The Effect of Sorafenib on Portal Pressure
Condition: Clinically Significant Portal Hypertension
MeSH terms: Hypertension, Portal; Hypertension
Intervention: Placebo; Sorafenib
Intervention description: Placebo Comparator: Placebo; Sorafenib, 400 mg twice daily
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 10.0
Sex: All
Minimum age: 20 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: portal hypertension; sorafenib

Summary:

      Sorafenib is approved by the US FDA for the treatment of unresectable (can not operate) liver
      cancer and for renal cell carcinoma. Sorafenib is a drug that inhibits the growth of cancer
      cells and prevents the formation of new blood vessels that would otherwise help the cancer
      spread.

      Studies in experimental animals have shown that sorafenib may also lower portal vein pressure
      (the pressure of the blood passing from the intestine through the liver.) This study seeks to
      determine if sorafenib lowers the blood pressure in liver blood vessels (portal vein
      pressure) in patients with cirrhosis who have high portal vein pressure. The study will also
      obtain information whether sorafenib is safe in this patient population.

      Half of the patients will be given sorafenib and half will be given a placebo (a pill without
      any medicine in it.) This allows a comparison of the reactions of people who take sorafenib
      to those who do not.
    

Eligibility criteria:

        -  Age 20-75 years

          -  Cirrhosis diagnosed by liver biopsy or by imaging studies showing a nodular liver,
             splenomegaly and/or collaterals

          -  HCC proven histologically or diagnosed following the AASLD criteria if biopsy not
             feasible or refused by the patient

          -  HCC must be unresectable and within UCSF criteria (single tumor ≤ 6.5 cm diameter, or,
             if multiple lesions, maximum diameter of the largest lesion ≤ 4.5 and total tumor
             diameter ≤ 8 cm (23))

          -  CPT score <9 (that is all Child A and Child B with a score of 7 or 8)

          -  Complete response to treatment with RFA (including that performed laparoscopically) or
             TACE or a combination of the above as defined by radiologic criteria (hepatoma
             protocol MRI or CT scan performed 4-6 weeks after the procedure).

          -  No more than two ablative procedures prior to enrollment

          -  Presence of portal hypertension, as defined by HVPG of >5 mmHg

          -  EGD for variceal screening performed within 6 months of entry into the study unless
             the patient is already on a stable dose of a non selective beta-blocker (adjusted to
             obtain a heart rate of 55-60 bpm) or treated with variceal band ligation.

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to the start of treatment

          -  Women of childbearing potential and men must agree to use adequate contraception
             (barrier method of birth control) prior to study entry and for the duration of study
             participation. Men should use adequate birth control for at least three months after
             the last administration of sorafenib.

          -  Signed informed consent