Pilot Study of Effect of Sorafenib on Portal Pressure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01714609
Recruitment Status : Completed
First Posted : October 26, 2012
Results First Posted : December 9, 2015
Last Update Posted : December 9, 2015
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
Yale University

Brief 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.

Condition or disease Intervention/treatment Phase
Clinically Significant Portal Hypertension Drug: Placebo Drug: Sorafenib Phase 2

Detailed Description:

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 change in HVPG observed from baseline to three months after starting treatment with sorafenib. Secondary end-point is 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)

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-Center, Placebo-Controlled Randomized Pilot of the Effect of Sorafenib on Portal Pressure in Patients With Cirrhosis, Portal Hypertension and Hepatocellular Carcinoma Treated With Ablative Therapy and/or Transarterial Chemoembolization
Study Start Date : August 2011
Actual Primary Completion Date : September 2013
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo
Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.
Drug: Placebo
Placebo Comparator: Placebo

Experimental: Sorafenib
Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.
Drug: Sorafenib
Sorafenib, 400 mg twice daily

Primary Outcome Measures :
  1. Patients With Change in HVPG From Baseline [ Time Frame: Three Months ]
    Number of participants with a decrease in HPVG that was > 10% of baseline

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01714609

United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520
VA Medical Center West Haven
West Haven, Connecticut, United States, 06516
United States, Massachusetts
Brigham & Womens
Boston, Massachusetts, United States, 02115
United States, New York
New York University Langone Medical Center
New York, New York, United States, 10016
United States, Pennsylvania
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
The University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
Yale University
Onyx Therapeutics, Inc.
Principal Investigator: Guadalupe Garcia-Tsao, MD Yale University

Responsible Party: Yale University Identifier: NCT01714609     History of Changes
Other Study ID Numbers: HIC # 1002006266
First Posted: October 26, 2012    Key Record Dates
Results First Posted: December 9, 2015
Last Update Posted: December 9, 2015
Last Verified: November 2015

Keywords provided by Yale University:
portal hypertension

Additional relevant MeSH terms:
Hypertension, Portal
Vascular Diseases
Cardiovascular Diseases
Liver Diseases
Digestive System Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs