Comparison of Two Solvents Used With Chemotherapy Agent for Transarterial Chemoembolization of Hepatocellular Carcinoma

Study Overview
=================
Brief Summary
-----------------
TACE is considered the standard treatment for unresectable HCC and is widely used as a palliative treatment. However there is no consensus of the protocol of TACE.One of the variation is does the stability of the suspension by emulsified the lipiodol and the contrast medium used to dissolve the anticancer agents really effect the survival.Thus the investigators conduct this prospective,randomized controlled study to find out if the different method of preparing chemotheraputic drugs can cause a different survival benefit.

Detailed Description
-----------------
Transcatheter arterial chemoembolization is currently the mainstays of palliative treatments worldwide for patients with unresectable HCC. However there is no standard protocol exists for TACE currently. One of the controversy is does the way of emulsified the anticancer agents and lipiodol to get a high stability suspension really effect the survival rates. Anticancer drugs play important role in survival benefit. Many studies have innovated different methods to get a high stability suspension of lipiodol and anticancer drugs ,because they think lipiodol can selectively retained in HCC and used as a drug-carrying which allow a slow release of the anticancer drug from lipiodol microdroplets. Thus ,A stability suspension might get a maximize tumor drug uptake,which can caused a more tumor necrosis, and minimize systemic drug levels ,which get a less toxicity, hence survival benefit. While the other researcher think a stability emulsion can't get a positive effect ,such as pharmacokinetic and systematic toxicity of the anticancer drugs, tumor response, biologic response and so on.

Official Title
-----------------
Comparison of Two Solvents Used With Chemotherapy Agent for Transarterial Chemoembolization of Hepatocellular Carcinoma

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

Intervention / Treatment
-----------------
* Other: Solvent with specific gravity less than lipiodol
* Other: Solvent with specific gravity equivalent to lipiodol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients > 18 years and <=70 years of age with a diagnosis of HCC BCLC B stage disease Not amendable to surgical resection ,local ablative therapy and any other cured treatment. Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria. The lesion has not been previously treated with TACE, surgery, radiation therapy, radiofrequency ablation, percutaneous ethanol or acetic acid injection, or cryoablation. No Cirrhosis or cirrhotic status of Child-Pugh class A only Not pregnant or breast-feeding patients No significant renal impairment (creatinine clearance < 30 mL/minute) or patients on dialysis The following laboratory parameters: Platelet count ≥ 60,000/µL Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 1.5 mg/dL Serum albumin ≥ 35 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) >1,500/mm3 Ability to understand the protocol and to agree to and sign a written informed consent document Exclusion Criteria: Known history of HIV History of organ allograft Known or suspected allergy to the investigational agents or any agent given in association with this trial. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy Evidence of bleeding diathesis. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry. Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug Serious non-healing wound, ulcer, or bone fracture Known central nervous system tumors including metastatic brain disease severe Arterioportal Shunts or Arteria vein Shunts

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group1<br>Chemoembolization with solvent with specific gravity less than lipiodol | Other: Solvent with specific gravity less than lipiodol<br>* TACE with chemotherapy drugs (EADM 50mg, lobaplatin 50mg, and MMC 6mg)dissolved in distilled water and emulsified lipiodol followed embolization with polyvinyl alcohol particles (PVA)<br>|
| Experimental: group2<br>Chemoembolization with Solvent with specific gravity equivalent to lipiodol | Other: Solvent with specific gravity equivalent to lipiodol<br>* TACE with chemotherapy drugs (EADM 50mg, lobaplatin 50mg, and MMC 6mg)dissolved in water-soluble contrast medium and distilled water,then emulsified with lipiodol followed embolization with polyvinyl alcohol particles (PVA)<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  | 3 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Carcinoma,Hepatocellular, Liver Neoplasms, Survival analysis, treatment outcome, administration drugs, Chemoembolization,, TACE, polyvinyl alcohol, water-soluble contrast mesium, iopamidol, lipiodol, distilled water