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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
North Shore Long Island Jewish Health System
ClinicalTrials.gov Identifier:
NCT00571701
First received: December 10, 2007
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

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 no 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.


Condition Intervention Phase
Recurrent Respiratory Papillomatosis
Drug: celebrex (celecoxib)
Drug: placebo capsules
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentered Randomized Study of Celebrex (Celecoxib) in Patients With Recurrent Respiratory Papillomatosis

Resource links provided by NLM:


Further study details as provided by North Shore Long Island Jewish Health System:

Primary Outcome Measures:
  • What is the efficacy of celebrex response relative to conventional endoscopy and surgical removal in reducing recurrence,and is improvement maintained when celecoxib therapy stops? [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Do any clinical characteristics (age of onset, gender, HPV type) predict response? [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Do molecular markers suggest inhibitions of COX-2 as mechanism of response? [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Does celebrex reduce persistence of HPV DNA or alter HPV expression. [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 62
Study Start Date: February 2008
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: early treatment
Patients randomized to start celecoxib 6 months after enrollment. Then cross over to placebo after 1 year.
Drug: celebrex (celecoxib)
Adults: 400 mg daily Pediatrics: 100 mg daily for weight between 12-25 kg or 200 mg daily for weight >25 kg
Other Name: Celebrex
Placebo Comparator: delayed treatment
Patients randomized to start placebo 6 months after enrollment. Cross over to 12 months of treatment with celecoxib after 1 year.
Drug: placebo capsules
Not relevant

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 persistence of latent HPV DNA, and to determine whether celecoxib is acting through inhibition of COX-2, in order to begin to determine mechanism of effects in vivo on RRP. 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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00571701

Locations
United States, Alabama
University of Alabama Birmingham
Birmingham, Alabama, United States, 35294
United States, California
UCSF Medical Center
San Francisco, California, United States, 94115
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, New York
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
United States, South Dakota
Sanford Health /USD
Sioux Falls, South Dakota, United States, 57104
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Virginia
Eastern Virginia Medical School
Norfolk, Virginia, United States, 23507
Sponsors and Collaborators
North Shore Long Island Jewish Health System
Investigators
Principal Investigator: Bettie M Steinberg, PhD Long Island Jewish Medical Center
  More Information

Publications:
Responsible Party: North Shore Long Island Jewish Health System
ClinicalTrials.gov Identifier: NCT00571701     History of Changes
Obsolete Identifiers: NCT00297999
Other Study ID Numbers: 1 U01 DC007946-01A2, U01DC007946, NIH grant U01DC007946-01A2
Study First Received: December 10, 2007
Last Updated: January 21, 2014
Health Authority: United States: Federal Government

Keywords provided by North Shore Long Island Jewish Health System:
HPV
RRP

Additional relevant MeSH terms:
Papilloma
Respiratory Tract Infections
Papillomavirus Infections
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Infection
Respiratory Tract Diseases
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Celecoxib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Central Nervous System Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 22, 2014