A Multi-center pilot study of the effect of Sorafenib on Portal Pressure in Patients with Cirrhosis, Significant Portal Hypertension and Hepatocellular Carcinoma

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Health Professionals

Diseases and Conditions Researched

Hepatocellular Carcinoma

What is the purpose of this trial?

You are free to choose not to participate and if you do become a subject you are free to withdraw from this study at any time during its course. If you choose not to participate or if you withdraw it will not harm your relationship with your own doctors or with Yale-New Haven hospital. If you do become a subject, you are free to stop and withdraw from this study at any time during its course. If you sign this authorization, you may change your mind at any time, but the researchers may continue to use information collected before you changed your mind to complete the research. To withdraw, you can call a member of the research team at any time and tell them that you no longer want to take part. This will cancel any appointments in the future. You must also follow up your phone call by sending a written notice to revoke this authorization to the principal investigator, Dr. Strazzabosco, Internal Medicine - Digestive Diseases, PO BOX 208019, New Haven, CT 06520-8019. Before you make your decision, a member of the research team will be available so that you can ask any questions you have about the research project. You can ask for any information you want. Sign the consent form only after you have had a chance to ask your questions and have received satisfactory answers If you decide to withdraw from this project, please notify a member of the research team before you withdraw. This notice will allow that person or the research supervisor to inform you if there are any health risks or special requirements linked to withdrawing.

Participation Guidelines

Age: 20 Years - 75 Years
Gender: Both

Click here for detailed participation information for this trial.

Sponsors:	Bayer; Onyx Pharmaceuticals
Study HIC#:	1002006266

Official title

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

Condition

Hepatocellular Carcinoma

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

Age: 20 Years - 75 Years
Gender: Both

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