TACE Emulsion Versus Suspension

Study Overview
=================
Brief Summary
-----------------
The aim of the study was to evaluate the safety and efficacy of using the new formulation (Lipiodol-cisplatin suspension) for TACE in the treatment of HCC as compared to the conventional formulation (Lipiodol-cisplatin emulsion). This is a prospective, parallel-group, open-label randomized, phase II study that is conducted in accordance to the Declaration of Helsinki and international standards of Good Clinical Practice, and approved by the institutional review board. Eligible patients were randomized into either a treatment arm of Lipiodol-cisplatin suspension or a control arm of Lipiodol-cisplatin emulsion with a 1:1 ratio.

Detailed Description
-----------------
Transcatheter arterial chemoembolization (TACE) has been playing an important role in the treatment algorithm for patients with multifocal or large intrahepatic lesions not eligible for surgical resection, transplantation, or local ablative therapy. In Hong Kong, the TACE regimen currently being utilized in the great majority of hospitals is based on an aqueous form of cisplatin (1mg per mL) mixed in a one-to-one ratio by volume with Lipiodol to form a relatively large volume of 40mL emulsion at 20mg cisplatin as the maximum dose. Although TACE with this regimen has been shown to be effective in prolonging overall survival, there is probably room for further improvement because the objective tumor response rate is limited to 39%. One of the approaches to improve the treatment effectiveness of TACE could be to increase the dose of chemotherapeutic agent. In the United States, the most common regimen of chemotherapeutic agent in TACE is the mixture of cisplatin 100mg, doxorubicin 50mg, and mitomycin C 10mg, dissolved in 10ml of water-soluble contrast medium, then emulsified in an equivalent volume of lipiodol to form a 20mL emulsion. A relatively new regimen was introduced, in which a relatively high dose of cisplatin up to 100mg in particle form was given as a suspension in 20mL of Lipiodol, this regimen has been used and found to achieve an improved objective tumor response rate of 51%.

Official Title
-----------------
Lipiodol-based Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Randomized Controlled Trial of Aqueous Cisplatin Emulsion Versus Cisplatin Particle Suspension

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

Intervention / Treatment
-----------------
* Drug: Cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Age above 18 years HCC unsuitable for resection or ablation Child-Pugh A cirrhosis Eastern Cooperative Oncology Group performance score 0 or 1 BCLC A or B No previous treatment for HCC except for liver resection HCC diagnosed by typical enhancement patterns on cross sectional imaging or histology. No extra-hepatic involvement on non-enhanced CT thorax and triphasic contrast enhanced CT abdomen. No invasion of portal vein or hepatic vein Massive expansive tumor morphology with measurable lesion on CT (characterized by well-defined spherical or globular configuration, with or without tumor capsule or satellite lesions) Total tumor mass < 50% liver volume Size of any individual tumor <= 12cm in largest dimension Serum creatinine < 130 umol/L or Creatinine clearance > 55 ml/min. Exclusion Criteria: Known active malignancy within the last 3 years History of acute tumor rupture presenting with hemo-peritoneum Biliary obstruction not amenable to percutaneous or endoscopic drainage Child-Pugh B or C cirrhosis History of hepatic encephalopathy Intractable ascites not controllable by medical therapy History of variceal bleeding within last 3 months Infiltrative tumor morphology (characterized by ill- defined tumor margin and amorphous configuration) or diffuse tumor morphology (characterized by large number of small nodules) Incorrectable Arterio-portal venous shunt affecting >1 hepatic segment on CT Arterial-hepatic venous shunt with hepatic vein opacified in arterial phase on CT

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lipiodol-cisplatin suspension<br> | Drug: Cisplatin<br>* The procedure of TACE is the same irrespective of which regimen is used.<br>|
| Active Comparator: Lipiodol-cisplatin emulsion<br> | Drug: Cisplatin<br>* The procedure of TACE is the same irrespective of which regimen is used.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression (TTP) | The interval between the randomization date and the date of radiological progression, including intralesional progression, extralesional progression, or extra-hepatic progression. | within 30 days of a treatment procedure |