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
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.
Interventional
Allocation: Randomized, Primary Purpose: Treatment
Nancy Lewis, MD
Principal Investigator
Fox Chase Cancer Center
United States: Federal Government
CDR0000365460
NCT00084578
March 2004
Name | Location |
---|---|
Fox Chase Cancer Center | Philadelphia, Pennsylvania 19111 |