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NCT Number: NCT00919009

Combination of Transcatheter Arterial Chemoembolization (TACE) and Sorafenib for Patients With Unresectable Hepatocellular Carcinoma (HCC)

Most HCC patients are diagnosed at advanced stages in Korea, transcatheter arterial chemoembolization is considered a key modality for palliative treatment in these HCC patients. TACE is currently one of the mainstays of palliative treatments worldwide for patients with inoperable HCC and it has shown survival benefits in patients with unresectable HCC. TACE consists primarily of directly targeted chemotherapy and embolization of arteries feeding the tumors, inevitably resulting in a hypoxic insult to HCC and surrounding liver tissues. Ischemic injury after TACE has been found to induce the upregulation of circulating vascular endothelial growth factor (VEGF), which is essential for tumor growth, invasion and metastasis in patients with HCC. Recent studies have shown a significant correlation between pre-TACE level of circulating VEGF or VEGF upregulation after TACE and HCC characteristics, including tumor size, vascular invasion, and metastasis. TACE consists primarily of directly targeted chemotherapy and embolization of arteries feeding the tumors, inevitably resulting in a hypoxic insult to HCC and surrounding liver tissues. Central tumor hypoxia was found to upregulate proangiogenic growth factors, which are potent mediators of tumor angiogenesis. Therefore, expression of circulating or tissue VEGF was enhanced after TACE in patients or animals with HCC, and there could be some probability of adverse effects of TACE in HCC patients.

In addition, the investigators demonstrated that a transient increment of serum VEGF level after TACE was significantly correlated with poor outcomes of tumor progression, especially outcomes relevant to distant metastasis.

Therefore, these findings suggest a rationale for applying adjuvant therapy with anti-angiogenesis agent additional treatment of anti-angiogenesis after TACE or during TACE in a selected group of patients HCC.

The aim of this study is to evaluate efficacy and safety of sorafenib 400 mg bid with TACE in patients with unresectable and/or inoperable HCC.

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Key information

Conditions

Carcinoma, Hepatocellular Adenocarcinoma Carcinoma Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

National Cancer Center

Seoul, South Korea

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients must provide signed written informed consent
  • Patients with clinical or histological diagnosis of HCC based on the guidelines of the Korean Liver Cancer Study Group and the National Cancer Center Korea
  • Patients with at least one, bi-dimensionally measurable lesion by multiphasic spiral CT scan or dynamic contrast-enhanced MRI
  • Patients with stage III or IVa HCC according to modified International Union Against Cancer TNM staging criteria without invasion in main portal vein, or inferior vena cava and extrahepatic metastasis and size of largest tumor 10cm at study entry
  • Patients with unresectable or inoperable HCC indicated for TACE as a treatment of choice according to the guidelines of the Korean Liver Cancer Study Group and the National Cancer Center Korea
  • Age ≥ 20 years
  • ECOG Performance Status of 0 or1
  • Child-Pugh class A or B (Child-Pugh score 7)
  • Life expectancy of at least 16 weeks
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
  • Hb ≧ 9g/dl
  • Absolute neutrophil count > 1000/mm3
  • Platelet count ≧ 60x109/L
  • Adequate clotting function: INR < 1.5
  • Hepatic: AST or ALT < 5 X ULN
  • Renal: serum creatinine < 1.5 x ULN
  • Bilirubin ≦ 3mg/dL

Exclusion criteria

  • Patients with diffuse infiltrative type of HCC that are poorly defined
  • Presence of hepatic encephalopathy and intractable ascites
  • Active clinically serious infections (> grade 2 NCI-CTC version 3.0), including spontaneous bacterial peritonitis
  • History of esophageal or gastric variceal bleeding
  • Patients who are on a liver transplant list
  • History of cardiac disease: congestive heart failure > NYHA class 2; active coronary artery disease (myocardial infarction more than 6 months prior to study entry is allowed), cardiac arrythmias requiring anti-arrythmic therapy or uncontrolled hypertension and diabetes mellitis
  • History of AIDS/HIV infection -Patients with seizure disorder requiring medication (such as steroids or anti- epileptics)
  • History of organ allograft
  • Patients with evidence or history of bleeding diathesis
  • Patients undergoing renal dialysis
  • Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1) or any cancer curatively treated > 3 years prior to study entry.

Treatment and study plan

TACE (Transcatheter Arterial Chemoembolization )

Procedure

TACE will be performed according to National Cancer Center protocol:

Briefly, an arterial catheter was inserted into the femoral artery by the Seldinger method and placed in the hepatic artery. Tumor feeding vessels were superselected where possible, the catheter was inserted to the level of the segmental arteries, subsegmental arteries, or lobar branches, and a solution containing 20-60 mg of doxorubicin hydrochloride (ADM; Dong-a Pharmacy, Seoul, Korea) and 2-20 mLof iodized oil (lipiodol) was infused through the catheter (5 French) or microcatheter (2.8 or 3 French). The dosage of doxorubicin and lipiodol was determined according to the tumor size, the presence of arteriovenous shunts or extrahepatic collateral vessels, and the underlying liver functions

Primary outcomes

  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    Time frame: 1Year

  2. Time to progression (TTP) in patients treated with TACE plus sorafenib

    Time frame: 1year

Secondary outcomes

  1. Progression free survival (PFS) will be evaluated

    Time frame: 1year

  2. Overall response rate will be evaluated

    Time frame: 1year

Sponsors and collaborators

Lead sponsor

National Cancer Center, Korea

Other Gov

Registry information

Official study title

A Phase II Study of the Combination of TACE and Sorafenib for Patients With Unresectable Hepatocellular Carcinoma in National Cancer Center Korea (COTSUN Korea Trial)

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Jun 11, 2009
Registry last updated
May 30, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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