Celebrex (Celecoxib) Treatment of Laryngeal Papilloma

Study Overview
=================
Brief Summary
-----------------
Respiratory recurrent papilloma (RRP) is one of the most common benign tumors. Surgical removal is the current management for RRP, but it is a very traumatic procedure, and often leads to permanent voice dysfunction. In this study, we will develop a new, combined RRP treatment with a pulsed dye laser (PDL) and Celebrex. We will determine if Celebrex, a newly developed inhibitor of cyclooxygenase (COX)-2, can provide a long-term inhibitory effect on RRP, therefore preventing RRP from recurring. This combined strategy, if successful in this proposed study, will provide a new and ideal voice-preserving therapy for RRP that will deliver long-term efficacy in managing RRP.

Detailed Description
-----------------
RRP and its surgeries usually involves the vocal cords or other regions of the larynx, thereby, resulting in a poor voice. Our previous studies have shown the efficacy and safety of a microvascular targeting technique (MVT) for RRP treatment using the 585 nm PDL. This technique provides a less traumatic alternative to surgery. However, postoperative recurrence of lesions still remains a problem because of microvascular regrowth. This study is a continuation of our effort to develop a new and less traumatic treatment for RRP. In this study, we will develop a new, combined RRP treatment with PDL and Celebrex. We will determine if Celebrex, a newly developed inhibitor of COX-2, can provide a long-term inhibitory effect on RRP through its anti-angiogenic activity and the synergic effect produced with the laser therapy. The hypothesis is that postoperative administration of Celebrex will provide a long-term inhibitory effect on microvascular regrowth and on COX-2 enzyme, thereby, preventing RRP from recurring after the PDL therapy. Our specific aim in this study is to determine the synergic effect between PDL and Celebrex and long-term efficacy of Celecoxib in preventing postoperative RRP recurrence. We will compare this new combined strategy with traditional treatments in 30 adult patients. This is the first time to combined this new laser MVT technique with a COX-2 inhibitor for microvascular targeting therapy of RRP. This combined strategy, if successful in this proposed study, will provide a new and ideal voice-preserving therapy for RRP that will deliver long-term efficacy in managing RRP and will be safe and convenient enough for use in out-patient treatment.

Official Title
-----------------
Voice-preserving Treatment of Laryngeal Papilloma

Conditions
-----------------
Laryngeal Papilloma

Intervention / Treatment
-----------------
* Drug: Celebrex
* Device: PDL
* Procedure: CO2 laser or microsurgery


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 to 64 years of age with laryngeal papillomas requiring surgical treatment willingness to participate in the study a signed informed consent form Exclusion Criteria: age less than 18 years evidence of mental impairment so that the patient can not understand or sign the consent form malignant diseases such as laryngeal cancer established coronary heart and artery disorder, cerebrovascular disease, and other cardiovascular diseases established diabetes, which requires (1) insulin treatment; or (2) more than 2 oral agents of medication; or (3) to have a baseline HgbA1c >8.0 hypertension, with ongoing blood pressure > 150 mg Hg systolic or to require medication family history with serious cardiovascular events and problems any sign and evidence which in the opinion of cardiovascular physician warrants exclusion of subject

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PDL+Celebrex<br>endoscopic treatment with once-time PDL radiation at 6.0-8.0 J on laryngeal papilloma, followed by oral taking of 9-month Celebrex (100mg, BID), in 15 subjects | Drug: Celebrex<br>* oral taking of Celebrex (100 mg, BID) for 9 months<br>* Other names: Celecoxib;Device: PDL<br>* once time radiation on laryngeal papilloma with PDL , at 6.0-8.0 J<br>* Other names: 585 nm PDL (cynosure Inc. Mass);|
| Active Comparator: standard surgery<br>once-time and routine surgery, with either of carbon dioxide (CO2) laser radiation at 10.0-20.0 W or cold surgery with microinstruments, in 15 subjects | Procedure: CO2 laser or microsurgery<br>* once-time surgery to remove laryngeal papilloma<br>* Other names: ablation laser or micro-instrumental surgery;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Case With Papilloma Recurrence During a 12-month Follow up | Criteria for the recurrence: the site scoring >4, plus visible lesion found in >50% of the treated tissue area, after surgery Description: The caculation of the site scoring is based on a called Derkay's scoring system: to indicate how many anatomic site involved, from the 0 (the best)to 13 (the worst),among a total of 13 laryngeal sites such as epiglottis or right true vocal cords. | 12-month follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Course (Month) With Papilloma Recurrence During 12-month Follow up | The measuer is reported as time course (i.e., how many month) to see papilloma recurrence if there is any such recurrence. | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Papilloma, pulsed dye laser, Celebrex, voice