Clinical trial NCT01714609: The Effect of Sorafenib on Portal Pressure
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Clinically Significant Portal Hypertension
Keywords: portal hypertension
sorafenib
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Onyx Therapeutics, Inc.
First posted: 2012-10-26
Enrollment: 10
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Eligibility criteria: * 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

Primary outcomes:
measure: Patients With Change in HVPG From Baseline
timeFrame: Three Months
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: West Haven
country: United States
facility: VA Medical Center West Haven
state: Connecticut
city: Boston
country: United States
facility: Brigham & Womens
state: Massachusetts
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania School of Medicine
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: Yale University
name: Guadalupe Garcia-Tsao, MD
role: PRINCIPAL_INVESTIGATOR
References: