A Phase 2 interventional study of celebrex (celecoxib) and placebo in Recurrent Respiratory Papillomatosis, sponsored by Northwell Health. Completed at 7 sites in United States. Open to participants aged 2 Years and older. Per ClinicalTrials.gov, last updated 2017-05-15.
Sponsored by Northwell Health · Phase 2, Interventional, and Treatment
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.
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.
1,031 studies on the registry are indexed under Respiratory Tract Infections; 144 are open to participants now.
This study's enrollment of 50 is below the median of 199 across 698 interventional studies indexed under Respiratory Tract Infections.
Browse Respiratory Tract Infections studies →Northwell Health is the lead sponsor of 463 studies on the registry; 109 are open to participants now.
Of its 40 completed or terminated interventional studies of FDA-regulated products, 20 (50%) have results posted.
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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)
Exclusion Criteria:
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
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
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
similar appearing capsules containing inert ingredients
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.
Time frame: Baseline to 12 months
Percent of Patients With Positive Response to Treatment
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
Effect of Gender on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%.
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
Effect of Juvenile Versus Adult Disease Onset on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%.
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
Effect of HPV 6 Versus HPV 11 on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%
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
Correlation Between Mean Plasma Level of Celecoxib and Response.
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
Maintenance of Response Following Discontinuation of Celecoxib
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)
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.
| Milestone | Celecoxib First (12 Months), Then Placebo (12 Months) | Placebo First (12 Months), Then Celecoxib (12 Months) |
|---|---|---|
| Started | 19 | 22 |
| Completed | 16 | 21 |
| Not completed | 3 | 1 |
| Withdrew: Withdrawal by subject | 2 | 1 |
| Withdrew: Death | 1 | 0 |
| Milestone | Celecoxib First (12 Months), Then Placebo (12 Months) | Placebo First (12 Months), Then Celecoxib (12 Months) |
|---|---|---|
| Started | 16 | 21 |
| Completed | 13 | 20 |
| Not completed | 3 | 1 |
| Withdrew: Adverse event | 0 | 1 |
| Withdrew: Withdrawal by subject | 3 | 0 |
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.
| percent change in mean growth rate | Celecoxib First, Then Placebo | Placebo First, Then Celecoxib |
|---|---|---|
| Mean Percent Change in Papilloma Growth Rate at 12 Month Measurement Compared to Baseline | -5.4 ± 50.0 | -15.2 ± 67.3 |
Percent of patients with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline
| percent responders | Celecoxib First (12 Months), Then Placebo (12 Months) | Placebo First (12 Months), Then Celecoxib (12 Months) |
|---|---|---|
| Percent of Patients With Positive Response to Treatment | 12.5 | 28.6 |
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
| percent responders | Celecoxib First - Males | Placebo First- Males | Celecoxib First- Females | Placebo First- Females |
|---|---|---|---|---|
| Effect of Gender on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%. | 12.50 | 40.00 | 12.50 | 0.00 |
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.
| percentage of responders | Celecoxib First- Juvenile Onset | Placebo First- Juvenile-onsent | Celecoxib First - Adult Onset | Placebo First- Adult-onset |
|---|---|---|---|---|
| Effect of Juvenile Versus Adult Disease Onset on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%. | 12.50 | 7.69 | 12.50 | 33.33 |
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.
| percent of responders | Celecoxib First - HPV 6 | Placebo First- HPV 6 | Celecoxib First- HPV 11 | Placebo First- HPV 11 |
|---|---|---|---|---|
| Effect of HPV 6 Versus HPV 11 on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50% | 9.09 | 42.86 | 25.00 | 0.00 |
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.
| pg. celecoxib/ml. plasma | Responders | Non-responders |
|---|---|---|
| Correlation Between Mean Plasma Level of Celecoxib and Response. | 151.3 (126.6 to 176.00) | 543.41 (10.00 to 2422.50) |
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.
| percent of patients | Celecoxib Responders-maintained | Celecoxib Responders- Not Maintained |
|---|---|---|
| Maintenance of Response Following Discontinuation of Celecoxib | 100 | — |
Collected over 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.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Celecoxib | — | 3/40 (7.5%) | 16/40 (40%) |
| Placebo | — | 2/39 (5.1%) | 18/39 (46.2%) |
| Event | Celecoxib | Placebo |
|---|---|---|
| pneumoniaRespiratory, thoracic and mediastinal disorders | 2/40 | 1/39 |
| influenzaRespiratory, thoracic and mediastinal disorders | 0/40 | 1/39 |
| deathRespiratory, thoracic and mediastinal disorders | 1/40 | 0/39 |
| palpable lymph nodeNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/40 | 0/39 |
| Event | Celecoxib | Placebo |
|---|---|---|
| upper respiratory infectionRespiratory, thoracic and mediastinal disorders | 7/40 | 9/39 |
| abdominal painGastrointestinal disorders | 4/40 | 5/39 |
| nausea or vomitingGastrointestinal disorders | 2/40 | 5/39 |
| pyrexiaGeneral disorders | 2/40 | 5/39 |
| non-cardiac chest discomfortRespiratory, thoracic and mediastinal disorders | 4/40 | 4/39 |
| diarrheaGastrointestinal disorders | 4/40 | 3/39 |
| Age, Customized(participants) | Celecoxib First, Then Placebo | Placebo First, Then Celecoxib | Total |
|---|---|---|---|
| Age < 20 | 9 | 11 | 20 |
| Age 20 - < 40 | 3 | 9 | 12 |
| Age 40 and above | 7 | 2 | 9 |
| Sex: Female, Male(Participants) | Celecoxib First, Then Placebo | Placebo First, Then Celecoxib | Total |
|---|---|---|---|
| Female | 9 | 16 | 25 |
| Male | 10 | 6 | 16 |
| Ethnicity (NIH/OMB)(Participants) | Celecoxib First, Then Placebo | Placebo First, Then Celecoxib | Total |
|---|---|---|---|
| Hispanic or Latino | 3 | 4 | 7 |
| Not Hispanic or Latino | 16 | 18 | 34 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Celecoxib First, Then Placebo | Placebo First, Then Celecoxib | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 2 | 2 | 4 |
| White | 17 | 19 | 36 |
| More than one race | 0 | 1 | 1 |
| Unknown or Not Reported | 0 | 0 | 0 |
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