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

Pulmonary Arterial Hypertension Clinical Trial

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

Status Completed

Clinical Trial 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).

Clinical Trial 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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

• NCT number: NCT00452218
• Study type: Interventional
• Source: University of Chicago
• Status: Completed
• Phase: Phase 1
• Start date: March 2007
• Completion date: May 2012