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

NCT ID: NCT00571701

Last Updated: 2017-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2015-01-31

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.

Conditions

Recurrent Respiratory Papillomatosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

celebrex (celecoxib)

Intervention Type: 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

placebo

Intervention Type: DRUG

similar appearing capsules containing inert ingredients

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.

Group Type: PLACEBO_COMPARATOR

celebrex (celecoxib)

Intervention Type: 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

placebo

Intervention Type: DRUG

similar appearing capsules containing inert ingredients

Interventions

celebrex (celecoxib)

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

Intervention Type: DRUG

placebo

similar appearing capsules containing inert ingredients

Intervention Type: DRUG

Other Intervention Names

Celebrex

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Deafness and Other Communication Disorders (NIDCD)

NIH

Sponsor Role: collaborator

University of Iowa

OTHER

Sponsor Role: collaborator

Eastern Virginia Medical School

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: collaborator

Vanderbilt University

OTHER

Sponsor Role: collaborator

Sanford Health

OTHER

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: collaborator

Northwell Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bettie M Steinberg, PhD

Role: PRINCIPAL_INVESTIGATOR

Long Island Jewish Medical Center

Locations

University of Alabama Birmingham

Birmingham, Alabama, United States

UCSF Medical Center

San Francisco, California, United States

University of Iowa

Iowa City, Iowa, United States

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Sanford Health /USD

Sioux Falls, South Dakota, United States

Vanderbilt University

Nashville, Tennessee, United States

Eastern Virginia Medical School

Norfolk, Virginia, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 16144915 (View on PubMed)

Other Identifiers

1U01DC007946-01A2

Identifier Type: NIH

Identifier Source: secondary_id

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1U01DC007946-01A2

Identifier Type: NIH

Identifier Source: org_study_id

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NCT00297999

Identifier Type: -

Identifier Source: nct_alias