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

Recurrent Respiratory Papillomatosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00571701
• Other study ID #: 1U01DC007946-01A2
• Secondary ID: U01DC007946NIH g
• Status: Completed
• Phase: Phase 2
• First received: December 10, 2007
• Last updated: May 13, 2015
• Start date: February 2008
• Est. completion date: January 2015

Study information

• Verified date: May 2015
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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 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.

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 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.

Other known NCT identifiers

• NCT00297999

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Papilloma
• Papillomavirus Infections
• Recurrent Respiratory Papillomatosis
• Respiratory Tract Infections

Intervention

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
• placebo capsules
Not relevant

Locations

Country	Name	City	State
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	University of Iowa	Iowa City	Iowa
United States	Vanderbilt University	Nashville	Tennessee
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	UCSF Medical Center	San Francisco	California
United States	Sanford Health /USD	Sioux Falls	South Dakota

Sponsors (2)

Lead Sponsor	Collaborator
Northwell Health	National Institute on Deafness and Other Communication Disorders (NIDCD)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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?		24 months	No
Secondary	Do any clinical characteristics (age of onset, gender, HPV type) predict response?		24 months	No
Secondary	Do molecular markers suggest inhibitions of COX-2 as mechanism of response?		24 months	No
Secondary	Does celebrex reduce persistence of HPV DNA or alter HPV expression.		24 months	No