The Effect of Sorafenib on Portal Pressure

NCT ID: NCT01714609

Last Updated: 2020-12-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-31

Study Completion Date

2014-09-30

Brief Summary

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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

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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)

Conditions

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Clinically Significant Portal Hypertension

Keywords

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portal hypertension sorafenib

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo Comparator: Placebo

Sorafenib

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

Group Type EXPERIMENTAL

Sorafenib

Intervention Type DRUG

Sorafenib, 400 mg twice daily

Interventions

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Placebo

Placebo Comparator: Placebo

Intervention Type DRUG

Sorafenib

Sorafenib, 400 mg twice daily

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

20 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Onyx Therapeutics, Inc.

INDUSTRY

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Guadalupe Garcia-Tsao, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

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Yale Cancer Center

New Haven, Connecticut, United States

Site Status

VA Medical Center West Haven

West Haven, Connecticut, United States

Site Status

Brigham & Womens

Boston, Massachusetts, United States

Site Status

New York University Langone Medical Center

New York, New York, United States

Site Status

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, United States

Site Status

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

Countries

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United States

Other Identifiers

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1002006266

Identifier Type: -

Identifier Source: org_study_id