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Papilloma

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Recurrent Respiratory Papillomatosis

Anti-Inflammatory Agents

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All Drugs and Chemicals

Celecoxib

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

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

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.

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

celebrex (celecoxib)

similar appearing capsules containing inert ingredients

placebo

Bettie M Steinberg, PhD

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.

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

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

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 of patients with reduction in papilloma growth rate greater than 50% during the last 3 months of first treatment period compared to baseline

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 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.

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.

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.

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.

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

Northwell Health

Patients who received celecoxib for 12 months during either time period

Patients who received placebo for 12 months during either time period

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

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

Celecoxib First, Then 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.

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 First, Then Celecoxib

Total

Age < 20

Age 20 - < 40

Age 40 and above

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

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

Dr. Bettie Steinberg

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

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.

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

Celecoxib First (12 Months), Then Placebo (12 Months)

Placebo First (12 Months), Then Celecoxib (12 Months)

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.

Percent of Patients With Positive Response to Treatment

Males treated with celecoxib during the first treatment period

Celecoxib First - Males

Males treated with placebo during the first treatment period

Placebo First- Males

Females treated with celecoxib during the first treatment period

Celecoxib First- Females

Females treated with placebo during the first treatment period

Placebo First- Females

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.

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

Juvenile-onset subjects treated with celecoxib during the first treatment period

Celecoxib First- Juvenile Onset

Juvenile-onset subjects treated with placebo during first treatment period

Placebo First- Juvenile-onsent

Adult-onset subjects treated with celecoxib during the first treatment period

Celecoxib First - Adult Onset

Adult-onset subjects treated with placebo during the first treatment

Placebo First- Adult-onset

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.

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

Subjects infected with HPV 6 treated with celecoxib during the first treatment period

Celecoxib First - HPV 6

Subjects infected with HPV 6 treated with placebo during first treatment period

Placebo First- HPV 6

Subjects infected with HPV 11 treated with celecoxib during the first treatment period

Celecoxib First- HPV 11

Subjects infected with HPV 11 treated with placebo during the first treatment period

Placebo First- HPV 11

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.

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

Subjects randomized to celecoxib first with response greater than 50% at end of first treatment period relative to mean disease severity prior to treatment.

Responders

Subjects randomized to celecoxib first with response less than 50% at end of first treatment period relative to mean disease severity prior to treatment.

Non-responders

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.

Correlation Between Mean Plasma Level of Celecoxib and Response.

Subjects randomized to celecoxib first with response greater than 50% at end of first treatment period that maintained response at end of second treatment.

Celecoxib Responders-maintained

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.

Celecoxib Responders- Not Maintained

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Celebrex (Celecoxib) in Patients With Recurrent Respiratory Papillomatosis	NCT00571701	Recurrent Respi...	celebrex (celec... placebo	2 Years -	Northwell Health
Study of Celebrex (Celecoxib) in Patients With Recurrent Respiratory Papillomatosis	NCT00571701	Recurrent Respi...	celebrex (celec... placebo	2 Years -	Northwell Health

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