Effectiveness and Safety Study of TACE Plus Oral Sorafenib for Unresectable HCC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00576056
Recruitment Status : Terminated (Bayer Healthcare is no supplying the study drug)
First Posted : December 18, 2007
Results First Posted : December 28, 2016
Last Update Posted : February 15, 2017
Information provided by (Responsible Party):
Susan Lamson, RN, BA, University of Pittsburgh

Brief Summary:
The purpose of this study is to determine if TACE plus Sorafenib will improve outcome in patients with advanced hepatocellular carcinoma (HCC) not amenable to surgery.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Drug: Sorafenib Drug: TACE Phase 2

Detailed Description:
The proposed study will make an important contribution to understanding not only the safety and efficacy of sorafenib in addition to TACE in patients diagnosed with unresectable HCC, but this will also be the first clinical trial with sorafenib to assess the effects of this novel therapy on HRQL. Understanding the effects of sorafenib on HRQL is critical in the treatment of HCC secondary to the modest benefits in survival that have been reported with conventional therapies. Our team has one of the largest experiences in evaluating HRQL in patients diagnosed with unresectable hepatocellular carcinoma. We have previously reported on alternative methods of evaluating HRQL, solutions for missing data in clinical trials as well as tested statistical and clinically meaningful differences, within and between treatment groups, in clinical trials with patients diagnosed with hepatobiliary carcinoma.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Transcatheter Arterial Chemoembolization (TACE) Plus Oral Sorafenib (BAY 43-9006, Nexavar®) for Unresectable Hepatocellular Carcinoma (HCC)
Study Start Date : January 2008
Actual Primary Completion Date : March 2010
Actual Study Completion Date : April 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Tace and Sorafenib
Patients with unresectable HCC will be treated with TACE in combination with oral sorafenib administration. TACE will be accomplished with gelatin microspheres (Embospheres) following delivery of 125 mg/m2 of cisplatin. Oral sorafenib (400 mg BID) will start the next day after the first TACE treatment.
Drug: Sorafenib
Oral sorafenib (400 mg BID) will start the next day after the first TACE treatment until unacceptable toxicity occurs, or until study termination.
Other Name: Nexavar
Drug: TACE
TACE will be accomplished with gelatin microspheres (Embospheres) following delivery of 125 mg/m2 of cisplatin.
Other Name: Transarterial Chemoembolization

Primary Outcome Measures :
  1. Determine Progression-free Survival in This Patient Population Treated With the Proposed Combination Treatment Modality [ Time Frame: Up to 24 months (from initial treatment through 12 months follow-up) ]
    Progression free survival (PFS) is calculated as the time interval between the date on which a patient first received protocol treatment and the documented date of disease progression or death. For a surviving and progression-free patient, PFS is censored by the last follow-up date when that patient is documented to be progression free. Progression is defined using RECIST v1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.

Secondary Outcome Measures :
  1. Determine the Overall Survival in Patients Treated With This Combination Regimen [ Time Frame: From date of initial treatment until the date of death from any cause ]
    Overall survival (OS) is calculated as the time interval between the date on which a patient first received protocol treatment and the documented date of death. For a surviving patient, OS is censored by the last follow-up date when that patient is documented to be alive.

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult patients with HCC seen at UPMC will be enrolled in this study if they meet the following eligibility criteria:
  • Adults patients (≥ 18 years of age) with a diagnosis of HCC which is not amenable to surgical resection or local ablative therapy
  • Histological confirmed HCC or clinical/laboratory diagnosis of HCC or nodules larger than 2 cm with typical vascular features or AFP > 200
  • Patient must have quantifiable disease limited to the 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
  • At least 4 weeks since prior TACE
  • At least 4 weeks since prior interferon
  • Not pregnant
  • No significant baseline liver dysfunction. Cirrhotic status of Child-Pugh class A only
  • No significant renal impairment (creatinine clearance < 30 mL/minute) or patients on dialysis
  • No current infections requiring antibiotic therapy
  • Not on anticoagulation or suffering from a known bleeding disorder
  • No unstable coronary artery disease or recent MI
  • The following laboratory parameters:

    • Platelet count ≥ 60,000/µL
    • Hemoglobin ≥ 8.5 g/dL
    • Total bilirubin ≤ 1.5 mg/dL
    • ASL and AST ≤ 5 x upper limit of normal
    • Serum creatinine ≤ 1.5 x upper limit of normal
    • INR ≤ 1.5 or a Pt/PTT within normal limits
    • Absolute neutrophil count (ANC) > 1,500/mm3
  • Ability to understand the protocol and to agree to and sign a written informed consent document

Exclusion Criteria:

  • Previous or concurrent cancer that is distinct in primary site or histology from HCC except cervical carcinoma in situ, treated basal-cell carcinoma of the skin, superficial bladder tumors (Ta, Tis & T1), and any cancer curatively treated > 3 years prior to entry is permitted
  • Renal failure requiring hemo- or peritoneal dialysis
  • Child-Pugh B & C hepatic impairment
  • History of cardiac disease: > NY Heart Association (NYHA) class 2 congestive heart failure, active coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, and uncontrolled hypertension. Myocardial infarction more than 6 months prior to study entry is permitted.
  • Active clinically serious infections (> CTCAEv3 grade 2)
  • Known history of HIV
  • Known central nervous system tumors including metastatic brain disease
  • 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.
  • Patients unable to swallow oral medications.
  • Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of the study drug. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg, despite optimal medical management
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
  • Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug
  • Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug
  • Serious non-healing wound, ulcer, or bone fracture

Excluded therapies and medications, previous and concomitant:

  • Prior use of Raf-kinase inhibitors (RKI), VEGF inhibitors, MEK inhibitors, or farnesyl transferase inhibitors
  • Major surgery within 6 weeks of start of study drug
  • Radiotherapy during study or within 3 weeks prior to start of study drug.
  • Use of biologic response modifiers such as granulocyte colony-stimulating factor (G-CSF) within 3 weeks prior to study entry.
  • Autologous bone marrow transplant or stem cell rescue within four months of study drug initiation
  • Concomitant treatment with rifampin or St. John's wort.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00576056

United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
University of Pittsburgh
Principal Investigator: Thomas C Gamblin, MD University of Pittsburgh

Responsible Party: Susan Lamson, RN, BA, RN BA, University of Pittsburgh Identifier: NCT00576056     History of Changes
Other Study ID Numbers: 07-047
First Posted: December 18, 2007    Key Record Dates
Results First Posted: December 28, 2016
Last Update Posted: February 15, 2017
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Susan Lamson, RN, BA, University of Pittsburgh:
Transcatheter Arterial Chemoembolization

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs
Estrogens, Non-Steroidal
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal