Sorafenib Tosylate and Chemoembolization With Doxorubicin Hydrochloride and Mitomycin in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery
Condition: Liver Cancer
MeSH terms: Liver Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: 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 and mitomycin, work in different ways to stop
      the growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Chemoembolization kills tumor cells by carrying drugs directly into the tumor and blocking
      the blood flow to the tumor. Giving sorafenib tosylate together with chemoembolization may
      kill more tumor cells.

      PURPOSE: This phase I trial is studying the side effects of sorafenib tosylate when given
      together with chemoembolization with doxorubicin hydrochloride and mitomycin in treating
      patients with liver cancer that cannot be removed by surgery.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To determine the safety of sorafenib tosylate when given in combination with
           transarterial chemoembolization (TACE) comprising doxorubicin hydrochloride and
           mitomycin C in patients with unresectable hepatocellular carcinoma.

      Secondary

        -  To estimate the time to progression (TTP) in patients treated with this regimen.

        -  To estimate the overall survival (OS) of patients treated with this regimen.

        -  To explore correlative relationships between measures of serum VEGF in the
           peri-procedure TACE period and changes with TACE and sorafenib tosylate as well as
           patient outcomes (TTP and OS).

      OUTLINE: This is a multicenter study.

      Patients receive oral sorafenib tosylate twice daily on days 1-14. Patients then undergo
      transarterial chemoembolization (TACE) comprising doxorubicin hydrochloride and mitomycin C
      on days 17-19*. Patients then receive oral sorafenib tosylate twice daily beginning after
      recovery from TACE and continuing in the absence of disease progression or unacceptable
      toxicity.

      NOTE: *A second course of TACE may be administered within 8 weeks after the first TACE
      procedure.

      Blood samples may be collected periodically for biomarker and pharmacokinetic analysis.

      After completion of study treatment, patients are followed up at 3-4 weeks and then every 3
      months for up to 3 years.
    

Intervention name(s): doxorubicin hydrochloride; mitomycin C; sorafenib tosylate; laboratory biomarker analysis; pharmacological study
Intervention type(s): Drug; Drug; Drug; Other; Other
Intervention description(s): TACE (day 18-20): Doxorubicin 50mg and mitomycin C 10mg mixed with lipoidal and injected in proportion to liver volume being treated, followed by embospheres. Administered until there is a "pruned tree" appearance on angiography. If a second TACE is to be performed it should be performed within 8 weeks of the first procedure.; TACE (day 18-20): Doxorubicin 50mg and mitomycin C 10mg mixed with lipoidal and injected in proportion to liver volume being treated, followed by embospheres. Administered until there is a "pruned tree" appearance on angiography. If a second TACE is to be performed it should be performed within 8 weeks of the first procedure.; Sorafenib 400mg BID continuously post TACE beginning when LFTs return to entry criterion. Discontinue at time of disease progression (progression in a lobe that has already been embolized, new lesions in an untreated lobe, or evidence of extrahepatic progression).; Serum VEGF levels are required: pre TACE (day of procedure, time B), 24 hours post TACE (+/- 6 hours, time C), day 7 post first TACE (± 1 day, time D), day 28 post reinitiation of sorafenib (± 3 days, time E). These levels will not be repeated for patients receiving a second TACE procedure.; Treatment with sorafenib will continue on a daily basis until disease progression (see definition protocol Section 7) or unacceptable toxicity is encountered. At the end of treatment, no further therapies are currently recommended.
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Mitomycins; Mitomycin; Sorafenib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult primary hepatocellular carcinoma; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer