Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer
Condition: Advanced Adult Hepatocellular Carcinoma; Recurrent Hepatocellular Carcinoma; Stage III Hepatocellular Carcinoma AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7; Unresectable Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Doxorubicin Hydrochloride; Laboratory Biomarker Analysis; Pharmacogenomic Study; Sorafenib Tosylate
Intervention description: Given IV; Correlative studies; Correlative studies; Given PO
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Sorafenib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Enrollment: 356.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies sorafenib tosylate and doxorubicin hydrochloride to
      see how well they work compared with sorafenib tosylate alone in treating patients with liver
      cancer that has spread to nearby tissue or lymph nodes or has spread to other places in the
      body. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy,
      such as doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells,
      either by killing the cells or by stopping them from dividing. It is not yet known whether
      giving sorafenib tosylate together with doxorubicin hydrochloride is more effective than
      sorafenib tosylate alone in treating liver cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have pathologically or cytologically proven hepatocellular carcinoma;
             known mixed histology (e.g. hepatocellular carcinoma plus cholangiocarcinoma) or
             fibrolamellar variant is not allowed

          -  Patients must have locally advanced or metastatic disease; locally advanced disease is
             defined as disease deemed to be unresectable or non-eligible for transplant without
             distant metastases

          -  Lesions must be accurately measurable in at least one dimension (longest diameter to
             be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral
             computed tomography (CT) scan

          -  No prior adjuvant sorafenib or other v-RAF-1 murine leukemia viral oncogene homolog
             (Raf)/vascular endothelial growth factor (VEGF) inhibitors; other prior adjuvant
             therapy is allowed if completed > 6 months prior to registration with documented
             recurrence of hepatocellular carcinoma (HCC)

          -  Patients may have been treated with loco regional therapies provided that they either
             have:

               -  A target lesion that has not been subjected to local therapy or

               -  The target lesion(s) within the field of the local therapy has shown an increase
                  of >= 20% in the size since last treatment

                    -  Such therapy must be completed at least 4 weeks prior to registration;
                       patients that have received palliative radiation therapy to the bone need
                       not wait 4 weeks to begin protocol therapy

          -  Prior therapies allowed include the following:

               -  Bland embolization, radiation, radioactive microspheres, etc

               -  Chemoembolization using any chemotherapy (except, see below)

               -  Chemoembolization drug-eluting beads using doxorubicin

               -  Prior therapy with chemoembolization using doxorubicin in the non drug eluting
                  beads form is NOT allowed

          -  No prior systemic therapy for metastatic disease

          -  No prior exposure to systemic doxorubicin administered intravenously

          -  Antiviral treatment is allowed, however interferon therapy must be stopped at least 4
             weeks prior to registration

          -  Allografts are not allowed: no prior history of any allograft, including but not
             limited to liver and bone marrow transplants

          -  Patients must have completed any major surgery >= 4 weeks from registration

          -  Concomitant treatment with Rifampin or St John's wort is not allowed; patients should
             discontinue these drugs at least 4 weeks prior to registration

          -  No known central nervous system (CNS) tumors including brain metastases

          -  No clinically significant gastrointestinal bleeding events requiring intervention,
             transfusion, or admission to hospital within 30 days prior to registration

          -  Patients with a history of hypertension should be well controlled (< 140/90 mmHg) on a
             regimen of anti-hypertensive therapy

          -  Significant history of cardiac disease is not allowed:

               -  Congestive heart failure > class II New York Heart Association (NYHA)

               -  Myocardial infarction within 6 months prior to registration

               -  Serious myocardial dysfunction, defined as scintigraphically (multigated
                  acquisition scan [MUGA], myocardial scintigram) determined absolute left
                  ventricular ejection fraction (LVEF) below 45% or an LVEF on echocardiogram
                  (ECHO) below the normal limit at the individual institution

          -  No history of bleeding diathesis

          -  Patients receiving combination anti-retroviral therapy for human immunodeficiency
             virus (HIV) are excluded from the study

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Pregnancy/nursing status: women who are pregnant should not go on study; women should
             not breastfeed while participating in this study

          -  Granulocytes >= 1,500/uL

          -  Hemoglobin >= 8.5 g/dL; patients with recent or ongoing gastrointestinal bleed may not
             be transfused to reach the entry hemoglobin of 8.5 g/dL; physicians should ensure
             patients requiring transfusion prior to registration do not have an occult or
             clinically apparent gastrointestinal bleed

          -  Platelets >= 75,000/uL

          -  Creatinine =< 1.5 x upper limit of normal (ULN) (or creatinine clearance calculated >=
             60 cc/minute)

          -  Child-Pugh score A; patients must meet all laboratory value requirements

          -  Bilirubin =< 3 mg/dL

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 x ULN

          -  Prothrombin time (PT)-international normalized ratio (INR) =< 1.7 (not required for
             patients on anticoagulation agents; patients who are being therapeutically
             anticoagulated with an agent such as Coumadin or heparin will be allowed to
             participate provided that no prior evidence of underlying abnormality in these
             parameters exists)