The Role of Low Molecular Weight Heparins in Hepatocellular Carcinoma

Sponsor

Eastern Hepatobiliary Surgery Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00827554

Collaborator

(none)

100

Enrollment

Location

Arms

Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: LMWH Procedure: TACE	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2008

Actual Primary Completion Date :

Aug 1, 2011

Actual Study Completion Date :

Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LMWH plus TACE 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 Nadroparin Ca 4100 AXa iu twice daily lasted for 6 weeks Other Names: fraxiparine GlaxoSmithKline Procedure: TACE transarterial chemoembolization with lipiodol 1-1.5ml/cm tumor diametres，pharmorubicin 20mg，5-Fu 1g and Carboplatin 150mg。 Other Names: transarterial embolization/chemoembolization
Active Comparator: TACE alone 50 HCC patients randomly assigned to receive TACE without LMWH	Drug: LMWH Nadroparin Ca 4100 AXa iu twice daily lasted for 6 weeks Other Names: fraxiparine GlaxoSmithKline Procedure: TACE transarterial chemoembolization with lipiodol 1-1.5ml/cm tumor diametres，pharmorubicin 20mg，5-Fu 1g and Carboplatin 150mg。 Other Names: transarterial embolization/chemoembolization

Arm

Intervention/Treatment

Experimental: LMWH plus TACE

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

Nadroparin Ca 4100 AXa iu twice daily lasted for 6 weeks

Other Names:

fraxiparine

GlaxoSmithKline

Procedure: TACE

transarterial chemoembolization with lipiodol 1-1.5ml/cm tumor diametres，pharmorubicin 20mg，5-Fu 1g and Carboplatin 150mg。

Other Names:

transarterial embolization/chemoembolization

Active Comparator: TACE alone

50 HCC patients randomly assigned to receive TACE without LMWH

Drug: LMWH

Nadroparin Ca 4100 AXa iu twice daily lasted for 6 weeks

Other Names:

fraxiparine

GlaxoSmithKline

Procedure: TACE

transarterial chemoembolization with lipiodol 1-1.5ml/cm tumor diametres，pharmorubicin 20mg，5-Fu 1g and Carboplatin 150mg。

Other Names:

transarterial embolization/chemoembolization

Outcome Measures

Primary Outcome Measures

time-to-progression(TTP) [1 year]

Secondary Outcome Measures

The overall response rate [1 year]
Overall survival (OS) [1 year]
bleeding complication rate [6 weeks]
Progression Free Survival (PFS) [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.