| ID | Type | Description | Link |
|---|---|---|---|
| 1U01DC007946-01A2 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Deafness and Other Communication Disorders (NIDCD) | NIH |
| University of Iowa | OTHER |
| Eastern Virginia Medical School | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Baseline to 12 months |
| Effect of Gender on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%. |
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Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Bettie M Steinberg, PhD | Long Island Jewish Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama Birmingham | Birmingham | Alabama | 35294 | United States | ||
| UCSF Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16144915 | Background | 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. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Celecoxib First (12 Months), Then Placebo (12 Months) | 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 |
| FG001 | Placebo First (12 Months), Then Celecoxib (12 Months) | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention 12 Months |
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| |||||||||||||||||||||
| Second Intervention 12 Months |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 celebrex (celecoxib): Adults: 400 mg daily Pediatrics: 100 mg daily for weight between 12-25 kg or 200 mg daily for weight >25 kg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Mean | Standard Deviation | percent change in mean growth rate | Baseline to 12 months |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Celecoxib | Patients who received celecoxib for 12 months during either time period |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| death | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Non-systematic Assessment | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| abdominal pain | Gastrointestinal disorders | Non-systematic Assessment | Includes AEs reported as abdominal discomfort, abdominal pain, abdominal pain upper, dyspepsia, flatulence, gastritis and stomach infection |
Rare prevalence of moderate to severe recurrent respiratory papillomatosis (estimated at 1:1million) limited enrollment
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Bettie Steinberg | Northwell Health (previously known as NorthShore-LIJ Health System) | 516-562-1159 | bsteinbe@northwell.edu |
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| ID | Term |
|---|---|
| C535297 | Recurrent respiratory papillomatosis |
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| ID | Term |
|---|---|
| D000068579 | Celecoxib |
| ID | Term |
|---|---|
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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| University of Alabama at Birmingham |
| OTHER |
| University of California, San Francisco | OTHER |
| Vanderbilt University | OTHER |
| Sanford Health | OTHER |
| Weill Medical College of Cornell University | OTHER |
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|
| placebo | Drug | similar appearing capsules containing inert ingredients |
|
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 |
| 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. | 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. | 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. | 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. | End of first treatment period (month 12) to end of second treatment period (month 24) |
| San Francisco |
| California |
| 94115 |
| United States |
| University of Iowa | Iowa City | Iowa | 52242 | United States |
| Long Island Jewish Medical Center | New Hyde Park | New York | 11040 | United States |
| Sanford Health /USD | Sioux Falls | South Dakota | 57104 | United States |
| Vanderbilt University | Nashville | Tennessee | 37232 | United States |
| Eastern Virginia Medical School | Norfolk | Virginia | 23507 | United States |
| NOT COMPLETED |
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|
| BG001 | 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. celebrex (celecoxib): Adults: 400 mg daily Pediatrics: 100 mg daily for weight between 12-25 kg or 200 mg daily for weight >25 kg |
| BG002 | Total | Total of all reporting groups |
| participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Placebo First, Then Celecoxib | 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 |
|
|
|
| Secondary | 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 | 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. | Posted | Number | percent responders | Baseline to 12 months |
|
|
|
|
| Secondary | 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 | 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. | Posted | Number | percent responders | Baseline to12 months |
|
|
|
|
| Secondary | 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. | 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. | Posted | Number | percentage of responders | Baseline to 12 months |
|
|
|
|
| Secondary | 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. | 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. | Posted | Number | percent of responders | Baseline to 12 months |
|
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|
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| Secondary | 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. | 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. | Posted | Mean | Full Range | pg. celecoxib/ml. plasma | Baseline to 12 months |
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| Secondary | 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. | 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. | Posted | Number | percent of patients | End of first treatment period (month 12) to end of second treatment period (month 24) |
|
|
|
| 3 |
| 40 |
| 16 |
| 40 |
| EG001 | Placebo | Patients who received placebo for 12 months during either time period | 2 | 39 | 18 | 39 |
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| pneumonia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | pneumonia resulting in inpatient hospitalization, 2 subjects had known pulmonary RRP and third patient had a tracheotomy |
|
| palpable lymph node | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment | 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 |
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| influenza | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Resulted in inpatient hospitalization for this patient due to dehydration secondary to diarrhea and vomiting as a result of the influenza |
|
|
| nausea or vomiting | Gastrointestinal disorders | Non-systematic Assessment |
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| non-cardiac chest discomfort | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | AE term includes cough, chest discomfort |
|
| upper respiratory infection | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | AE terms include increased nasal secretions, rhinitis, strep infection, croup and sinusitis |
|
| pyrexia | General disorders | Non-systematic Assessment | elevated temperature |
|
| diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
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| D001555 |
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |