Sorafenib for Hepatopulmonary Syndrome

Phase 2

Terminated

Conditions: Hepatopulmonary Syndrome

Interventions: Drug: Placebo
Drug: Sorafenib

Registration Number: NCT02021929

Lead Sponsor: University of Pennsylvania

Brief Summary: The main purpose of this clinical trial is to determine the safety and effects of the study drug, sorafenib, in adults diagnosed with hepatopulmonary syndrome (HPS). The study will evaluate how well the drug is tolerated and its effect on the level of oxygen in the blood and the function of the lung vessels.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 28

Inclusion Criteria

Diagnosis of HPS:
1. AaPO2 ≥ 15 mm Hg (≥ 20 mm Hg for age > 64 yrs)
2. Intrapulmonary shunting
3. Absence of significant restriction (TLC < 70%) or obstruction (FEV1 < 80% & FEV1/FVC < 70%)
4. Presence of cirrhosis/hepatic fibrosis and/or portal hypertension
Child-Pugh class A or B liver disease
Platelet count ≥ 30 ×10e9 per liter
Hemoglobin ≥ 8.5 g per deciliter
International normalized ratio ≤ 2.3
Albumin ≥ 2.8 g per deciliter
Total bilirubin ≤ 5 mg per deciliter
Alanine aminotransferase and aspartate aminotransferase ≤ 5 times the upper limit of the normal range
Serum creatinine ≤ 1.5 times the upper limit of the normal range and not receiving dialysis
Negative pregnancy test (for women of childbearing potential) at both screening and baseline visits. Post-menopausal women (defined as no menses for one year) and surgically sterilized women are not required to undergo a pregnancy test.
Subjects (men and women) of childbearing potential must agree to use medically acceptable contraception beginning at the signing of the Informed Consent Form until at least 14 days after the last dose of study drug.
Age ≥ 21 years
Ability to provide informed consent

Exclusion Criteria

Recent chronic heavy alcohol consumption
Enrollment in a clinical trial or concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 28 days of screening visit
Current hepatic encephalopathy
Active infection
Diagnosis of portopulmonary hypertension
WHO Class IV functional status
Congenital long-QT syndrome
Subjects who have used strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, phenobarbital, St. John's Wort [Hypericum perforatum], dexamethasone at a dose of greater than 16 mg daily, or rifampin [rifampicin], and/or rifabutin) within 28 days before randomization
Subjects who are currently taking Coumadin®(warfarin)
Active or clinically significant cardiac disease, including:
1. Active coronary artery disease
2. Unstable angina (anginal symptoms at rest), new-onset angina within 12 weeks before randomization, or myocardial infarction within 24 weeks before randomization
Liver or other solid organ transplant recipients
Expectation of liver transplant within four months of randomization
Hepatocellular carcinoma that does not meet all of the following criteria:
1. Single lesion ≤ 3 cm documented by LIRADS criteria
2. Complete response to ablative therapy (TACE, RFA, alcohol ablation) using the modified RECIST criteria one month after therapy with no more than two treatments
3. No other lesions develop after initiation of HCC therapy
Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg on repeated measurement) despite optimal medical management.
Any hemorrhage/bleeding event of NCI-Common Toxicity Criteria for Adverse Effects v4.0 Grade 3 or higher within 4 weeks before randomization
Presence of a non-healing wound, non-healing ulcer, or bone fracture
Women who are pregnant or breast-feeding
Major surgery 28 days prior to randomization
Subjects with any previously untreated or concurrent cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization are allowed. All cancer treatments (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) must be completed at least 3 years prior to study entry (i.e., signature date of the informed consent form).
Inability to comply with the protocol and/or not willing or not available for follow-up assessments

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	2 capsules taken by mouth once a day
Sorafenib	Sorafenib	400 mg (2 capsules) taken by mouth once a day

Primary Outcome Measures

Name	Time	Method
Change in Alveolar-arterial Oxygen Gradient Between Sorafenib and Placebo Groups	Baseline to 12 weeks	Alveolar-arterial oxygen gradient is a calculated measure of oxygenation. It is the difference between the amount of the oxygen in the alveoli and the amount of oxygen in arterial blood. Calculation is based on values from an Arterial Blood Gas test. Difference in change in alveolar-arterial oxygen gradient between sorafenib and placebo from baseline to 12 weeks.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Percentage of Progenitor Cells (Peripheral Blood Mononuclear Cells or PBMCs)	Baseline to 12 weeks	Progenitor Cells (Peripheral Blood Mononuclear Cells or PBMCs) are obtained and measured from blood samples collected from each participant. Difference in change from baseline to 12 weeks in the Percentage of Progenitor Cells between sorafenib and placebo groups.
Number of Participants With Improvement in Intrapulmonary Shunting From Baseline to 12 Weeks.	Baseline to 12 weeks	Intrapulmonary shunting is measured based on results from a saline-bubble echo test. Number of participants with measured improvement in intrapulmonary shunting from baseline to 12 weeks in the sorafenib and placebo groups

Trial Locations

Locations (7): Northwestern University Feinberg School of Medicine
🇺🇸
Chicago, Illinois, United States
University of Texas Health Science Center at Houston Medical School
🇺🇸
Houston, Texas, United States
Mayo Clinic Arizona
🇺🇸
Phoenix, Arizona, United States
University of Pennsylvania - Perelman Center
🇺🇸
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Columbia University-NewYork-Presbyterian Hospital
🇺🇸
New York, New York, United States
Mayo Clinic - Rochester
🇺🇸
Rochester, Minnesota, United States