Effectiveness and Safety Study of TACE Plus Oral Sorafenib for Unresectable HCC
Condition: Carcinoma, Hepatocellular
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Sorafenib; TACE
Intervention description: Oral sorafenib (400 mg BID) will start the next day after the first TACE treatment until unacceptable toxicity occurs, or until study termination.; TACE will be accomplished with gelatin microspheres (Embospheres) following delivery of 125 mg/m2 of cisplatin.
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Hepatocellular; Carcinoma; TACE; Sorafenib; Transcatheter Arterial Chemoembolization; Nexavar; Unresectable

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.
    

Eligibility criteria:

        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.