Pilot Study of Effect of Sorafenib on Portal Pressure

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Yale University
Sponsor:
Collaborator:
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
Guadalupe Garcia-Tsao, Yale University
ClinicalTrials.gov Identifier:
NCT01714609
First received: October 23, 2012
Last updated: NA
Last verified: October 2012
History: No changes posted

October 23, 2012
October 23, 2012
August 2011
August 2013   (final data collection date for primary outcome measure)
Change in HVPG from baseline [ Time Frame: Three Months ] [ Designated as safety issue: No ]
Change in HVPG three months after initiation of sorafenib.
Same as current
No Changes Posted
Safety [ Time Frame: 12 months per patient ] [ Designated as safety issue: Yes ]
Evaluate safety of sorafenib in this patient population during 3 to 6 months period of use and and up to six months after completion of treatment.
Same as current
Not Provided
Not Provided
 
Pilot Study of Effect of Sorafenib on Portal Pressure
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.

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)

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Clinically Significant Portal Hypertension
  • Drug: Placebo
    Placebo Comparator: Placebo
  • Drug: Sorafenib
    Sorafenib, 400 mg twice daily
  • Placebo Comparator: Placebo
    Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.
    Intervention: Drug: Placebo
  • Experimental: Sorafenib
    Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.
    Intervention: Drug: Sorafenib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
44
August 2014
August 2013   (final data collection date for primary outcome measure)
  • 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
Both
20 Years to 75 Years
No
United States
 
NCT01714609
HIC # 1002006266
Yes
Guadalupe Garcia-Tsao, Yale University
Yale University
Onyx Therapeutics, Inc.
Principal Investigator: Guadalupe Garcia-Tsao, MD Yale University
Yale University
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP