Phase IIb/III Chemoprevention Trial of Celecoxib to Prevent Recurrence of Superficial Bladder Cancer

Inclusion Criteria

Criteria:

- No concurrent radiotherapy

- No prior angioplasty

- No concurrent chemotherapy

- No concurrent oral or IV corticosteroids for more than 2 consecutive weeks or orally
inhaled corticosteroids for more than 4 consecutive weeks during any 6 month period
of the study

- Chronic nasally inhaled steroids allowed provided patient agrees to use mometasone
or, in countries where mometasone is not available, fluticasone

- No prior coronary bypass surgery

- At least 30 days since prior investigational medication

- No other prior malignancy within the past 5 years except:

- No prior pelvic radiotherapy

- Histologically proven superficial transitional cell carcinoma of the bladder at high
risk for recurrence, meeting 1 of the following staging criteria:

- Stage Ta (grade 3 OR multifocal OR at least 2 occurrences, including current tumor,
within the past 12 months)

- Stage T1 (any grade)

- Stage Tis

- Patients with Ta or T1 lesions must have undergone complete transurethral resection
of bladder tumor within the past 9 months

- No carcinoma involving the prostatic urethra or upper urinary tract

- Must have received the following prior to randomization:

- Induction course of BCG comprising 6 weekly intravesical doses (at least 4 doses if
BCG intolerant)

- Additional induction courses of BCG allowed

- Maintenance course of BCG comprising 3 weekly doses (at least 1 dose if BCG
intolerant)

- No evidence of disease by cystoscopy (with or without biopsy) and bladder cytology
prior to initiation of maintenance BCG

- Concurrent interferon allowed

- Zubrod 0-2 or ECOG 0-2

- WBC at least 3,000/mm^3

- Hemoglobin at least lower limit of normal

- Platelet count at least 125,000/Mm^3

- No significant bleeding disorder

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- SGOT and SGPT no greater than 1.5 times ULN

- No chronic or acute hepatic disorder

- Creatinine no greater than 1.5 times ULN

- No chronic or acute renal disorder

- Normal kidneys and ureters on imaging study within the past 9 months

- No active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis)

- No active pancreatitis

- No esophageal, gastric, pyloric channel, or duodenal ulceration that was diagnosed or
treated within the past 30 days

- No history of cardiovascular disease, including any of the following conditions:

- Stroke

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other medical or psychological condition that would preclude study participation

- No hypersensitivity or adverse reactions to sulfonamides, cyclooxygenase (COX)-2
inhibitors, salicylates, or other NSAIDs

- Nonmelanomatous skin cancer cured by excision

- Carcinoma in situ of the cervix

- Stage 0 chronic lymphocytic leukemia

- Other malignancy for which patient has no current evidence of disease, has received
no therapy within the past 6 months, has no concurrent or planned therapy, and has an
expected disease-free survival of at least 5 years

- No concurrent immunotherapy

- At least 2 weeks since prior aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs)
except cardioprotective dose (no greater than 100 mg/day) of aspirin

- No concurrent chronic NSAIDs except oral cardioprotective dose (no greater than 100
mg/day) of aspirin

- Concurrent chronic use is defined as a frequency of at least 3 times per week for
more than 2 consecutive weeks per year

- No other concurrent investigational drug

- No other concurrent systemic therapy

- No concurrent lithium or fluconazole

- No other concurrent hormonal therapy except hormone replacement (i.e., estrogen or
thyroid hormone replacement)

- Myocardial infarction

- Angina

- Congestive heart failure