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
  Purpose

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.


Condition Intervention Phase
Clinically Significant Portal Hypertension
Drug: Placebo
Drug: Sorafenib
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Change in HVPG from baseline [ Time Frame: Three Months ] [ Designated as safety issue: No ]
    Change in HVPG three months after initiation of sorafenib.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 44
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)
Arms Assigned Interventions
Placebo Comparator: Placebo
Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.
Drug: Placebo
Placebo Comparator: Placebo
Experimental: Sorafenib
Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.
Drug: Sorafenib
Sorafenib, 400 mg twice daily

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

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01714609

Locations
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06520
Contact: Guadalupe Garcia-Tsao, MD    203-737-6063    guadalupe.garcia-tsao@yale.edu   
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    michael.b.fallon@uth.tmc.edu   
Principal Investigator: Michael B Fallon, MD         
Sponsors and Collaborators
Yale University
Onyx Therapeutics, Inc.
Investigators
Principal Investigator: Guadalupe Garcia-Tsao, MD Yale University
  More Information

No publications provided

Responsible Party: Guadalupe Garcia-Tsao, Principal Investigator, Yale University
ClinicalTrials.gov Identifier: NCT01714609     History of Changes
Other Study ID Numbers: HIC # 1002006266
Study First Received: October 23, 2012
Last Updated: October 23, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Yale University:
portal hypertension
sorafenib

Additional relevant MeSH terms:
Hypertension
Hypertension, Portal
Carcinoma, Hepatocellular
Vascular Diseases
Cardiovascular Diseases
Liver Diseases
Digestive System Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014