The Role of Low Molecular Weight Heparins in Hepatocellular Carcinoma

Study Overview
=================
Brief Summary
-----------------
Hepatocellular carcinoma (HCC) is a major tumor type worldwide, especially in China as the sequence of hepatitis B and liver cirrhosis. Activation of the coagulation system occurs commonly in patients with malignancy. Several studies have suggested that anticoagulant therapy may improve survival in patients with malignancy. The low molecular weight heparins (LMWHs) lend themselves to such studies because of their effects in experimental models of malignancy and the relative ease of administration compared with unfractionated heparin. The purpose of the present RCT was to determine whether addition of LMWH to transarterial chemoembolization (TACE) would improve HCC patient outcome compared with TACE alone.

Detailed Description
-----------------
100 patients will be randomly assigned to receive either TACE alone or TACE plus LMWH. A block of every 4 participants and a stratified randomization according to portal vein cancer emboli will be used to restrict randomization. LMWH consisted of nadroparin Ca will be given at a dose of 4100 U twice daily during 6 weeks after TACE. The time to progression(TTP) and overall survival within two years will be used to evaluate the effect of LMWH on HCC.

Official Title
-----------------
A Clinical Randomized Control Trial of Combination TACE With and Without Low-molecular-weight Heparin in Hepatocellular Carcinoma

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

Intervention / Treatment
-----------------
* Drug: LMWH
* Procedure: TACE


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults patients with a diagnosis of HCC which is not amenable to surgical resection, liver transplantation or local ablative therapy Without metastasis out of liver Patients must have at least one tumor lesion that meets both of the following criteria: The lesion can be accurately measured in at least one dimension according to RECIST criteria The lesion has not been previously treated with surgery, radiation therapy, radiofrequency ablation, percutaneous ethanol or acetic acid injection, or cryoablation. ECOG performance status (PS) <2 No prior targeted antiangiogenic therapy. Metronomic chemotherapies are allowed. At least 4 weeks since prior systemic chemotherapy Child-Pugh class A or B No significant renal impairment (creatinine clearance < 30 mL/minute) or patients on dialysis Ability to understand the protocol and to agree to and sign a written informed consent document - Exclusion Criteria: HBSAg(-)，AFP(-). prothrombin time prolonged more than 4s. blood platelets count less than 50000/L. Renal failure requiring dialysis. Child-Pugh class C hepatic impairment. clinically significant gastrointestinal bleeding within 30 days prior to study entry. History of organ allograft. Substance abuse (current), psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. Known or suspected allergy to the investigational agents or any agent given in association with this trial. Pregnant or breast-feeding patients.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LMWH plus TACE<br>50 HCC patients will be allocated to receive Nadroparin 4100 AXa iu twice daily 3 days after TACE which lasted for 6 weeks | Drug: LMWH<br>* Nadroparin Ca 4100 AXa iu twice daily lasted for 6 weeks<br>* Other names: GlaxoSmithKline;Procedure: TACE<br>* transarterial chemoembolization with lipiodol 1-1.5ml/cm tumor diametres，pharmorubicin 20mg，5-Fu 1g and Carboplatin 150mg。<br>* Other names: transarterial embolization/chemoembolization;|
| Active Comparator: TACE alone<br>50 HCC patients randomly assigned to receive TACE without LMWH | Drug: LMWH<br>* Nadroparin Ca 4100 AXa iu twice daily lasted for 6 weeks<br>* Other names: GlaxoSmithKline;Procedure: TACE<br>* transarterial chemoembolization with lipiodol 1-1.5ml/cm tumor diametres，pharmorubicin 20mg，5-Fu 1g and Carboplatin 150mg。<br>* Other names: transarterial embolization/chemoembolization;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time-to-progression(TTP) |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The overall response rate |  | 1 year | 
| Overall survival (OS) |  | 1 year | 
| bleeding complication rate |  | 6 weeks | 
| Progression Free Survival (PFS) |  | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Liver Neoplasms, Liver Diseases, Digestive System Diseases, Digestive System Neoplasms, Carcinoma, Hepatocellular, Gastrointestinal Neoplasms, Adenocarcinoma, Hepatocellular carcinoma, Neoplasms, Transarterial chemoembolization, Nadroparin, low-molecular-weight heparin, chemoembolization