Sorafenib + mFOLFOX for Hepatocellular Carcinoma
Sorafenib + mFOLFOX for Hepatocellular Carcinoma
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.
After agreeing to participate in this study, the patient will be asked to undergo some
 screening tests or procedures to find out if he/she is eligible. Many of these tests and
 procedures are likely to be part of regular cancer care and may be done even if it turns out
 that the patient does not take part in the research study. If the patient has had some of
 these tests or procedures recently, they may or may not have to be repeated. These tests and
 procedures include: a medical history, physical exam, performance status, electrocardiogram,
 assessment of tumor, blood tests, urine test, pregnancy test and optional research biopsy. If
 these tests show that the patient is eligible to participate in the research study, he/she
 will begin the study treatment. If the patient does not meet the eligibility criteria, he/she
 will not be able to participate.

 If the patient takes part in this research study, he/she will be given a sorafenib study
 drug-dosing diary for each treatment cycle. Each treatment cycle lasts 28 days (4 weeks),
 during which time the patient will be taking the study drug twice daily. The diary will also
 include special instructions for sorafenib.

 There will be a 2-week Lead-in period, in which the patient will receive sorafenib alone for
 the first two weeks of the study. Cycle 1 will begin once the patient receives the
 combination sorafenib and FOLFOX.

 For FOLFOX, all three chemotherapy drugs will be injected through a central vein in the
 patient's chest (portacath) and will be given once every two weeks (14 days), starting on Day
 15 of Cycle 1. The patient will receive oxaliplatin first as a 2-hour infusion, followed by
 leucovorin, and then 5-FU. The 5-FU infusion can last up to 46 hours and will be given
 through a small portable pump. The investigator will ask the patient to come back to the
 clinic on day 3 (46 hours after begin 5-FU dose) for pump discontinuance.

 During all cycles the patient will have a physical exam and the patient will be asked
 questions about his/her general health and specific questions about any problems that he/she
 might be having and any medication he/she may be taking.

 As part of the research study the patient will undergo research blood tests that will measure
 certain proteins in the blood to learn what affect the study treatment may have on you and
 your disease. About 1 teaspoon of blood will be drawn on Days 3 and 14 during your first two
 weeks of sorafenib alone, again on Days 14 and 28 post-treatment with FOLFOX-sorafenib and,
 if available, at the time of progression (if the patient's disease gets worse).

 The patient's blood pressure will be monitored once every week for the first 6 weeks of the
 study (once a week during sorafenib lead-in period and Cycle 1). The investigator will asses
 the patient's tumor by chest, abdominal and pelvic CT or MRI scan once every 8 weeks
 throughout the study.

 After the final dose of the study drug the investigator will ask the patient to come back to
 the clinic to repeat the following procedures: medical review, physical examination, blood
 tests, pregnancy test and tumor assessment by CT or MRI. The investigator would like to keep
 track of patient's medical condition for the rest of his/her life. The investigator would
 like to do this by calling the patient on the telephone once a year to see how the patient is
 doing. Keeping in touch with the patient and checking his/her condition every year helps the
 investigator look at the long-term effects of the research study.
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