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

NCT00571701 | Completed Phase 2 Results DMC

• 1 other identifier: 1U01DC007946-01A2
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 7

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.

Conditions

Recurrent Respiratory Papillomatosis

Keywords

HPV; RRP

Outcome Measures

Primary Outcomes (1)

• Mean Percent Change in Papilloma Growth Rate at 12 Month Measurement Compared to Baseline

  Change in mean growth rates during the last 3 months of the first treatment period compared to the mean values at baseline. Endoscopy and removal of all tumor was done every 3 months. Growth rate is calculated as the scored amount of papilloma recurrence in a 3 month period divided by the exact number of days since last endoscopy and removal of all tumor.

  Baseline to 12 months

Secondary Outcomes (6)

• Percent of Patients With Positive Response to Treatment

  Baseline to 12 months

• Effect of Gender on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%.

  Baseline to12 months

• Effect of Juvenile Versus Adult Disease Onset on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%.

  Baseline to 12 months

• Effect of HPV 6 Versus HPV 11 on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%

  Baseline to 12 months

• Correlation Between Mean Plasma Level of Celecoxib and Response.

  Baseline to 12 months

Study Arms (2)

celecoxib first, then placebo

ACTIVE COMPARATOR

Patients randomized to start celecoxib 6 months after enrollment. Then cross over to placebo after 1 year. Celecoxib dosing will be given orally 400mg once a day for adults, 200 mg once a day for pediatric patients between 12-25kg, 100mg once a day for pediatric patients \< 12kg

Drug: celebrex (celecoxib); Drug: placebo

Placebo first, then celecoxib

PLACEBO COMPARATOR

Patients randomized to start placebo 6 months after enrollment. One placebo capsule will be taken orally once a day. Placebo will match appearance of active celecoxib capsules. Cross over to 12 months of treatment with celecoxib after 1 year.

Drug: celebrex (celecoxib); Drug: placebo

Interventions

celebrex (celecoxib) DRUG

Adults: 400 mg celebrex (celecoxib) daily Pediatrics: 100 mg celebrex (celecoxib) daily for weight between 12-25 kg or 200 mg Celebrex (celecoxib) daily for weight \>25 kg

Also known as: Celebrex

Placebo first, then celecoxib; celecoxib first, then placebo

placebo DRUG

similar appearing capsules containing inert ingredients

Placebo first, then celecoxib; celecoxib first, then placebo

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwell Health: lead
• National Institute on Deafness and Other Communication Disorders (NIDCD): collaborator
• University of Iowa: collaborator
• Eastern Virginia Medical School: collaborator
• University of Alabama at Birmingham: collaborator
• University of California, San Francisco: collaborator
• Vanderbilt University: collaborator
• Sanford Health: collaborator
• Weill Medical College of Cornell University: collaborator

Study Sites (7)

University of Alabama Birmingham

Birmingham, Alabama, 35294, United States

Location

UCSF Medical Center

San Francisco, California, 94115, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

Sanford Health /USD

Sioux Falls, South Dakota, 57104, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23507, United States

Location

Related 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. doi: 10.1158/1078-0432.CCR-04-2664.

  PMID: 16144915 BACKGROUND

MeSH Terms

Conditions

Recurrent respiratory papillomatosis

Interventions

Celecoxib

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Rare prevalence of moderate to severe recurrent respiratory papillomatosis (estimated at 1:1million) limited enrollment

Results Point of Contact

• Title: Dr. Bettie Steinberg
• Organization: Northwell Health (previously known as NorthShore-LIJ Health System)

bsteinbe@northwell.edu

516-562-1159

Study Officials

• Bettie M Steinberg, PhD

  Long Island Jewish Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2007
• First Posted: December 12, 2007
• Study Start: February 1, 2008
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: May 15, 2017
• Results First Posted: February 23, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)