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

Carcinoma, Hepatocellular Clinical Trial

Official 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00919009
• Other study ID #: COTSUN Korea Trial
• Status: Completed
• Phase: Phase 2
• First received: April 27, 2009
• Last updated: May 29, 2012
• Start date: June 2009
• Est. completion date: December 2011

Study information

• Verified date: June 2009
• Source: National Cancer Center, Korea
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Procedure:
• TACE (Transcatheter Arterial Chemoembolization )
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

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Center, Korea

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability		1Year	Yes
Primary	Time to progression (TTP) in patients treated with TACE plus sorafenib		1year	No
Secondary	Progression free survival (PFS) will be evaluated		1year	No
Secondary	Overall response rate will be evaluated		1year	No