Recurrent Respiratory PapillomatosisPhase 2NCT00571701
Study of Celebrex (Celecoxib) in Patients With Recurrent Respiratory Papillomatosis
A Phase 2 study testing celebrex (celecoxib) in people with Recurrent Respiratory Papillomatosis, run by Northwell Health at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Recurrent Respiratory Papillomatosis
- What is being tested?
- celebrex (celecoxib)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 7 sitesUnited States
- Study dates
- Feb 2008to Jan 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Alabama Birmingham
Birmingham, Alabama, 35294
University of Iowa
Iowa City, Iowa, 52242
Vanderbilt University
Nashville, Tennessee, 37232
Long Island Jewish Medical Center
New Hyde Park, New York, 11040
Eastern Virginia Medical School
Norfolk, Virginia, 23507
UCSF Medical Center
San Francisco, California, 94115
Sanford Health /USD
Sioux Falls, South Dakota, 57104
About this study
Official title: A Multicentered Randomized Study of Celebrex (Celecoxib) in Patients With Recurrent Respiratory Papillomatosis
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.
Read the 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.
- Conditions
- Recurrent Respiratory Papillomatosis
- Being tested
- celebrex (celecoxib), placebo
- Keywords
- HPV, RRP
- Medical subject headings
- Recurrent respiratory papillomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
celebrex (celecoxib)Drug
Also called Celebrex
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
placeboDrug
similar appearing capsules containing inert ingredients
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: celebrex (celecoxib); Drug: placebo |
| 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. Receives: Drug: celebrex (celecoxib); Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 12 months
Secondary outcomes (6)
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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: End of first treatment period (month 12) to end of second treatment period (month 24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2007 (estimated)
- Study startFeb 2008
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Respiratory PapillomatosisStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Sponsor
- Investigators
- Bettie M Steinberg, PhD, Principal investigator, Long Island Jewish Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00571701
- Sponsor's protocol ID
- 1U01DC007946-01A2
- Other IDs
- 1U01DC007946-01A2
- Status last verified
- Mar 2017
- First submitted
- 10 Dec 2007
- Last updated
- 15 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 16144915
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentered Randomized Study of Celebrex (Celecoxib) in Patients With Recurrent Respiratory Papillomatosis
- ClinicalTrials.gov ID
- NCT00571701
- Acronym / sponsor ID
- 1U01DC007946-01A2
- Conditions
- Recurrent Respiratory Papillomatosis
- Keywords
- HPV, RRP
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- 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
- Study start
- Feb 2008
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 12 Dec 2007 (estimated)
- Results
- Posted 23 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| celecoxib first, then placebo | Active comparator | Drug: celebrex (celecoxib), Drug: placeboPatients 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 | Drug: celebrex (celecoxib), Drug: placeboPatients 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. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| celebrex (celecoxib)Also: CelebrexAdults: 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 | Drug | Placebo first, then celecoxib, celecoxib first, then placebo |
| placebosimilar appearing capsules containing inert ingredients | Drug | Placebo first, then celecoxib, celecoxib first, then placebo |
Primary outcome
Mean Percent Change in Papilloma Growth Rate at 12 Month Measurement Compared to Baseline
Time frame: 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.
6 secondary outcomes
Percent of Patients With Positive Response to Treatment
Time frame: Baseline to 12 months
Effect of Gender on Percent of Patients With Reduction in Papilloma Growth Rate Greater Than 50%.
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%.
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%
Time frame: Baseline to 12 months
Correlation Between Mean Plasma Level of Celecoxib and Response.
Time frame: Baseline to 12 months
Maintenance of Response Following Discontinuation of Celecoxib
Time frame: End of first treatment period (month 12) to end of second treatment period (month 24)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16144915Wu 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bettie M Steinberg, PhD principal investigator
Long Island Jewish Medical Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing celebrex (celecoxib) in people with Recurrent Respiratory Papillomatosis, run by Northwell Health at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Percent Change in Papilloma Growth Rate at 12 Month Measurement Compared to Baseline (time frame: Baseline to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00571701, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2017.