Pilot Study of Effect of Sorafenib on Portal Pressure
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.
Clinically Significant Portal Hypertension
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|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|
- Change in HVPG from baseline [ Time Frame: Three Months ] [ Designated as safety issue: No ]Change in HVPG three months after initiation of sorafenib.
- 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.
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||August 2014|
|Estimated Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.
Placebo Comparator: Placebo
Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.
Sorafenib, 400 mg twice daily
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)
|United States, Connecticut|
|Yale Cancer Center||Recruiting|
|New Haven, Connecticut, United States, 06520|
|Contact: Guadalupe Garcia-Tsao, MD 203-737-6063 firstname.lastname@example.org|
|Sub-Investigator: Tamar Taddei, MD|
|Sub-Investigator: Howard S Hochster, MD|
|Sub-Investigator: Jill Lacy, MD|
|Sub-Investigator: Stacey Stein, MD|
|Sub-Investigator: Mario Strazzabosco, MD|
|Sub-Investigator: Jeffrey Pollak, MD|
|Principal Investigator: Guadalupe Garcia-Tsao, MD|
|United States, Texas|
|The University of Texas Health Science Center at Houston||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Michael Fallon, MD 713-500-6677 email@example.com|
|Principal Investigator: Michael B Fallon, MD|
|Principal Investigator:||Guadalupe Garcia-Tsao, MD||Yale University|