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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


Phase 2
20 Years
75 Years
Open (Enrolling)
Both
Clinically Significant Portal Hypertension

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Trial Information

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


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)

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

Change in HVPG from baseline

Outcome Description:

Change in HVPG three months after initiation of sorafenib.

Outcome Time Frame:

Three Months

Safety Issue:

No

Principal Investigator

Guadalupe Garcia-Tsao, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Yale University

Authority:

United States: Institutional Review Board

Study ID:

HIC # 1002006266

NCT ID:

NCT01714609

Start Date:

August 2011

Completion Date:

August 2014

Related Keywords:

  • Clinically Significant Portal Hypertension
  • portal hypertension
  • sorafenib
  • Hypertension
  • Hypertension, Portal
  • Carcinoma, Hepatocellular

Name

Location

Yale Cancer CenterNew Haven, Connecticut  06520-8028
The University of Texas Health Science Center at HoustonHouston, Texas  77030