A Multi-center, Placebo-controlled, randomized pilot study of the effect of Sorafenib on Portal Pressure in Patients with Cirrhosis, Significant Portal Hypertension and Hepatocellular Carcinoma Treated with Ablative Therapy and/or Transarterial Chemoembolization

Trial Purpose and Description

Trial Purpose

This is a pilot proof-of-concept study that investigates the effect of sorafenib on portal pressure, as determined by the hepatic venous pressure gradient (HVPG), in patients with liver cirrhosis, portal hypertension and unresectable hepatocellular carcinoma (HCC) that has successfully responded to radiofrequency ablation and/or transarterial chemoembolization, and have obtained a complete response.

The primary end-point of the study is the achievement of at least a 10% reduction in HVPG observed from baseline to three months after starting treatment with sorafenib. Secondary end-point is the mean change in HVPG over this period (three months after initiation of sorafenib/placebo) and safety of sorafenib.

The trial is structured as a randomized double blind placebo controlled study. After a three-month period of therapy with sorafenib or placebo (double-blind phase), patients will be given open-label sorafenib for an additional 3-month period (open-label phase).  A total of 44 patients will be randomized (in the initial phase) on a 1:1 ratio to sorafenib or placebo.  Patients will be followed monthly and HCC follow-up will be according to standards of care. The study will be sponsored by Onyx, who will also provide the treatment medication (sorafenib and placebo)

Participation Guidelines

Eligibility Criteria

o   Age 20-75 years

o   Cirrhosis diagnosed by liver biopsy or by imaging studies showing a nodular liver, splenomegaly and/or collaterals

o   HCC proven histologically or diagnosed following the AASLD criteria if biopsy not feasible or refused by the patient

o   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))

o   CPT score <9 (that is all Child A and Child B with a score of 7 or 8)

o   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).

o   No more than two ablative procedures prior to enrollment

o   Clinically significant portal hypertension , as defined by HVPG ³10mmHg

o   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.

o   Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to  the start of treatment

o   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.

o   Signed informed consent

Sponsor:

Bayer

Onyx Pharmaceuticals

Dates:

August 2011

Last Updated:

Study HIC#:

1002006266

Clinicaltrials.gov ID: Yale8142467