Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study has been completed.
Sponsor:
Collaborators:
National Institute on Deafness and Other Communication Disorders (NIDCD)
University of Iowa
Eastern Virginia Medical School
University of Alabama at Birmingham
University of California, San Francisco
Vanderbilt University
Sanford Health
Weill Medical College of Cornell University
Information provided by (Responsible Party):
Northwell Health
ClinicalTrials.gov Identifier:
NCT00571701
First received: December 10, 2007
Last updated: December 29, 2016
Last verified: December 2016
  Purpose
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.

Condition Intervention Phase
Recurrent Respiratory Papillomatosis
Drug: celebrex (celecoxib)
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentered Randomized Study of Celebrex (Celecoxib) in Patients With Recurrent Respiratory Papillomatosis

Resource links provided by NLM:


Further study details as provided by Northwell Health:

Primary Outcome Measures:
  • Mean Percent Change in Papilloma Growth Rate at 12 Month Measurement Compared to Baseline [ Time Frame: Baseline to 12 months ]
    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.


Secondary Outcome Measures:
  • Percent of Patients With Positive Response to Treatment [ Time Frame: Baseline to 12 months ]
    Percent of patients with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline

  • Effect of Gender on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%. [ Time Frame: Baseline to12 months ]
    Percent of patients of each gender with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline

  • Effect of Juvenile Versus Adult Disease Onset on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%. [ Time Frame: Baseline to 12 months ]
    Percent of juvenile versus adult onset patients with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline.

  • Effect of HPV 6 Versus HPV 11 on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50% [ Time Frame: Baseline to 12 months ]
    Percent of patients with HPV 6 versus patients with HPV 11 with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline.

  • Correlation Between Mean Plasma Level of Celecoxib and Response. [ Time Frame: Baseline to 12 months ]
    Mean plasma levels of celecoxib over months 3-12 in first treatment period correlated with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline.

  • Maintenance of Response Following Discontinuation of Celecoxib [ Time Frame: End of first treatment period (month 12) to end of second treatment period (month 24) ]
    Percent of patients who responded to celecoxib with increase in papilloma growth rate of no greater than 0.01 at end of second treatment period compared to growth rate at end of first treatment period.


Enrollment: 50
Study Start Date: February 2008
Study Completion Date: January 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: celecoxib first, then placebo
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)
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
Other Name: Celebrex
Drug: placebo
similar appearing capsules containing inert ingredients
Placebo Comparator: Placebo first, then celecoxib
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)
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
Other Name: Celebrex
Drug: placebo
similar appearing capsules containing inert ingredients

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

Ages Eligible for Study:   2 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00571701

Locations
United States, Alabama
University of Alabama Birmingham
Birmingham, Alabama, United States, 35294
United States, California
UCSF Medical Center
San Francisco, California, United States, 94115
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, New York
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
United States, South Dakota
Sanford Health /USD
Sioux Falls, South Dakota, United States, 57104
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Virginia
Eastern Virginia Medical School
Norfolk, Virginia, United States, 23507
Sponsors and Collaborators
Northwell Health
National Institute on Deafness and Other Communication Disorders (NIDCD)
University of Iowa
Eastern Virginia Medical School
University of Alabama at Birmingham
University of California, San Francisco
Vanderbilt University
Sanford Health
Weill Medical College of Cornell University
Investigators
Principal Investigator: Bettie M Steinberg, PhD Long Island Jewish Medical Center
  More Information

Publications:
Responsible Party: Northwell Health
ClinicalTrials.gov Identifier: NCT00571701     History of Changes
Obsolete Identifiers: NCT00297999
Other Study ID Numbers: 1U01DC007946-01A2 ( US NIH Grant/Contract Award Number )
Study First Received: December 10, 2007
Results First Received: August 9, 2016
Last Updated: December 29, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Northwell Health:
HPV
RRP

Additional relevant MeSH terms:
Papilloma
Respiratory Tract Infections
Papillomavirus Infections
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Infection
Respiratory Tract Diseases
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Celecoxib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 28, 2017