Study of Celebrex (Celecoxib) in Patients With Recurrent Respiratory Papillomatosis
- Conditions
- Recurrent Respiratory Papillomatosis
- Interventions
- Drug: placebo
- Registration Number
- NCT00571701
- Lead Sponsor
- Northwell Health
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description celecoxib first, then placebo celebrex (celecoxib) 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 celebrex (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. celecoxib first, then placebo 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 Placebo first, then celecoxib 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.
- Primary Outcome Measures
Name Time Method Mean Percent Change in Papilloma Growth Rate at 12 Month Measurement Compared to Baseline 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
Name Time Method Percent of Patients With Positive Response to Treatment 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%. 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%. 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.
Correlation Between Mean Plasma Level of Celecoxib and Response. 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.
Effect of HPV 6 Versus HPV 11 on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50% 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.
Maintenance of Response Following Discontinuation of Celecoxib 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.
Trial Locations
- Locations (7)
University of Iowa
🇺🇸Iowa City, Iowa, United States
Eastern Virginia Medical School
🇺🇸Norfolk, Virginia, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
Sanford Health /USD
🇺🇸Sioux Falls, South Dakota, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States