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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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 Chicag
Sponsor: University of Chicago

Current Primary Outcome: Monthly 6MW/B [ Time Frame: 16 weeks ]

Original Primary Outcome:

  • Monthly 6MW/B
  • WHO functional class
  • 4 month right heart catheterization


Current Secondary Outcome:

  • Efficacy [ Time Frame: 16 Weeks ]
  • World Health Organization (WHO) function class [ Time Frame: 16 weeks ]
  • Right heart catheterization [ Time Frame: 16 Week ]
  • Naughton Balke-Treadmill Test [ Time Frame: 16 Weeks ]


Original Secondary Outcome:

Information By: University of Chicago

Dates:
Date Received: March 26, 2007
Date Started: March 2007
Date Completion:
Last Updated: August 23, 2016
Last Verified: August 2016