Microparticle Enhanced Cytotoxic Transarterial Embolization Therapy in Hepatocellular Carcinoma

Study Overview
=================
Brief Summary
-----------------
This is a non-randomized, prospective, pilot, Multicenter Study of Drug-eluting bead transarterial chemoembolization (DEB-TACE) using Doxorubicin-Loaded Embozene® Tandem™ Microspheres to treat hepatocellular carcinoma (HCC).

Official Title
-----------------
Microparticle Enhanced Cytotoxic Transarterial Embolization Therapy in Hepatocellular Carcinoma

Conditions
-----------------
Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Device: TANDEM™


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with a confirmed diagnosis of HCC according to the European Association for the Study of the Liver (EASL) criteria for diagnosis, and staged according to the Barcelona clinic liver cancer (BCLC) criteria Subject is competent and willing to provide written informed consent in order to participate in the study Adults (male or female) patients ≥ 18 years of age Eastern Cooperative Oncology Group (ECOG) performance status 0-2 or Child Pugh classification is 0-11 Multidonar or single nodular tumor ≥3-10cm, Patients with bilobar disease who can be treated superselectively in a single session or both lobes able to be treated within 3-5 weeks. Patient must have at least one tumor lesion that meets the following criteria: Lesion can be accurately measured in at least one dimension according to modified Response Evaluation Criteria In Solid Tumors (mRECIST) criteria No invasion in the major blood vessel (hepatic portal, hepatic vein) or bile duct by the Magnetic resonance imaging (MRI) or Computed Tomography (CT) Proper blood, liver, renal, heart function: testing result within 2 weeks from registry of this study No current infections requiring antibiotic therapy Not actively on cumarin based anticoagulation or suffering from a known bleeding disorder Measurable disease per the Response Evaluation Criteria in Solid Tumors (mRECIST) Expected survival more than 6 months Exclusion Criteria: ECOG performance status >2; or Child-Pugh class C11 or more, or ASA class 5 Bilirubin levels >3 mg/dl HCC with large vessel or biliary duct invasion, diffuse HCC or extrahepatic spread Patients in which any of the following are contraindicated or present: The use of doxorubicin MRI Hepatic embolization procedures White blood cell (WBC) < 3000 cells/mm3 neutrophil < 1500 cells/mm3 Cardiac ejection fraction < 50 percent assessed by isotopic ventriculography, echocardiography or MR Elevated creatinine greater than or equal to 2.5 mg/dl Impaired clotting test (platelet count < 5 x 104/mm3, Prothrombin time-International normalized ratio (PT-INR > 2.0) aspartate transaminase (AST) and/or alanine transaminase (ALT) >5x ULN or, when greater >250 U/L Known hepatofugal blood flow Arterio-venous shunt Arterio-portal shunt Main stem portal vein occlusion(point 6 in inclusion criteria) Women who are pregnant or breast feeding Allergy to iodinated contrast used for angiography Tumour burden of more than 50% of liver Patients with objective signs of active bacterial, viral (human immunodeficiency virus (HIV)), or fungal infection Other primary malignancies or evidence of metastatic disease Patients previously treated with anthracyclines (other than doxorubicin). Any co-morbid disease or condition or event that, in the investigator's judgment, would place the patient at undue risk that would preclude the safe use of DEB-TACE. Under no circumstances should patients be enrolled in this study who is already participating in another study for treatment of primary liver cancer. Under no circumstances should patients be enrolled in this study who has received any other embolotherapy (including Selective Internal Radiation Therapy (SIRT)) for the treatment of primary liver cancer.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: DEB-TACE<br>Transarterial Chemoembolization with TANDEM™ - DOX Microspheres (DEB-TACE) Treatment: Lobes; Dosing: TANDEM™/Doxorubicin; Second Treatment:TANDEM™/Doxorubicin | Device: TANDEM™<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom From Serious Adverse Event (SAE) at 30days |  | Up to 30 days | 
| Freedom From Study Related SAE at 6 Months |  | Up to 6 months | 
| Freedom From Tumor Progression at 6 Months | Progression was assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST - Lencioni and Llovet 2010) as an increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12 Month Survival |  | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
To show safety, and efficacy, investigational product