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

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 no 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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2012

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.

Intervention(s) in this Clinical Trial

• Drug: celebrex (celecoxib)
  • Adults: 400 mg daily Pediatrics: 100 mg daily for weight between 12-25 kg or 200 mg daily for weight >25 kg
• Drug: placebo capsules
  • Not relevant

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: early treatment
  • Patients randomized to start celecoxib 6 months after enrollment. Then cross over to placebo after 1 year.
• Placebo Comparator: delayed treatment
  • Patients randomized to start placebo 6 months after enrollment. Cross over to 12 months of treatment with celecoxib after 1 year.

Primary Measures

• 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
    Safety Issue?: No

Secondary Measures

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

Inclusion Criteria:

• Moderate to severe disease, defined as:
• Patients who have rapid regrowth of papillomas, requiring endoscopic removal at least 3 times within the past 12 months AND A papilloma growth rate from 0.03 to 0.06 (moderate) or >0.06 (severe) at time of initial direct endoscopy OR Having tracheal and/or bronchial or pulmonary papillomatosis (severe)
• Age > 2 years
• Gender- no restriction
• Race- no restriction

Exclusion Criteria:

• Fewer than 3 surgical procedures in previous year, without tracheal disease
• Age < 2 years
• Pregnancy, trying to become pregnant, breastfeeding or not willing to comply with birth control methods if sexually active female
• Serum creatinine > 1.5 X normal
• History of documented peptic ulcer disease or gastritis persisting despite treatment
• Abnormal liver function tests, as total bilirubin >1.5 X normal and SGOT > 3 X normal
• Allergy to NSAIDs, sulfa containing drugs or symptoms of Stevens-Johnson Syndrome
• Patients with connective tissue diseases such as SLE, Raynaud's or Systemic Sclerosis
• Patients with known diabetes
• Patients on warfarin, or on loop or thiazide diuretics
• Patients with a history of cardiovascular disease, myocardial infarct or stroke
• Patients with congestive heart failure
• Patients regularly taking > 81 mg of aspirin/day
• Patients with uncontrolled hypertension
• Patients with RRP associated malignancy currently receiving chemotherapy and/or radiation

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 2 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute on Deafness and Other Communication Disorders (NIDCD)

Overall Clinical Trial Officials and Contacts

Bettie M Steinberg, PhD Principal Investigator Long Island Jewish Medical Center  

Overall Contact: Ginny Mullooly, RN 718-470-7011 gmullool@lij.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00571701

Study ID Number: 1 U01 DC007946-01A2

ClinicalTrials.gov Identifier: NCT00571701

Health Authority: United States: Federal Government