Hepatocellular Carcinoma of the Liver, Subjects Eligible for Liver Transplantation
Conditions
Brief summary
The purpose of this study will be to prospectively evaluate the outcomes of patients with hepatocellular carcinoma (HCC) who undergo DEB-TACE (drug-eluting bead trans-arterial chemoembolization) with the Surefire Precision Infusion System for intentional effect of down-staging patients to OLT. Patients with HCC and who are considered candidates for liver transplantation but outside Milancriteria and meet the eligibility criteria will be enrolled in the prospective single arm study. Results of the prospective cohort will be compared to matched historical control patients who were previously treated with DEB-TACE, delivered with standard endhole catheters. This includes all patients treated at the University of Colorado since 2009 treated with 100-300 micron beads for whom follow-up is available.
Detailed description
This is a single institution prospective clinical trial with historical matched controls. This protocol standardizes DEB-TACE delivery with the Surefire Precision Infusion System. This protocol does not change patient therapy. All patient safety monitoring, treatment procedures and follow-up procedures will be performed in accordance with standard clinical practice. Fifty (50) subjects will be enrolled in the prospective arm. Data from one hundred (100) historical randomly sampled control subjects (1:2 ratio) will be selected. Subjects will be followed at 1 week, 1 month, 3 months, then every 3 months, following the initial DEB-TACE procedure until the subject receives a liver transplant or death. The study will be concluded upon completion of enrollment and follow-up of the 50 patients. It is estimated that the time to complete patient enrollment and follow-up is 24 months. The estimated date for study completion (complete primary analyses) is June 2018. This is based on the average survival vs. time to transplant at this center. If there are individual patients that extend beyond this period the time may be slightly extended.
Interventions
DEVICESurefire Precision Infusion System
All patients enrolled in this protocol will receive DEB-TACE, which is the standard of care prescribed by their physician. Standard 5 Fr and 3 Fr catheters will be used to perform diagnostic angiography to map the hepatic vasculature to the tumor. Using standard technique, the target vessel feeding the tumor will be catheterized and DEB-TACE administered using the Surefire Precision catheter. The Doxorubicin dosing used in the DEB-TACE will be based upon tumor volume. DEB-TACE will be administered until the first of the following endpoints are reached: Achievement of target dose with stasis, leeching of contrast through the expandable tip and development of distal intrahepatic collaterals.
Sponsors
Surefire Medical, Inc.
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Fifty (50) subjects will be enrolled in the prospective arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients aged 18 years or older with the diagnosis of HCC currently being evaluated for liver transplantation and considered for downstaging. * Patients undergoing Surefire DEB-TACE procedure as clinically determined * Single tumor that is \>5 cm and less than 8 cm, OR 1 to 3 tumors with combined diameter greater than 15 cm and less than 24 cm * No portal invasion or extrahepatic spread * No previous chemotherapy, radiotherapy or transarterial embolization (with or without chemotherapy) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Preserved liver function (Child-Pugh Class A or B). * Discrete hepatic artery feeding the tumor with vessel diameter \> 1.5 mm
Exclusion criteria
* Advanced bilirubin levels \> 3 mg/dl * AST or ALT\>5 upper limit of normal or \>250 U/l * Advanced tumoral disease, defined as vascular invasion, extrahepatic spread, or diffuse HCC (50% liver involvement) * Contraindications for doxorubicin administration. * Child's Class C * Vessels providing flow to the tumor that are less than 1.5 mm in diameter
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local Recurrence Rate (LRR) | 6 months | For the outcome of local recurrence rate (LRR) we will test the null hypothesis of no difference in the proportion of patients with local recurrence by catheter type using a Fisher's exact test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response | 6 months | For the outcome of tumor response measured as the change in enhancing tumor size (pretreatment - post treatment) we will evaluate changes at 1 month and 6 month separately. |
| Time to Progression | Every 3 months through 24 months | For the outcome of time to progression, we will quantify the number of weeks from treatment until tumor progression. |
| Survival Time | Every 3 months through 24 months | For the outcome of survival time, we will quantify the number of weeks from treatment until death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DEB-TACE Procedure With Surefire Precision Infusion System The study duration for each patient is 24 months and includes a baseline visit, procedure visit and follow-up visits at 1 week, 1 month, 3 months, 6 months and every 3 months until liver transplant or death.
The following evaluations/activities will be performed at baseline: Informed consent, history, physical exam, data collection of CT/ MRI within 1 month of the visit date, data collection of lab values and quality of life questionnaire.
The treatment visit includes the DEB-TACE procedure with the Surefire Precision Infusion System. After the procedure, a Cone Beam CT of the liver will be performed to determine distribution and density of the beads in the tumor and adverse events monitoring.
The following evaluations / activities will be performed during the follow-up period: physical exam, data collection of contrast enhanced CT/MRI to evaluate tumor response, data collection of lab values, adverse event monitoring and quality of life questionnaire. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Early study termination | 3 |
| Overall Study | Protocol Violation | 5 |
Baseline characteristics
| Characteristic | DEB-TACE Procedure With Surefire Precision Infusion System |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 60.27 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 2 / 11 |
Outcome results
Primary
Local Recurrence Rate (LRR)
For the outcome of local recurrence rate (LRR) we will test the null hypothesis of no difference in the proportion of patients with local recurrence by catheter type using a Fisher's exact test.
Time frame: 6 months
Population: Zero participants analyzed as the study was terminated prior to data for outcome measures to be assessed. No data was collected or analyzed for this outcome measure.
Secondary
Survival Time
For the outcome of survival time, we will quantify the number of weeks from treatment until death.
Time frame: Every 3 months through 24 months
Population: Zero participants analyzed as the study was terminated prior to data for outcome measures to be assessed. No data was collected or analyzed for this outcome measure.
Secondary
Time to Progression
For the outcome of time to progression, we will quantify the number of weeks from treatment until tumor progression.
Time frame: Every 3 months through 24 months
Population: Zero participants analyzed as the study was terminated. No data was collected or analyzed for this outcome measure.
Secondary
Tumor Response
For the outcome of tumor response measured as the change in enhancing tumor size (pretreatment - post treatment) we will evaluate changes at 1 month and 6 month separately.
Time frame: 6 months
Population: Zero participants analyzed as the study was terminated prior to data for outcome measures to be assessed. No data was collected or analyzed for this outcome measure.