Clinical trial NCT00571701: Study of Celebrex (Celecoxib) in Patients With Recurrent Respiratory Papillomatosis
Official title: A Multicentered Randomized Study of Celebrex (Celecoxib) in Patients With Recurrent Respiratory Papillomatosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Respiratory Papillomatosis
Keywords: HPV
RRP
Lead sponsor: Northwell Health
Sponsor class: OTHER
Collaborators: name: National Institute on Deafness and Other Communication Disorders (NIDCD)
name: University of Iowa
name: Eastern Virginia Medical School
name: University of Alabama at Birmingham
name: University of California, San Francisco
name: Vanderbilt University
name: Sanford Health
name: Weill Medical College of Cornell University
First posted: 2007-12-12
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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 description: 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 was given celecoxib so that they could gain any possible benefits equivalent to those that received the celecoxib first.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Percent Change in Papilloma Growth Rate at 12 Month Measurement Compared to Baseline
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Percent of Patients With Positive Response to Treatment
timeFrame: Baseline to 12 months
measure: Effect of Gender on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%.
timeFrame: Baseline to12 months
measure: Effect of Juvenile Versus Adult Disease Onset on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%.
timeFrame: Baseline to 12 months
measure: Effect of HPV 6 Versus HPV 11 on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%
timeFrame: Baseline to 12 months
measure: Correlation Between Mean Plasma Level of Celecoxib and Response.
timeFrame: Baseline to 12 months
measure: Maintenance of Response Following Discontinuation of Celecoxib
timeFrame: End of first treatment period (month 12) to end of second treatment period (month 24)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: Sioux Falls
country: United States
facility: Sanford Health /USD
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
Study officials:
affiliation: Long Island Jewish Medical Center
name: Bettie M Steinberg, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu R, Abramson AL, Shikowitz MJ, Dannenberg AJ, Steinberg BM. Epidermal growth factor-induced cyclooxygenase-2 expression is mediated through phosphatidylinositol-3 kinase, not mitogen-activated protein/extracellular signal-regulated kinase kinase, in recurrent respiratory papillomas. Clin Cancer Res. 2005 Sep 1;11(17):6155-61. doi: 10.1158/1078-0432.CCR-04-2664.