Bridge to Orthotopic Liver Transplantation (OLT) - Surefire Precision vs Endhole Embolization With DEBTACE

Study Overview
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Brief Summary
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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
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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.

Official Title
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SPEED 1 Trial: Bridge to Orthotopic Liver Transplantation (OLT) - (Surefire Precision vs Endhole Embolization With DEBTACE)

Conditions
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Hepatocellular Carcinoma of the Liver, Subjects Eligible for Liver Transplantation

Intervention / Treatment
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* Device: Surefire Precision Infusion System


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Fifty (50) subjects will be enrolled in the prospective arm.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DEB-TACE Procedure with Surefire Precision Infusion System<br>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. | Device: Surefire Precision Infusion System<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 months | 
| Time to Progression | For the outcome of time to progression, we will quantify the number of weeks from treatment until tumor progression. | Every 3 months through 24 months | 
| Survival Time | For the outcome of survival time, we will quantify the number of weeks from treatment until death. | Every 3 months through 24 months |