RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of celecoxib may be an effective way to prevent the recurrence of bladder cancer.

PURPOSE: Randomized phase IIb/III trial to study the effectiveness of celecoxib in preventing disease recurrence in patients who have bladder cancer.

Condition	Treatment or Intervention	Phase
recurrent bladder cancer	Drug: celecoxib  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: cancer prevention intervention  Procedure: chemoprevention of cancer  Procedure: growth factor antagonist therapy	Phase II Phase III

Further Study Details: 

OBJECTIVES:

• Compare the time to recurrence after treatment with celecoxib vs placebo in patients with superficial transitional cell carcinoma of the bladder at high risk for recurrence.
• Correlate the modulation of one or more biomarkers with recurrence of bladder cancer and confirm the value of the marker(s) as a surrogate endpoint biomarker for bladder cancer and celecoxib.
• Determine the toxicity of celecoxib in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to center and presence of Tis disease (yes vs no). Patients are randomized to one of two arms.

• Arm I: Patients receive oral celecoxib twice daily.
• Arm II: Patients receive oral placebo twice daily. Treatment continues in both arms for 1-2 years in the absence of unacceptable toxicity, development of recurrent or invasive bladder carcinoma, or development of a second malignancy requiring radiotherapy or systemic therapy.

Quality of life is assessed at baseline and at week 54.

Patients are followed at 6 weeks and then every 12 weeks until the last randomized patient has been on the study for 1 year or until disease recurrence.

PROJECTED ACCRUAL: A total of 152 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Zubrod 0-2 OR
• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• 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

Hepatic:

• 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

Renal:

• 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

Gastrointestinal:

• 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

Other:

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

PRIOR CONCURRENT THERAPY: Biologic therapy:

• See Disease Characteristics
• No concurrent immunotherapy

Chemotherapy:

• No concurrent chemotherapy

Endocrine therapy:

• 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 other concurrent hormonal therapy except hormone replacement (i.e., estrogen or thyroid hormone replacement)

Radiotherapy:

• No prior pelvic radiotherapy
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• At least 30 days since prior investigational medication
• 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

Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States; Recruiting

Study chairs or principal investigators

Anita L. Sabichi, MD,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000068139; MDA-ID-99368; NCI-P00-0165; SC-NQ4-99-02-006; NCT00006124
Record last reviewed:  October 2003
Last Updated:  February 7, 2005
Record first received:  August 3, 2000
ClinicalTrials.gov Identifier:  NCT00006124
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08