Sorafenib for Hepatopulmonary Syndrome (SHPS)

University of Pennsylvania

Status and phase

Terminated

Phase 2

Conditions

Hepatopulmonary Syndrome

Treatments

Drug: Placebo

Drug: Sorafenib

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT02021929

819185

UM1HL116886 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment

28 patients

Sex

All

Ages

21+ years old

Volunteers

No Healthy Volunteers

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