Sorafenib Study: Dosing in Patients With Pulmonary Arterial Hypertension (PAH)

Phase 1

Completed

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Drug: Sorafenib

• Registration Number: NCT00452218
• Lead Sponsor: University of Chicago

Brief Summary

The purpose of this study is to assess the safety and tolerability of sorafenib in patients with PAH already on existing therapy with a prostacyclin \[epoprostenol (Flolan)\], treprostinil (Remodulin), or iloprost alone, or with or without sildenafil (Viagra/Revatio).

Detailed Description

Pulmonary arterial hypertension (PAH) is an angioproliferative vasculopathy resulting from abnormal endothelial and smooth muscle cell interactions. Idiopathic and familial PAH (formerly known as primary pulmonary hypertension) occurs more often in women than in men, with a median survival of 2.8 years if untreated and a mean age at diagnosis of 35 years. The key features of this vasculopathy causes a progressive narrowing of the pulmonary artery and their branches, resulting in right heart failure and death. Proliferating endothelial cells obliterate medium-sized precapillary arteries, thereby forming the characteristic "plexiform" lesions. When combined with the expansion of both vascular smooth muscle cells and adventitial cells in pulmonary arteries, these observations evoke comparisons to cancer pathobiology. Currently, FDA-approved therapies for PAH such as prostacyclins (epoprostenol, treprostinil, and iloprost), endothelin receptor blockers (bosentan) and phosphodiesterase inhibitors (sildenafil) all produce functional improvement (6 minute walk distance- 6MW) with minimal change in hemodynamic measurements at cardiac catheterization. Only epoprostenol has provided survival benefit with the 5-year survival, remaining at 50% without demonstrable reversal of the vasculopathy. Clearly there is a critical need for novel targets and therapies for PAH.

In this protocol, the principal investigator (PI) will leverage a large PAH referral practice with an established clinical database to assess the potential utility of kinase inhibitors as a new class of agents for protease-activated receptor (PAR). These drugs inhibit processes important to pathological blood vessel branching and growth and have been a focus for the internationally renowned University of Chicago Phase I/II trials unit in oncology led by Dr. Mark Ratain (Co-Investigator). The University of Chicago has had a major role in the drug development of the recently (12/05) FDA-approved drug, sorafenib, for advanced renal carcinoma. Sorafenib inhibits Raf-1 kinase, a regulator of endothelial apoptosis, and inhibits angiogenesis growth factor receptors VEGFR-2, PDGFR-B, and VEGFR-3.

Study Timeline

• Study Start: 2007-03
• Study First Submitted: 2007-03-26
• Study First Submitted QC: 2007-03-26
• Study First Posted: 2007-03-27
• Primary Completion: 2012-05
• Study Completion: 2012-05
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-23
• Last Update Posted: 2016-08-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open	Sorafenib	-

Primary Outcome Measures

Name	Time	Method
Monthly 6MW/B	16 weeks

Secondary Outcome Measures

Name	Time	Method
Right heart catheterization	16 Week
Naughton Balke-Treadmill Test	16 Weeks
World Health Organization (WHO) function class	16 weeks
Efficacy	16 Weeks

Trial Locations

Locations (1)

The University of Chicago; 🇺🇸 Chicago, Illinois, United States