The Effect of Sorafenib on Portal Pressure

Clinically Significant Portal Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01714609
• Other study ID #: 1002006266
• Status: Completed
• Phase: Phase 2
• Start date: August 2011
• Est. completion date: September 2014

Study information

• Verified date: December 2020
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 2014
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

• 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

Related Conditions & MeSH terms

• Clinically Significant Portal Hypertension
• Hypertension
• Hypertension, Portal

Intervention

Drug:
• Placebo
Placebo Comparator: Placebo
• Sorafenib
Sorafenib, 400 mg twice daily

Locations

Country	Name	City	State
United States	Brigham & Womens	Boston	Massachusetts
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	Yale Cancer Center	New Haven	Connecticut
United States	New York University Langone Medical Center	New York	New York
United States	University of Pennsylvania School of Medicine	Philadelphia	Pennsylvania
United States	VA Medical Center West Haven	West Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Onyx Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patients With Change in HVPG From Baseline	Number of participants with a decrease in HPVG that was > 10% of baseline	Three Months