographic Time to Progression (TTP) Calculated From Treatment Initiation to First Evidence of Disease Progression or Last Follow-up. | Treatment initiation to first evidence of disease progression or last follow-up, an average of 24 months | 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 | 8 months. | Dose limiting toxicity by serious adverse events by CTCAE version 4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety, as Measured by the Number of Patients With Adverse Event Related to the Treatment That Experienced Grade 3 or Greater. | Up to 3 months of patient enrollment (phase 1) | 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. | Treatment initiation to death or last follow-up, an average 24 months | 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. | Treatment initiation to first evidence of death from advanced liver cancer or last follow-up, an average of 12 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bavituximab:0.3 mg/kg Weekly Sorafenib: 400mg PO Twice Daily Cohort 1: Participants were administered Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily | 3 |
| Bavituximab: 1.0 mg/kg Weekly Sorafenib: 400mg PO Twice Daily Cohort 2: Participants were administered Bavituximab:1.0 mg/kg weekly Sorafenib: 400mg PO twice daily | 3 |
| Bavituximab: 3.0 mg/kg Weekly Sorafenib: 400mg PO Twice Daily Cohort 3: Participants were administered Bavituximab:3.0 mg/kg weekly Sorafenib: 400mg PO twice daily | 41 |
| Total | 47 |
Baseline characteristics
| Characteristic | 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 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 8 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 33 Participants | 37 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 16 Participants | 17 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 2 Participants | 10 Participants | 13 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 0 Participants | 13 Participants | 14 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 7 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 34 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 38 / 41 |
| other Total, other adverse events | 0 / 3 | 0 / 3 | 12 / 41 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 41 |
Outcome results
Primary
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.
Time frame: Treatment initiation to first evidence of disease progression or last follow-up, an average of 24 months
Population: Cohort 1 and 2 were part of phase 1 study and at the phase 1 study this outcome was not collected. The 3 participants who received dose Bavituximab: 3.0 mg/kg weekly Sorafenib: 400mg PO twice daily were part of phase 1 and hence they were not part of phase 2 . Hence their data were not analyzed here.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 3 | Median Radiographic Time to Progression (TTP) Calculated From Treatment Initiation to First Evidence of Disease Progression or Last Follow-up. | 6.7 months |
Primary
Number of Patients With Dose Limiting Toxicity
Dose limiting toxicity by serious adverse events by CTCAE version 4.0
Time frame: 8 months.
Population: This outcome was for phase 1 only
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Number of Patients With Dose Limiting Toxicity | 0 participants |
| Cohort 2 | Number of Patients With Dose Limiting Toxicity | 0 participants |
| Cohort 3 | Number of Patients With Dose Limiting Toxicity | 0 participants |
Secondary
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.
Time frame: Treatment initiation to first evidence of death from advanced liver cancer or last follow-up, an average of 12 months
Population: Cohort 1 and 2 were part of phase 1 study and at the phase 1 study this outcome was not collected. The 3 participants who received dose Bavituximab: 3.0 mg/kg weekly Sorafenib: 400mg PO twice daily were part of phase 1 and hence they were not part of phase 2 . Hence their data were not analyzed here.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 3 | Median Months of Disease Specific Survival Calculated From Treatment Initiation to Death From Advanced HCC (Hepatocellular Carcinoma) or Last Follow-up. | 8.6 months |
Secondary
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.
Time frame: Treatment initiation to death or last follow-up, an average 24 months
Population: Cohort 1 and 2 were part of phase 1 study and at the phase 1 study this outcome was not collected. The 3 participants who received dose Bavituximab: 3.0 mg/kg weekly Sorafenib: 400mg PO twice daily were part of phase 1 and hence they were not part of phase 2 . Hence their data were not analyzed here.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 3 | Median Months of Overall Survival Calculated From Treatment Initiation to Death or Last Follow-up. | 6.1 months |
Secondary
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)
Time frame: Up to 3 months of patient enrollment (phase 1)
Population: This outcome measure was only analyzed for phase 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Safety, as Measured by the Number of Patients With Adverse Event Related to the Treatment That Experienced Grade 3 or Greater. | 0 Participants |
| Cohort 2 | Safety, as Measured by the Number of Patients With Adverse Event Related to the Treatment That Experienced Grade 3 or Greater. | 0 Participants |
| Cohort 3 | Safety, as Measured by the Number of Patients With Adverse Event Related to the Treatment That Experienced Grade 3 or Greater. | 0 Participants |