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
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.
Drug: rosiglitazone maleate
Procedure: conventional surgery
Procedure: neoadjuvant therapy
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||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|
|Study Start Date:||March 2004|
|Study Completion Date:||April 2006|
|Primary Completion Date:||April 2006 (Final data collection date for primary outcome measure)|
- 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.
- 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).
- 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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00084578
|Principal Investigator:||Nancy Lewis, MD||Fox Chase Cancer Center|