Celecoxib as a Chemopreventive Agent in Current and Former Smokers - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00981201

Purpose

The purpose of this study is:

To examine the effect of celecoxib treatment on Ki-67 expression, a marker of cell proliferation, in the bronchial epithelium of current and former smokers.
To examine the toxicity associated with celecoxib administration.
To measure the effect of celecoxib treatment on arachidonic acid metabolites in the bronchial epithelium of current and former smokers.

Condition	Intervention	Phase
Smoking Prevention	Drug: Celecoxib Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Parallel Assignment, Safety/Efficacy Study
Official Title:	A Randomized, Double-Blind Study of the Biological Effects and Tolerability of Celecoxib as a Chemopreventive Agent in Current and Former Smokers

Resource links provided by NLM:

MedlinePlus related topics: Cancer Smoking

Drug Information available for: Celecoxib

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

The change of the proliferation marker Ki-67. [ Time Frame: From baseline to 3-month visit. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The changes in tissue COX-2 expression, lavage PGE2 levels, and genetic markers such as LOH, chromosome instability, and chromosome polysomy. [ Time Frame: 3-months and 6-months ] [ Designated as safety issue: No ]

Enrollment:	219
Study Start Date:	November 2001
Study Completion Date:	September 2009
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Celecoxib + Placebo: Experimental	Drug: Celecoxib Months 1-3: As of October, 2003, the starting dose for celecoxib will be 400 mg by mouth twice daily. (Note: Prior to October, 2003, the starting dose for celecoxib was 200 mg by mouth twice daily.) Drug: Placebo Months 4-6: By mouth twice daily.
Celecoxib + Celecoxib: Experimental	Drug: Celecoxib Months 1-3: As of October, 2003, the starting dose for celecoxib will be 400 mg by mouth twice daily. (Note: Prior to October, 2003, the starting dose for celecoxib was 200 mg by mouth twice daily.) Drug: Celecoxib Months 4-6: As of October, 2003, the starting dose for celecoxib will be 400 mg by mouth twice daily. (Note: Prior to October, 2003, the starting dose for celecoxib was 200 mg by mouth twice daily.)
Placebo + Celecoxib: Active Comparator	Drug: Celecoxib Months 4-6: As of October, 2003, the starting dose for celecoxib will be 400 mg by mouth twice daily. (Note: Prior to October, 2003, the starting dose for celecoxib was 200 mg by mouth twice daily.) Drug: Placebo Months 1-3: By mouth twice daily.
Placebo + Placebo: Placebo Comparator	Drug: Placebo Months 1-3: By mouth twice daily. Drug: Placebo Months 4-6: By mouth twice daily.

Detailed Description:

COX-2 is an enzyme thought to be involved in the development of some cancer. Celecoxib is a COX-2 inhibitor.

Before treatment begins, participants will have a bronchoscopy (tissue sample from the lung). This is taken to see if different elements (biomarkers) in the tissue can predict which individuals are at higher risk for developing cancer. In a bronchoscopy a tube will be placed through the nose into the lung (while under sedation) to remove tissue samples for laboratory analysis (biopsy). Cells will also be collected during the bronchoscopy by spraying the lungs with a small amount water and then removing the water (bronchial lavage, bronchial washing). In addition, a sputum sample will be taken and the inside of the cheek will be scraped (buccal sample).

A complete physical exam will be performed before beginning treatment and at 1, 2, 3, 4, 5, and 6 months. During these visits, participants will be asked questions about tobacco/alcohol exposure. Participants will have blood taken before beginning treatment and at 1, 3, 4, and 6 months. Urine samples will be taken before beginning treatment and at 3 and 6 months. The research nurse will also ask participants about any adverse signs or symptoms that they have experienced. Participants who smoke will be encouraged to stop smoking. Sources for assistance to stop smoking will be provided for all study participants who continue to smoke.

In this study, participants will be randomly picked (as in the toss of a coin) to be in one of four treatment groups. Treatment in this study will last 6 months. Participants in the first group will receive a placebo during all 6 months. A placebo is a substance that looks like the study drug but is inactive. Participants in the second group will receive a placebo during Months 1-3 and Celecoxib during Months 4-6. Participants in the third group will receive Celecoxib during Months 1-3 and placebo during Months 4-6. Participants in the fourth group will receive Celecoxib during all 6 months. Neither the participant nor the participant's doctor will know to which treatment group the participant was assigned. Participants have an equal chance of being assigned to any of these groups.

Participants will take 2 capsules twice a day for the 6-month treatment period. The capsule could be either a placebo or the study drug.

At 3 and 6 months, participants will have a physical exam, blood tests, and a bronchoscopy. Participants should take their study medication with a sip of water 2 hours before each bronchoscopy with a sip of water. Sputum and buccal samples will also be taken at these times. The research nurse will ask participants questions about changes and/or additions to the medications.

This is an investigational study. The use of Celecoxib in the prevention of lung cancer is investigational. Up to 250 individuals will take part in this study. All will be enrolled at the M. D. Anderson.

Eligibility

Ages Eligible for Study:	18 Years to 74 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Participants must be 18-74 years old.
Participants must have at least a 20 pack-year history of smoking.
Participants may have had a prior laryngeal cancer (Stage I or II) that was completely resected or rendered disease-free by radiation therapy, or a prior lung cancer (Stage I NSCLC) that was completely resected, without radiotherapy. Participants must have been clinically free of any cancer for at least 6 months.
Participants must have no contraindications for undergoing bronchoscopy.
Participants must have no active pulmonary infections.
Participants must not be taking inhaled steroids or oral non-steroidal anti-inflammatory drugs on a regular basis. (Low dose aspirin <= 81 mg/day is allowed.)
Participants must have the following blood levels: total granulocyte count > 1500; platelet count > 100,000; total bilirubin <= 1.5 mg %; and creatinine <= 1.5 mg %.
Participants must complete the pretreatment evaluation and must consent to bronchoscopy and to endobronchial biopsy for documentation of histologic status.
Participants must sign a study-specific informed consent form.

Exclusion Criteria:

Participants with active gastric or duodenal ulcers or a history of ulcers requiring prophylactic H2 blockers.
Participants with active pulmonary infections or recent history of pulmonary infection (within 1 month).
Participants receiving inhaled steroid therapy on a regular basis.
Participants with acute intercurrent illness, or participants who had surgery within the preceding 4 weeks unless they have fully recovered.
Participants requiring chronic ongoing treatment with NSAIDs.
Participants who are allergic to aspirin or sulfanamides.
Participants with history of stroke, transient ischemic attack, uncontrolled hypertension, and/or angina pectoris.
Participants who are pregnant and/or breast-feeding.
Participants (men or women) of childbearing potential who are not using an effective method of contraception.
History of cardiovascular diseases that might include one of the following: myocardial infarction, angina, coronary angioplasty, congestive heart failure, stroke, or coronary bypass surgery.
Diagnosis of diabetes
History of deep venous thrombosis, pulmonary embolism, systemic lupus erythematous, family history of protein S or C deficiencies, prior heparin-induced thrombocytopenia, or known Factor V Leiden mutation.
Family history of premature CAD. This is defined as individuals with either: 1) father with MI prior to age 55, or 2) mother with MI prior to age 60.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00981201

Locations

United States, Texas
U.T. M.D. Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Jonathan M. Kurie, MD

U.T. M.D. Anderson Cancer Center

More Information

No publications provided

Responsible Party:	U.T. M.D. Anderson Cancer Center ( Jonathan M. Kurie, MD / Professor )
Study ID Numbers:	ID00-230
Study First Received:	September 18, 2009
Last Updated:	September 21, 2009
ClinicalTrials.gov Identifier:	NCT00981201 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Smoking
Cancer Prevention
Celecoxib
Celebrex
Placebo

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Celecoxib
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Physiological Effects of Drugs
Enzyme Inhibitors
Pharmacologic Actions
Smoking
Habits

Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010