Celebrex (Celecoxib) Treatment of Laryngeal Papilloma

• Sponsor: Boston University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00592319
• Collaborator: National Institute on Deafness and Other Communication Disorders (NIDCD) (NIH)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 50
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Laryngeal Papilloma	Drug: Celebrex; Device: PDL; Procedure: CO2 laser or microsurgery	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Voice-preserving Treatment of Laryngeal Papilloma
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PDL+Celebrex 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; oral taking of Celebrex (100 mg, BID) for 9 months; Other Names: Celecoxib ; Device: PDL; once time radiation on laryngeal papilloma with PDL , at 6.0-8.0 J; Other Names: 585 nm PDL (cynosure Inc. Mass)
Active Comparator: standard surgery 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; once-time surgery to remove laryngeal papilloma; Other Names: ablation laser or micro-instrumental surgery

Outcome Measures

Primary Outcome Measures

1. Number of Case With Papilloma Recurrence During a 12-month Follow up [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.

Secondary Outcome Measures

1. Time Course (Month) With Papilloma Recurrence During 12-month Follow up [12 months]

   The measuer is reported as time course (i.e., how many month) to see papilloma recurrence if there is any such recurrence.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 18 to 64 years of age

2. with laryngeal papillomas requiring surgical treatment

3. willingness to participate in the study

4. a signed informed consent form

Exclusion Criteria:

1. age less than 18 years

2. evidence of mental impairment so that the patient can not understand or sign the consent form

3. malignant diseases such as laryngeal cancer

4. established coronary heart and artery disorder, cerebrovascular disease, and other cardiovascular diseases

5. 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

6. hypertension, with ongoing blood pressure > 150 mg Hg systolic or to require medication

7. family history with serious cardiovascular events and problems

8. any sign and evidence which in the opinion of cardiovascular physician warrants exclusion of subject

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston Medical Center	Boston	Massachusetts	United States	02118

Sponsors and Collaborators

• Boston University
• National Institute on Deafness and Other Communication Disorders (NIDCD)

Investigators

• Principal Investigator: Wang Zhi, M.D, Boston Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Zhi Wang, Professor and Director, Boston University
• ClinicalTrials.gov Identifier: NCT00592319
• Other Study ID Numbers: RDC-006617A; R01DC006617
• First Posted: Jan 14, 2008
• Last Update Posted: Aug 31, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by Zhi Wang, Professor and Director, Boston University: Papilloma; pulsed dye laser; Celebrex; voice
• Additional relevant MeSH terms: Papilloma; Laryngeal Neoplasms; Celecoxib

Study Results

Participant Flow

Recruitment Details	3 years
Pre-assignment Detail	Many patients, who were eligible for this study, finally declined to participate this study due to a safety concern with Celebrex

Arm/Group Title	Control	Experimental
Arm/Group Description	once-time routine surgery with (either of CO2 laser at continue model and 10.0-20.0 W, or "cold" surgery with micro-instruments), in 15 subjects	once-time PDL surgery at 6.0-8.0 W, followed by oral taking of Celecoxib (100mg,BID)for 9 months
Period Title: Overall Study
STARTED	2	8
COMPLETED	2	5
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	Control	Experimental	Total
Arm/Group Description	treated with routine surgery (CO2 laser or "cold" microsurgery), in 15 cases	treated with once-time PDL, followed by oral taking of 9-month Celecoxib, in 15 cases	Total of all reporting groups
Overall Participants	2	8	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	8 100%	10 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 50%	4 50%	5 50%
Male	1 50%	4 50%	5 50%

Outcome Measures

1. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

12-month follow-up

Arm/Group Title	Control	Experiment
Arm/Group Description	treated with once-time routine surgery	treated with both of once-time PDL and 9-month Celebrex
Measure Participants	2	5
Mean (Full Range) [month]	3.5	5.2

2. Primary Outcome

Title	Number of Case With Papilloma Recurrence During a 12-month Follow up
Description	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.
Time Frame	12-month follow up

Outcome Measure Data

Analysis Population Description

The paticipants for analysis were those who had the recurrence or completed follow-up period. The analysis was per protocol, and follow-up period was 12 months.

Arm/Group Title	Control	Experienment
Arm/Group Description	treated with once-time routine surgery (CO2 laser or "cold" microsurgery)	treated with once-time PDL, followed by oral taking of Celebrex (100mg,BID) for 9 months
Measure Participants	2	5
Number [case]	2	5

Adverse Events

Time Frame	Primary: cardiovascular events for 12 months
Adverse Event Reporting Description	Others: laser and surgery complications for 12 months
Arm/Group Title	Experiment		Control
Arm/Group Description	treated with both of PDL and Celecoxib		treatd with CO2 laser or microsurgery
All Cause Mortality
	Experiment		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Experiment		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Experiment		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/2 (0%)

Limitations/Caveats

We failed to recruit a total of 30 cases, due to (1) This disease is relative less common in clinic; and (2) particularly, more and more of patients now had a serious concern in safety of Celebrex due to news and warnings to public in recent years.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.