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

May 29, 2012 updated by: Joong-Won Park, National Cancer Center, Korea

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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sorafeinb
Oral sorafenib (400 mg BID) will be start the 3 day after the first TACE treatment and will continue until the patient shows disease progression, until unacceptable toxicity occurs, or until study termination.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: 1Year
1Year
Time to progression (TTP) in patients treated with TACE plus sorafenib
Time Frame: 1year
1year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Progression free survival (PFS) will be evaluated
Time Frame: 1year
1year
Overall response rate will be evaluated
Time Frame: 1year
1year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Cancer Center, Korea

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Joong-Won Park, Ph.D., National Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 27, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 10, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 11, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 30, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • COTSUN Korea Trial

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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