Study of Celebrex (Celecoxib) in Patients With Recurrent Respiratory Papillomatosis

• What is the efficacy of celebrex response relative to conventional endoscopy and surgical removal in reducing recurrence,and is improvement maintained when celecoxib therapy stops? [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  

• Do any clinical characteristics (age of onset, gender, HPV type) predict response? [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  
• Do molecular markers suggest inhibitions of COX-2 as mechanism of response? [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  
• Does celebrex reduce persistence of HPV DNA or alter HPV expression. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  

This is a randomized double blind placebo-controlled study,with plans to include 5 additional U.S. centers in the near future. The primary goal of this study is to determine whether celecoxib has efficacy in elimination or reduction of recurrent disease in patients with RRP. Our secondary goals are to determine whether continued celecoxib is required to maintain response, to correlate response with select patient demographics and persistence of latent HPV DNA, and to determine whether celecoxib is acting through inhibition of COX-2, in order to begin to determine mechanism of effects in vivo on RRP. The study design encompasses a 30-month period, which can be divided into three segments:

Segment A: This is a 6 month run-in period in which all patients are assessed by direct laryngoscopy/bronchoscopy for disease severity, to permit growth rate stabilization and confirm accuracy of training of participating physicians. Patients will be treated by conventional surgery at three months and six months after enrollment.

Segment B: Patients begin 12 months of 400mg(adults), 100 mg (pediatric weight between 12 and 25 kg)or 200 mg (pediatric weight > 25kg) celecoxib daily or placebo treatment in addition to surgical removal of all papillomas at each 3 month interval. This segment directly tests the hypothesis that celecoxib is an efficacious treatment for moderate to severe RRP and forms the basis for the primary statistical analyses.

Segment C: The primary purpose of this segment is to determine whether gains made during celecoxib therapy are maintained after it is discontinued, or whether celecoxib will need to be taken indefinitely. This will be determined by a 12 month period on placebo after cessation of celecoxib for the early treatment group.