The Role of Low Molecular Weight Heparins in Hepatocellular Carcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ShenFeng, Eastern Hepatobiliary Surgery Hospital
ClinicalTrials.gov Identifier:
NCT00827554
First received: January 21, 2009
Last updated: March 30, 2016
Last verified: March 2016
  Purpose
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 Intervention Phase
Hepatocellular Carcinoma
Drug: LMWH
Procedure: TACE
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (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

Resource links provided by NLM:


Further study details as provided by Eastern Hepatobiliary Surgery Hospital:

Primary Outcome Measures:
  • time-to-progression(TTP) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The overall response rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • bleeding complication rate [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • Progression Free Survival (PFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: December 2008
Study Completion Date: October 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: transarterial embolization/chemoembolization

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.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adults patients with a diagnosis of HCC which is not amenable to surgical resection, liver transplantation or local ablative therapy
  2. Without metastasis out of liver
  3. Patients must have at least one tumor lesion that meets both of the following criteria:

    1. The lesion can be accurately measured in at least one dimension according to RECIST criteria
    2. The lesion has not been previously treated with surgery, radiation therapy, radiofrequency ablation, percutaneous ethanol or acetic acid injection, or cryoablation.
  4. ECOG performance status (PS) <2
  5. No prior targeted antiangiogenic therapy. Metronomic chemotherapies are allowed. At least 4 weeks since prior systemic chemotherapy
  6. Child-Pugh class A or B
  7. No significant renal impairment (creatinine clearance < 30 mL/minute) or patients on dialysis
  8. Ability to understand the protocol and to agree to and sign a written informed consent document -

Exclusion Criteria:

  1. HBSAg(-),AFP(-).
  2. prothrombin time prolonged more than 4s.
  3. blood platelets count less than 50000/L.
  4. Renal failure requiring dialysis.
  5. Child-Pugh class C hepatic impairment.
  6. clinically significant gastrointestinal bleeding within 30 days prior to study entry.
  7. History of organ allograft.
  8. Substance abuse (current), psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
  9. Known or suspected allergy to the investigational agents or any agent given in association with this trial.
  10. Pregnant or breast-feeding patients.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00827554

Locations
China, Shanghai
Eastern Hepatobiliary Surgery Hospital
ShangHai, Shanghai, China, 200438
Sponsors and Collaborators
Eastern Hepatobiliary Surgery Hospital
Investigators
Study Chair: Shen Feng, MD Eastern Hepatobiliary Surgery Hospital
  More Information

Responsible Party: ShenFeng, vice president of the Eastern Hepatobiliary Surgery Hospotal, Eastern Hepatobiliary Surgery Hospital
ClinicalTrials.gov Identifier: NCT00827554     History of Changes
Other Study ID Numbers: EHBH-RCT-2008-011 
Study First Received: January 21, 2009
Last Updated: March 30, 2016
Health Authority: China: Ministry of Health

Keywords provided by Eastern Hepatobiliary Surgery Hospital:
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

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Dalteparin
Heparin, Low-Molecular-Weight
Anticoagulants
Fibrin Modulating Agents
Fibrinolytic Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2016