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

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ClinicalTrials.gov Identifier: NCT00571701
Recruitment Status : Completed
First Posted : December 12, 2007
Results First Posted : February 23, 2017
Last Update Posted : May 15, 2017
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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Recurrent Respiratory Papillomatosis
Interventions Drug: celebrex (celecoxib)
Drug: placebo
Enrollment 50
Recruitment Details Patients were recruited from 7 participating sites throughout the U.S. (locations in NY, VA, SD, AL, CA, IA and TN) that had investigators experienced in the treatment of this disease.
Pre-assignment Details Patients initially entered a 6 month pre-treatment observation period prior to randomization into the 2 treatment arms. 9 subjects did not start the treatment period and are therefore not included in demographics or the results sections.
Arm/Group Title Celecoxib First (12 Months), Then Placebo (12 Months) Placebo First (12 Months), Then Celecoxib (12 Months)
Hide Arm/Group Description

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

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

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.

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

Period Title: First Intervention 12 Months
Started 19 22
Completed 16 21
Not Completed 3 1
Reason Not Completed
Withdrawal by Subject             2             1
Death             1             0
Period Title: Second Intervention 12 Months
Started 16 21
Completed 13 20
Not Completed 3 1
Reason Not Completed
Adverse Event             0             1
Withdrawal by Subject             3             0
Arm/Group Title Celecoxib First, Then Placebo Placebo First, Then Celecoxib Total
Hide Arm/Group Description

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

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

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.

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

Total of all reporting groups
Overall Number of Baseline Participants 19 22 41
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants 22 participants 41 participants
Age < 20 9 11 20
Age 20 - < 40 3 9 12
Age 40 and above 7 2 9
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 22 participants 41 participants
Female
9
  47.4%
16
  72.7%
25
  61.0%
Male
10
  52.6%
6
  27.3%
16
  39.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 22 participants 41 participants
Hispanic or Latino
3
  15.8%
4
  18.2%
7
  17.1%
Not Hispanic or Latino
16
  84.2%
18
  81.8%
34
  82.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 22 participants 41 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  10.5%
2
   9.1%
4
   9.8%
White
17
  89.5%
19
  86.4%
36
  87.8%
More than one race
0
   0.0%
1
   4.5%
1
   2.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Mean Percent Change in Papilloma Growth Rate at 12 Month Measurement Compared to Baseline
Hide Description 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.
Time Frame Baseline to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All patients in each arm who completed the first 1 year treatment period. This is not a traditional cross-over study because we expected a sustained effect therefore no efficacy studies were done in segment C.
Arm/Group Title Celecoxib First, Then Placebo Placebo First, Then Celecoxib
Hide Arm/Group Description:

Patients randomized to start celecoxib. 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

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

Patients randomized to start placebo. 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.

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

Overall Number of Participants Analyzed 16 21
Mean (Standard Deviation)
Unit of Measure: percent change in mean growth rate
-5.4  (50.0) -15.2  (67.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Celecoxib First, Then Placebo, Placebo First, Then Celecoxib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Secondary Outcome
Title Percent of Patients With Positive Response to Treatment
Hide Description Percent of patients with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline
Time Frame Baseline to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All patients that completed first treatment period. This is not a traditional cross-over study because we expected a sustained effect therefore no efficacy studies were done in segment C.
Arm/Group Title Celecoxib First (12 Months), Then Placebo (12 Months) Placebo First (12 Months), Then Celecoxib (12 Months)
Hide Arm/Group Description:

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

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

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.

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

Overall Number of Participants Analyzed 16 21
Measure Type: Number
Unit of Measure: percent responders
12.5 28.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Celecoxib First (12 Months), Then Placebo (12 Months), Placebo First (12 Months), Then Celecoxib (12 Months)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.43
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Effect of Gender on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%.
Hide Description 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
Time Frame Baseline to12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who completed first treatment period. This is not a traditional cross-over study because we expected a sustained effect therefore no efficacy studies were done in segment C.
Arm/Group Title Celecoxib First - Males Placebo First- Males Celecoxib First- Females Placebo First- Females
Hide Arm/Group Description:
Males treated with celecoxib during the first treatment period
Males treated with placebo during the first treatment period
Females treated with celecoxib during the first treatment period
Females treated with placebo during the first treatment period
Overall Number of Participants Analyzed 8 15 8 6
Measure Type: Number
Unit of Measure: percent responders
12.50 40.00 12.50 0.00
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Celecoxib First - Males, Placebo First- Males, Celecoxib First- Females, Placebo First- Females
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.3
Comments Adjusted for multiple comparisons
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Effect of Juvenile Versus Adult Disease Onset on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%.
Hide Description 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.
Time Frame Baseline to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis conducted on all patients who completed first treatment period. Juvenile onset is defined as <18 years of age at time of diagnosis. Age of disease onset for 2 patients was not available. This is not a traditional cross-over study because we expected a sustained effect therefore no efficacy studies were done in segment C.
Arm/Group Title Celecoxib First- Juvenile Onset Placebo First- Juvenile-onsent Celecoxib First - Adult Onset Placebo First- Adult-onset
Hide Arm/Group Description:
Juvenile-onset subjects treated with celecoxib during the first treatment period
Juvenile-onset subjects treated with placebo during first treatment period
Adult-onset subjects treated with celecoxib during the first treatment period
Adult-onset subjects treated with placebo during the first treatment
Overall Number of Participants Analyzed 8 13 8 6
Measure Type: Number
Unit of Measure: percentage of responders
12.50 7.69 12.50 33.33
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Celecoxib First- Juvenile Onset, Placebo First- Juvenile-onsent, Celecoxib First - Adult Onset, Placebo First- Adult-onset
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments Adjusted for multiple comparisons
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Effect of HPV 6 Versus HPV 11 on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%
Hide Description 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.
Time Frame Baseline to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis conducted on all patients with HPV 6 or 11 infection who completed first treatment period. One patient with both HPV 6 and 11 and one patient with neither 6 or 11 were excluded. This is not a traditional cross-over study because we expected a sustained effect therefore no efficacy studies were done in segment C.
Arm/Group Title Celecoxib First - HPV 6 Placebo First- HPV 6 Celecoxib First- HPV 11 Placebo First- HPV 11
Hide Arm/Group Description:
Subjects infected with HPV 6 treated with celecoxib during the first treatment period
Subjects infected with HPV 6 treated with placebo during first treatment period
Subjects infected with HPV 11 treated with celecoxib during the first treatment period
Subjects infected with HPV 11 treated with placebo during the first treatment period
Overall Number of Participants Analyzed 11 14 4 5
Measure Type: Number
Unit of Measure: percent of responders
9.09 42.86 25.00 0.00
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Celecoxib First - HPV 6, Placebo First- HPV 6, Celecoxib First- HPV 11, Placebo First- HPV 11
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value > 0.5
Comments Adjusted for multiple comparisons
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Correlation Between Mean Plasma Level of Celecoxib and Response.
Hide Description 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.
Time Frame Baseline to 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who were randomized to receive celecoxib first and completed the first treatment period. This is not a traditional cross-over study because we expected a sustained effect therefore no efficacy studies were done in segment C.
Arm/Group Title Responders Non-responders
Hide Arm/Group Description:
Subjects randomized to celecoxib first with response greater than 50% at end of first treatment period relative to mean disease severity prior to treatment.
Subjects randomized to celecoxib first with response less than 50% at end of first treatment period relative to mean disease severity prior to treatment.
Overall Number of Participants Analyzed 2 14
Mean (Full Range)
Unit of Measure: pg. celecoxib/ml. plasma
151.3
(126.6 to 176.00)
543.41
(10.00 to 2422.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Responders, Non-responders
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.56
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
7.Secondary Outcome
Title Maintenance of Response Following Discontinuation of Celecoxib
Hide Description 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.
Time Frame End of first treatment period (month 12) to end of second treatment period (month 24)
Hide Outcome Measure Data
Hide Analysis Population Description
All patients with complete response to celecoxib in first treatment period who completed the second treatment period where they received placebo. Because the number of responders was so small, no statistical analysis was performed.
Arm/Group Title Celecoxib Responders-maintained Celecoxib Responders- Not Maintained
Hide Arm/Group Description:
Subjects randomized to celecoxib first with response greater than 50% at end of first treatment period that maintained response at end of second treatment.
Subjects randomized to celecoxib first with response greater than 50% at end of first treatment period whose papilloma growth rate worsened by more than 0.01 at end of second treatment period.
Overall Number of Participants Analyzed 2 0
Measure Type: Number
Unit of Measure: percent of patients
100
Time Frame AE reporting included all subjects who received at least three doses of study intervention. AE reporting was done throughout the entire 2 year period after randomization and also included up to approximately 30 days after the last dose of study drug was taken.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Celecoxib Placebo
Hide Arm/Group Description Patients who received celecoxib for 12 months during either time period Patients who received placebo for 12 months during either time period
All-Cause Mortality
Celecoxib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Celecoxib Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/40 (7.50%)      2/39 (5.13%)    
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
palpable lymph node * [1]  1/40 (2.50%)  0/39 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
death * 1 [2]  1/40 (2.50%)  1 0/39 (0.00%)  0
pneumonia * [3]  2/40 (5.00%)  1/39 (2.56%) 
influenza * [4]  0/40 (0.00%)  1/39 (2.56%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.0)
[1]
Patient with long-history of pulmonary RRP found to have palpable lymph node- needle biopsy revealed atypical findings and additional findings confirmed metastatic RRP associated lung cancer
[2]
Patient withdrew during 1st study period, died of pulmonary pneumonia secondary to RRP associated lung cancer 3 months after her last dose of study drug
[3]
pneumonia resulting in inpatient hospitalization, 2 subjects had known pulmonary RRP and third patient had a tracheotomy
[4]
Resulted in inpatient hospitalization for this patient due to dehydration secondary to diarrhea and vomiting as a result of the influenza
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Celecoxib Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/40 (40.00%)      18/39 (46.15%)    
Gastrointestinal disorders     
abdominal pain * [1]  4/40 (10.00%)  5/39 (12.82%) 
nausea or vomiting *  2/40 (5.00%)  5/39 (12.82%) 
diarrhea *  4/40 (10.00%)  3/39 (7.69%) 
General disorders     
pyrexia * [2]  2/40 (5.00%)  5/39 (12.82%) 
Respiratory, thoracic and mediastinal disorders     
non-cardiac chest discomfort * [3]  4/40 (10.00%)  4/39 (10.26%) 
upper respiratory infection * [4]  7/40 (17.50%)  9/39 (23.08%) 
*
Indicates events were collected by non-systematic assessment
[1]
Includes AEs reported as abdominal discomfort, abdominal pain, abdominal pain upper, dyspepsia, flatulence, gastritis and stomach infection
[2]
elevated temperature
[3]
AE term includes cough, chest discomfort
[4]
AE terms include increased nasal secretions, rhinitis, strep infection, croup and sinusitis
Rare prevalence of moderate to severe recurrent respiratory papillomatosis (estimated at 1:1million) limited enrollment
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Bettie Steinberg
Organization: Northwell Health (previously known as NorthShore-LIJ Health System)
Phone: 516-562-1159
EMail: bsteinbe@northwell.edu
Layout table for additonal information
Responsible Party: Northwell Health
ClinicalTrials.gov Identifier: NCT00571701     History of Changes
Obsolete Identifiers: NCT00297999
Other Study ID Numbers: 1U01DC007946-01A2 ( U.S. NIH Grant/Contract )
1U01DC007946-01A2 ( U.S. NIH Grant/Contract )
First Submitted: December 10, 2007
First Posted: December 12, 2007
Results First Submitted: August 9, 2016
Results First Posted: February 23, 2017
Last Update Posted: May 15, 2017