Chemoembolization With or Without Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery
Condition: Hepatocellular Carcinoma; Unresectable Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Cisplatin; Computed Tomography; Doxorubicin Hydrochloride; Doxorubicin-Eluting Beads; Laboratory Biomarker Analysis; Magnetic Resonance Imaging; Mitomycin; Pharmacological Study; Placebo Administration; Sorafenib Tosylate
Intervention description: Undergo TACE; Undergo CT scan; Undergo TACE; Undergo TACE; Correlative studies; Undergo MRI; Undergo TACE; Correlative studies; Given PO; Given PO
Intervention MeSH terms: Cisplatin; Doxorubicin; Liposomal doxorubicin; Sorafenib; Mitomycins; Mitomycin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 235.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies chemoembolization and sorafenib tosylate to see how
      well they work compared with chemoembolization alone in treating patients with liver cancer
      that cannot be removed by surgery. Drugs used in chemotherapy, such as doxorubicin
      hydrochloride, mitomycin, and cisplatin, work in different ways to stop the growth of tumor
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Chemoembolization kills tumor cells by carrying drugs directly into blood vessels
      near the tumor and then blocking the blood flow to allow a higher concentration of the drug
      to reach the tumor for a longer period of time. Kinase inhibitors, such as sorafenib tosylate
      may stop the growth of tumor cells by blocking the action of an abnormal protein that signals
      cancer cells to multiply. It is not yet known whether giving chemoembolization together with
      sorafenib tosylate is more effective than chemoembolization alone in treating patients with
      liver cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a diagnosis of hepatocellular carcinoma by at least one criterion
             listed below:

               -  Histologically confirmed

               -  Magnetic resonance imaging (MRI) or computerized tomography (CT) consistent with
                  liver cirrhosis AND at least one solid liver lesion > 2 cm with early enhancement
                  and delayed enhancement washout regardless of alpha-feto protein levels (AFP)

               -  AFP > 400 ng/mL AND evidence of at least one solid liver lesion > 2 cm regardless
                  of specific imaging characteristics on CT or MRI

          -  Patients must have hepatocellular carcinoma (HCC) limited to the liver; there must be
             no clinical or radiographic evidence of extrahepatic HCC

          -  Portal lymphadenopathy IS permitted for patients with hepatitis B virus (HBV) or
             hepatitis C virus (HCV) - as lymphadenopathy is commonly associated with hepatitis
             unrelated to malignancy

          -  Staging CT of the chest and CT or MRI of the abdomen and pelvis must have been
             completed within 4 weeks of study registration

          -  Patients must have measurable disease constituting < 50% of liver parenchyma within 4
             weeks of registration

          -  Patients may not have ascites detectable on physical examination

          -  Patients must not be candidates for curative resection, orthotopic liver
             transplantation, or radiofrequency ablation (RFA)

          -  Patients may have been treated with RFA in the past, but no sooner than 4 weeks before
             study registration

          -  Patients may have undergone previously attempted curative liver resection

          -  Patients may NOT have been previously treated with brachytherapy such as yttrium-90
             microsphere

          -  Patients may NOT have been previously treated with sorafenib, chemoembolization, or
             systemic chemotherapy including cytotoxic agents or molecularly targeted agents

          -  Branch portal vein invasion by tumor is permitted but patients with main portal vein
             invasion by tumor are not eligible

          -  Patients must have Child-Pugh score of A or B7 within 4 weeks prior to study
             registration

          -  Serum total bilirubin =< 2.0 mg/dL

          -  Alkaline phosphatase < 5 x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 5 x ULN

          -  Serum creatinine =< 1.5 mg/dL

          -  Platelet count >= 50,000/mm^3

          -  Patients must not have any evidence of bleeding diathesis or active gastrointestinal
             bleeding

          -  Patients must have no clinical signs of heart failure and meet New York Heart
             Association functional classification I or II defined as:

               -  Class I - patients with no limitation of activities; they suffer no symptoms from
                  ordinary activities

               -  Class II - patients with slight, mild limitation of activity; they are
                  comfortable with rest or with mild exertion

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0 or 1

          -  Patients must have a life expectancy of at least 3 months

          -  Patients must not be known to be human immunodeficiency virus (HIV) positive

          -  Patients must not have other uncontrolled intercurrent illnesses excluding HBV or HCV,
             including, but not limited to: uncontrolled hypertension, symptomatic congestive heart
             failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/addictive
             disorders that would limit compliance with study requirements

               -  Uncontrolled hypertension is defined as optimally treated baseline blood pressure
                  that exceeds 150/90 mm Hg

          -  Patients must not be taking cytochrome P450 enzyme inducing drugs

          -  Age >= 18 years

          -  Women must not be pregnant or breast-feeding; all females of childbearing potential
             must have a blood test or urine study within 2 weeks prior to registration to rule out
             pregnancy

          -  Women of childbearing potential and sexually active males must be strongly advised to
             use an accepted and effective method of contraception

          -  Patients must not have an allergy to iodine or gadolinium contrast that cannot be
             safely controlled with premedication

          -  Patient must be able to swallow pills, as study medications cannot be crushed