Sorafenib With Capecitabine for Patients With Measurable Hepatocellular Carcinoma
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Sorafenib & Capecitabine
Intervention description: Intervention: Sorafenib twice a day by mouth (400mg), Capecitabine twice a day by mouth (850mg). One cycle of treatment will consist of capecitabine on days 1-7 and 15-22 while sorafenib will be given daily continuously. Cycles will be repeated every 28 days.
Intervention MeSH terms: Capecitabine; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: INST 0820; sorafenib; capecitabine; hepatocellular carcinoma; lung; nexavar; xeloda; liver cancer

Summary:

      This research study will evaluate Sorafenib (Nexavar®) and Capecitabine (Xeloda®) to see the
      following:

        -  how effective this combination of study drugs will be in treating HCC

        -  how long subjects respond to these study drugs

        -  what types of side effects can be expected, and

        -  how severe the side effects are

      All subjects in this study will receive:

        -  Sorafenib twice a day by mouth

        -  Capecitabine twice a day by mouth

      Treatment will be given in a 28-day treatment cycle.

      Subjects will take sorafenib every day of the cycle. Subjects will take capecitabine on days
      1-7 and 15-21 of the cycle
    

Eligibility criteria:

        Inclusion Criteria:

        Histologic diagnosis of hepatocellular carcinoma The lesion or lesions are not resectable
        with curative intent. Prior loco-regional treatment (resection, RFA, chemoembolization) is
        allowed.

        Adequate bone marrow function:

          -  Absolute neutrophil count (AGC) >1500/µL

          -  Platelet count >60,000 /µL

        Renal function:

          -  Serum creatinine < 2.0 mg/dl, and a calculated CCT of > 30 mL/min. Hepatic
             function:(Patients with a Child-Pugh (C-P) class A-B)

          -  Bilirubin < 2.8 mg/dl (provided the Child-Pugh class of liver cirrhosis is A or B (7)
             (ie. The Child-Pugh score is only 7 points)

          -  ALT and AST ≤ 5.0 times the ULN • Hemoglobin > 8.5 g/dl

        ECOG/Zubrod/SWOG Performance Status = 0>1 Life expectancy > 16 weeks Male or female' age
        >18 years Patients of childbearing potential must be using an effective means of
        contraception.

        INR < 1.5 or a PT/PTT within normal limits.

        Exclusion Criteria:

          -  Any prior systemic therapy including chemotherapy of targeted agents

          -  Uncontrolled ascites defined as not easily controlled by stable doses of diuretics.

          -  Pregnant or lactating females

          -  Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have
             unstable angina (anginal symptoms at rest) or new onset angina (began within the last
             3 months) or myocardial infarction within the past 6 months.

          -  Uncontrolled' clinically significant dysrhythmia

          -  History of prior malignancy within the prior 3 years, with the exception of
             non-melanoma carcinomas of the skin, carcinoma in situ of the cervix or breast, Rai
             Stage I chronic lymphocytic leukemia and superficial bladder cancer.

          -  Prior radiotherapy to an indicator lesion unless there is objective evidence of tumor
             growth in that lesion

          -  Uncontrolled metastatic disease of the central nervous system

          -  Radiotherapy within the 2 weeks before Cycle 1' Day 1

          -  Surgery within the 2 weeks before Cycle 1' Day 1

          -  Any co morbid condition that' in the view of the attending physician' renders the
             patient at high risk from treatment complications.

          -  Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
             pressure > 90 mmHg, despite optimal medical management.

          -  Known human immunodeficiency virus (HIV) infection.

          -  Patients with chronic Hepatitis B or C infections are eligible.

          -  Active clinically serious infection > CTCAE Grade 2.

          -  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.

          -  Evidence or history of bleeding diathesis or coagulopathy.

          -  Use of St. John's Wort or rifampin (rifampicin).

          -  Known or suspected allergy to sorafenib or any agent given in the course of this
             trial.

          -  Any condition that impairs patient's ability to swallow whole pills.

          -  Any malabsorption problem.