Celecoxib and Rosiglitazone in Treating Patients Who Are Undergoing Cystoscopic Surveillance for Early-Stage Noninvasive Carcinoma of the Bladder or Radical Cystectomy for Muscle-Invasive Carcinoma of the Bladder

Study Overview
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Brief Summary
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RATIONALE: Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor. Rosiglitazone may help tumor cells develop into normal bladder cells. PURPOSE: This randomized clinical trial is studying how well giving celecoxib together with rosiglitazone works in treating patients who are undergoing cystoscopic surveillance (screening) for early-stage noninvasive (carcinoma in situ) carcinoma (cancer) of the bladder or radical cystectomy for muscle-invasive carcinoma (cancer has spread into the muscle layer of bladder tissue) of the bladder.

Detailed Description
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OBJECTIVES: Primary Determine whether rosiglitazone and celecoxib, administered alone or in combination, cause changes in the expression of effector molecules, peroxisome proliferator-activated receptor-γ (PPAR-γ) and cyclo-oxygenase-1 (COX-1), in patients with early-stage non-invasive carcinoma of the bladder undergoing cystoscopic surveillance or in patients with muscle-invasive carcinoma of the bladder undergoing radical cystectomy. Secondary Determine whether these regimens result in changes in the expression of downstream effector molecules that mediate cellular proliferation and apoptosis in these patients. Determine the relationship between tissue levels of biomarkers of drug effect, proliferation, and apoptosis and the systemic biomarkers of response to treatment, in terms of COX-2 activity and the levels of the endogenous PPAR-γ ligand, in patients treated with these regimens. Determine the toxicity of these regimens in these patients. Determine the frequency of recurrence and the time to progression in patients undergoing cystoscopic surveillance. OUTLINE: This is a randomized, pilot, cohort study. Patients are assigned to 1 of 2 cohorts according to disease stage (Ta, Tis, T1, N0, M0 vs T2-4, NX, M0). Stage 1: Cohort 1: Patients receive oral celecoxib twice daily and oral rosiglitazone once daily for 1 year in the absence of disease progression or unacceptable toxicity. Cohort 2: Patients receive oral celecoxib twice daily and oral rosiglitazone once daily for 14 days. Patients then undergo cystectomy. Stage 2: Patients are randomized into 1 of 2 treatment arms. Arm I: Cohort 1: Patients receive oral celecoxib twice daily for 1 year in the absence of disease progression or unacceptable toxicity. Cohort 2: Patients receive oral celecoxib twice daily for 14 days. Patients then undergo cystectomy. Arm II: Cohort 1: Patients receive oral rosiglitazone once daily for 1 year in the absence of disease progression or unacceptable toxicity. Cohort 2: Patients receive oral rosiglitazone once daily for 14 days. Patients then undergo cystectomy. Patients in cohort 1 (in both stages) undergo cystoscopic surveillance every 3 months. PROJECTED ACCRUAL: A total of 120 patients (20 per cohort in study stage 1; 40 per treatment arm [20 per cohort in each arm] in study stage 2) will be accrued for this study within 12-18 months.

Official Title
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A Randomized Trial of Celecoxib and Rosiglitazone, Alone and in Combination, in Patients With Early Stage Non-Invasive Bladder Carcinoma Undergoing Cystoscopic Surveillance and in Patients With Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy

Conditions
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Bladder Cancer

Intervention / Treatment
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* Drug: celecoxib
* Drug: rosiglitazone maleate
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically and clinically confirmed bladder cancer Cohort 1 Papillary transitional cell carcinoma of the urinary bladder Stage Ta or T1 (grade 1 or 2), N0, M0 disease Must have undergone complete transurethral resection of the bladder within the past 28 days AND/OR Carcinoma in situ of the urinary bladder Stage Tis, N0, M0 disease Must have undergone biopsy within the past 28 days No histological and pathological evidence of invasion of the underlying muscle (stage T2) Cohort 2 Muscle-invasive papillary transitional cell carcinoma of the urinary bladder Stage T2-4, NX, M0 disease Intending to undergo radical cystectomy Must have had an upper tract (ureter and renal pelvic) evaluation by intravenous pyelogram, CT scan, or MRI that proved normal within the past year PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic WBC > 4,000/mm^3 Platelet count > 100,000/mm^3 Hepatic Bilirubin < 2 times upper limit of normal (ULN) SGOT and SGPT < 3 times ULN Renal Creatinine ≤ 2.5 mg/dL Other No other malignancy within the past 3 years except non-invasive bladder cancer, adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix No history of uncontrolled peptic ulcer disease No history of unexplained hypoglycemia No known sensitivity to celecoxib or rosiglitazone No allergy to sulfonamides No history of asthma, urticaria, or allergic reaction after taking aspirin or other NSAIDs No underlying uncontrolled medical illness Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy At least 3 months since prior intravesical BCG Chemotherapy No prior intravesical or systemic chemotherapy Endocrine therapy No concurrent insulin Radiotherapy Not specified Surgery See Disease Characteristics Other At least 2 weeks since prior use of non-steroidal anti-inflammatory drugs (NSAIDs) (including COX-2 inhibitors) for more than 3 consecutive days except low-dose (81 mg) aspirin No concurrent beta-blockers No concurrent NSAIDs No other concurrent oral hypoglycemic agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: celecoxib|nan|
|Drug: rosiglitazone maleate|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage 0 bladder cancer, stage I bladder cancer, stage II bladder cancer, stage III bladder cancer, stage IV bladder cancer, transitional cell carcinoma of the bladder