The Effect of Sorafenib on Portal Pressure

December 2, 2020 updated by: Yale University

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

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.

Study Overview

Status

Completed

Intervention / Treatment

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

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale Cancer Center
      • West Haven, Connecticut, United States, 06516
        • VA Medical Center West Haven
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham & Womens
    • New York
      • New York, New York, United States, 10016
        • New York University Langone Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania School of Medicine
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas Health Science Center at Houston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.
Placebo Comparator: Placebo
Experimental: Sorafenib
Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.
Sorafenib, 400 mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patients With Change in HVPG From Baseline
Time Frame: Three Months
Number of participants with a decrease in HPVG that was > 10% of baseline
Three Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Investigators

  • Principal Investigator: Guadalupe Garcia-Tsao, MD, Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2011

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

October 23, 2012

First Submitted That Met QC Criteria

October 23, 2012

First Posted (Estimate)

October 26, 2012

Study Record Updates

Last Update Posted (Actual)

December 29, 2020

Last Update Submitted That Met QC Criteria

December 2, 2020

Last Verified

December 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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