Celecoxib in Preventing Cancer in Patients With Oral Leukoplakia and/or Head and Neck Dysplasia

Celecoxib is being studied in precancerous lesions of the head and neck in part because, it
has been shown to prevent the progression of another type of precancerous polyps (a type of
abnormal growth) in patients at high risk for colorectal cancer. There are, however, no
published studies yet looking at this drug in humans for the prevention of head and neck
cancers. The U.S. Food and Drug Administration has approved celecoxib for arthritis and the
prevention of polyps in patients with familial adenomatous polyposis (a type of precancerous
syndrome in some families that can lead to colon cancer).

This study is being done to find out several things:

- Is celecoxib, also known by the trade name Celebrex ®, effective in reducing the
expression of precancerous markers (biological signals for specific cellular activities)
in oral leukoplakia and dysplasia (abnormal growth) of the oral mucosa?

- Is celecoxib effective in reducing the size of oral leukoplalda lesions and/or presence
of dysplasia?

- Does the reduction in precancerous markers correspond with reduction of oral leukoplalda
and/or presence of dysplasia?

- What are the side effects of celecoxib in this patient population?

Inclusion Criteria:

- Subjects will be ≥ 18 years.

- Subjects will have oral leukoplakia on clinical examination and/or more than one
previous HNSCC with dysplasia histologically proven on random biopsy within 6 months
at the time of entry.

- Patients who have had surgical treatment for a previous HNSCC, stage I-III, will be
eligible for enrollment if they are cancer-free ≥ 9 months at the time of entry.
Patients with CIS or new leukoplakia will be immediately eligible if they are more
then 9 months from treatment of a prior carcinoma.

- Leukoplakia lesions must be ≥ 0.5 cm in at least one dimension to be considered
measurable. Measurable lesions are not required for entry.

- The ECOG performance status will be ≤ 2. (See Appendix B for ECOG performance status.)

- The life expectancy will be ≥12 months.

- Subjects will have adequate organ function with a platelet count of >100,000, ANC >
1500, PT and PTT < 1.5 X ULN, creatinine <1.5, urine protein <2+, and total bilirubin
and liver transaminases <1.5 X ULN.

- Premenopausal women will be required to use a reliable method of birth control
throughout the course of therapy.

- Subjects will provide written, voluntary informed consent

Exclusion Criteria:

- Patients who have had surgical treatment for a previous HNSCC, stage I-III, will not
be eligible for enrollment if they are cancer-free < 9 months at the time of entry.

- Subjects with contraindication to nasopharyngoscopy and biopsy will not be enrolled.

- Significant comorbidities, including known coronary artery disease, angina, history of
myocardial infarction, congestive heart failure of at least grade 2 according to the
New York Heart Association Criteria, advanced COPD requiring use of home oxygen,
active alcohol abuse, bleeding diathesis, any history of gastrointestinal ulcer, acute
or chronic renal insufficiency, or acute or chronic liver disease, will preclude
enrollment in the trial.

- Enrollment in the trial will be limited to patients who are free from current tobacco
use. If the patient has a history of previous tobacco use, they Must be abstinent for
at least 1 month prior to enrollment and meet the criteria established by the Food and
Drug Administration for assessing smoking cessation, i.e. have not taken even a puff
or taste of tobacco, including cigarette, cigar, pipe, chewing tobacco or other
tobacco products, in the past 4 weeks.

- Any active malignancy, except non-melanoma skin cancer, will preclude enrollment.

- Persons who have taken full-dose aspirin, NSAIDs, COX-2 inhibitors and
systemicallyabsorbed steroids, including inhaled steroids and nasal steroids other
than mometazone, at least 3 times per week for 2 or more consecutive weeks within 3
months of enrollment will be excluded. Persons who have taken retinoids or selenium
within 3 months of enrollment, or who have a history of anaphylactoid reaction to
aspirin, NSAIDs or COX- 2 inhibitors will not be enrolled.

- Persons taking ACE inhibitors will not be enrolled. Diuretics for CHF, or treatment
with lithium or fluconazole will also preclude enrollment. Patients on coumadin will
be required to have PT/INR monitoring BIW after starting celecoxib, until the patient
is on a stable dose of coumadin for 7 days, and must have no contraindication to
holding the coumadin for study biopsies.

- Pregnant, lactating women or premenopausal women with a positive f3HCG will not be
enrolled in the study.