Sorafenib + mFOLFOX for Hepatocellular Carcinoma
Condition: Hepatocellular Cancer
MeSH terms: Carcinoma, Hepatocellular; Liver Neoplasms
Intervention: Leucovorin; Fluorouracil; Oxaliplatin; Sorafenib
Intervention description: 200mg/m2 administered IV on Days 1 and 15 of a 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.; 5-FU continuous infusion: 2400mg/m2 total (1200mg/m2/d on day 1 and 2) to start on Day 1 and Day 15 of each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.; 85 mg/m2 IV on Days 1 and 15 of each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.; 400mg po BID continuously for a 2 week lead-in phase and then Days 1-28 of each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: sorafenib; FOLFOX

Summary:

      This research study is a Phase II clinical trial. Phase II clinical trials test the
      effectiveness of an investigational combination of drugs to learn whether the drug
      combination works in treating a specific cancer. "Investigational" means that the modified
      FOLFOX and sorafenib combination is still being studied and that research doctors are trying
      find out more about it-such as the safest dose to use, the side effects it may cause, and if
      the combination is effective for treating different types of cancer. It also means that the
      FDA has not yet approved the modified FOLFOX and sorafenib combination that will be used in
      this study for liver cancer.

      FOLFOX is a combination of three drugs: folinic acid (leucovorin), fluorouracil (5-FU), and
      oxaliplatin. The dosage amounts for some of these FDA approved drugs will be modified
      slightly in this study. The FOLFOX combination is approved by the FDA and is a standard
      treatment of colorectal cancer. However, it is not approved for the treatment of liver
      cancer.

      Sorafenib is a new drug, which is approved under the brand name Nexavar for the treatment of
      liver cancer. It is also currently being tested in various other cancers. Sorafenib works by
      slowing down and/or stopping the development of new cancer cells and new blood vessels. By
      slowing down and/or stopping the growth of new blood vessels around a tumor, it is believed
      that sorafenib prevents or slows down the growth of tumors.

      In this research study, sorafenib, the standard treatment, is being combined with modified
      FOLFOX, which has shown some antitumor activity in liver cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed advanced HCC

          -  Barcelona Clinic Liver Cancer stage C or stage B if you cannot tolerate or failed TACE

          -  No cirrhosis or Child-Pugh A cirrhosis

          -  Measurable lesions

          -  All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 grade 1
             or less

          -  Able to swallow and retain oral medication

        Exclusion Criteria:

          -  Prior systemic regimens for HCC

          -  Uncontrolled hypertension

          -  CLIP score > 3

          -  ECOG PS > 1

          -  Clinically apparent central nervous system metastases or carcinomatous meningitis

          -  Pregnant or breastfeeding

          -  Active or clinically significant cardiac disease

          -  Evidence or history of bleeding diathesis or coagulopathy

          -  Any pulmonary hemorrhage/bleeding event of NCI-CTCAE v4.0 Grade 2 or higher within 4
             weeks of enrollment

          -  Presence of a non-healing wound, non-healing ulcer, or bone fracture

          -  History of organ allograft

          -  Any malabsorption condition

          -  Medical or psychiatric condition that constitutes an unacceptable risk for
             participation in this trial

          -  Have received another investigational agent within 4 weeks of first dose of sorafenib

          -  Previously untreated or concurrent cancer except those treated more than 3 years ago

          -  History of other disease, metabolic dysfunction, physical examination finding or
             clinical laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that might affect the
             interpretation of the results of the study or render the subject at high risk from
             treatment complications

          -  QTC>500msec or history of uncontrolled angina, arrhythmias, or congestive heart
             failure

          -  Concurrent systemic and local anti-cancer therapy

          -  Prior use of sorafenib, oxaliplatin or 5FU

          -  Major surgery within 30 days

          -  Concurrent use of aspirin>100mg

          -  Therapeutic anticoagulation with vitamin K antagonists or with heparins or heparinoids