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

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

Official Title: A Multicentered Randomized Study of Celebrex (Celecoxib) in Patients With Recurrent Respiratory Papillomatosis

Brief Summary: This is a randomized double blind controlled study to determine if celebrex (celecoxib), a selective COX-2 inhibitor, can decrease the rate of recurrence in adult and pediatric patients with recurrent respiratory papillomatosis. All patients will be evaluated for disease severity at enrollment and at 3 month intervals for 30 months. After randomization, patients in the early treatment arm will begin celecoxib 6 months after enrollment. The delayed treatment arm will begin celecoxib 18 months after enrollment. All patients will receive celecoxib for 1 year. During the time that patients do not receive celecoxib, they will receive a placebo capsule with the same appearance. Follow-up visits will occur at three month intervals for the duration of the study.

Detailed Summary:

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 with plasma levels of celecoxib. 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. This is not a traditional cross-over study because we expected a sustained effect therefore no efficacy studies were done in segment C. However, the placebo first group wa
Sponsor: Northwell Health

Current Primary Outcome: Mean Percent Change in Papilloma Growth Rate at 12 Month Measurement Compared to Baseline [ Time Frame: Baseline to 12 months ]

Change in mean growth rates during the last 3 months of the first treatment period compared to the mean values at baseline. Endoscopy and removal of all tumor was done every 3 months. Growth rate is calculated as the scored amount of papilloma recurrence in a 3 month period divided by the exact number of days since last endoscopy and removal of all tumor.


Original Primary Outcome: 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 ]

Current Secondary Outcome:

  • Percent of Patients With Positive Response to Treatment [ Time Frame: Baseline to 12 months ]
    Percent of patients with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline
  • Effect of Gender on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%. [ Time Frame: Baseline to12 months ]
    Percent of patients of each gender with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline
  • Effect of Juvenile Versus Adult Disease Onset on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%. [ Time Frame: Baseline to 12 months ]
    Percent of juvenile versus adult onset patients with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline.
  • Effect of HPV 6 Versus HPV 11 on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50% [ Time Frame: Baseline to 12 months ]
    Percent of patients with HPV 6 versus patients with HPV 11 with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline.
  • Correlation Between Mean Plasma Level of Celecoxib and Response. [ Time Frame: Baseline to 12 months ]
    Mean plasma levels of celecoxib over months 3-12 in first treatment period correlated with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline.
  • Maintenance of Response Following Discontinuation of Celecoxib [ Time Frame: End of first treatment period (month 12) to end of second treatment period (month 24) ]
    Percent of patients who responded to celecoxib with increase in papilloma growth rate of no greater than 0.01 at end of second treatment period compared to growth rate at end of first treatment period.


Original Secondary Outcome:

  • Do any clinical characteristics (age of onset, gender, HPV type) predict response? [ Time Frame: 24 months ]
  • Do molecular markers suggest inhibitions of COX-2 as mechanism of response? [ Time Frame: 24 months ]
  • Does celebrex reduce persistence of HPV DNA or alter HPV expression. [ Time Frame: 24 months ]


Information By: Northwell Health

Dates:
Date Received: December 10, 2007
Date Started: February 2008
Date Completion:
Last Updated: March 31, 2017
Last Verified: March 2017