Sorafenib for Hepatopulmonary Syndrome

NCT02021929 | Terminated Phase 2 Results DMC

• 2 other identifiers: 819185UM1HL116886
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 7

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.

Conditions

Hepatopulmonary Syndrome

Keywords

Randomized Controlled Trial; Clinical Trial; sorafenib; Hepatopulmonary Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in Alveolar-arterial Oxygen Gradient Between Sorafenib and Placebo Groups

  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.

  Baseline to 12 weeks

Secondary Outcomes (2)

• Number of Participants With Improvement in Intrapulmonary Shunting From Baseline to 12 Weeks.

  Baseline to 12 weeks

• Change From Baseline in Percentage of Progenitor Cells (Peripheral Blood Mononuclear Cells or PBMCs)

  Baseline to 12 weeks

Study Arms (2)

Sorafenib

EXPERIMENTAL

400 mg (2 capsules) taken by mouth once a day

Drug: Sorafenib

Placebo

PLACEBO COMPARATOR

2 capsules taken by mouth once a day

Drug: Placebo

Interventions

Sorafenib DRUG

Sorafenib is a kinase inhibitor indicated for the treatment of: * Unresectable hepatocellular carcinoma * Advanced renal cell carcinoma * Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment

Also known as: Nexavar

Sorafenib

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of HPS:
• AaPO2 ≥ 15 mm Hg (≥ 20 mm Hg for age \> 64 yrs)
• Intrapulmonary shunting
• Absence of significant restriction (TLC \< 70%) or obstruction (FEV1 \< 80% \& FEV1/FVC \< 70%)
• 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.

You may not qualify if:

• 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:
• Active coronary artery disease
• 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:

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (7)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Columbia University-NewYork-Presbyterian Hospital

New York, New York, 10032, United States

Location

University of Pennsylvania - Perelman Center

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29424, United States

Location

University of Texas Health Science Center at Houston Medical School

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Hepatopulmonary Syndrome

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Recruitment difficult due to challenges in screening for HPS, lack of patient awareness of HPS, and hesitation from potential subjects due to sorafenib side effects. Sample size reduced and sponsor terminated trial before reaching target sample size

Results Point of Contact

• Title: Dr. Steven Kawut
• Organization: University of Pennsylvania

kawut@upenn.edu

215-573-0258

Study Officials

• Steven M Kawut, MD, MS

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2013
• First Posted: December 27, 2013
• Study Start: March 1, 2014
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: April 25, 2019
• Results First Posted: April 25, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share

Locations

US (7)