Clinical trial NCT02021929: Sorafenib for Hepatopulmonary Syndrome
Official title: Sorafenib in Patients With Hepatopulmonary Syndrome: A Double-Blind Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hepatopulmonary Syndrome
Keywords: Randomized Controlled Trial
Clinical Trial
sorafenib
Hepatopulmonary Syndrome
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2013-12-27
Enrollment: 28
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Alveolar-arterial Oxygen Gradient Between Sorafenib and Placebo Groups
timeFrame: Baseline to 12 weeks
Secondary outcomes:
measure: Number of Participants With Improvement in Intrapulmonary Shunting From Baseline to 12 Weeks.
timeFrame: Baseline to 12 weeks
measure: Change From Baseline in Percentage of Progenitor Cells (Peripheral Blood Mononuclear Cells or PBMCs)
timeFrame: Baseline to 12 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: New York
country: United States
facility: Columbia University-NewYork-Presbyterian Hospital
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania - Perelman Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston Medical School
state: Texas
Study officials:
affiliation: University of Pennsylvania
name: Steven M Kawut, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: