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The Effect of Sorafenib on Portal Pressure

Primary Purpose

Clinically Significant Portal Hypertension

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Placebo

Sorafenib

About this trial

This is an interventional treatment trial for Clinically Significant Portal Hypertension focused on measuring portal hypertension, sorafenib

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Yale Cancer Center
VA Medical Center West Haven
Brigham & Womens
New York University Langone Medical Center
University of Pennsylvania School of Medicine
The University of Texas Health Science Center at Houston

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Sorafenib

Arm Description

Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.

Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.

Outcomes

Primary Outcome Measures

Patients With Change in HVPG From Baseline

Number of participants with a decrease in HPVG that was > 10% of baseline

Secondary Outcome Measures

Full Information

NCT ID

NCT01714609

First Posted

October 23, 2012

Last Updated

December 2, 2020

Sponsor

Yale University

Collaborators

Onyx Therapeutics, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01714609

Brief Title

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

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

August 2011 (undefined)

Primary Completion Date

September 2013 (Actual)

Study Completion Date

September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yale University

Collaborators

Onyx Therapeutics, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Clinically Significant Portal Hypertension

Keywords

portal hypertension, sorafenib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Subjects randomized to placebo will take two tablets of placebo by mouth twice daily.

Arm Title

Sorafenib

Arm Type

Experimental

Arm Description

Subjects randomized to Sorafenib will take Sorafenib 400 mg by mouth twice daily.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo Comparator: Placebo

Intervention Type

Drug

Intervention Name(s)

Sorafenib

Intervention Description

Sorafenib, 400 mg twice daily

Primary Outcome Measure Information:

Title

Patients With Change in HVPG From Baseline

Description

Number of participants with a decrease in HPVG that was > 10% of baseline

Time Frame

Three Months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Guadalupe Garcia-Tsao, MD

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Yale Cancer Center

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Facility Name

VA Medical Center West Haven

City

West Haven

State/Province

Connecticut

ZIP/Postal Code

06516

Country

United States

Facility Name

Brigham & Womens

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

New York University Langone Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

University of Pennsylvania School of Medicine

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

The University of Texas Health Science Center at Houston

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

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The Effect of Sorafenib on Portal Pressure

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