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
18 Years
N/A
Both
Bladder Cancer
Trial Information
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Principal Investigator
Nancy Lewis, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fox Chase Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000365460
NCT ID:
NCT00084578
Start Date:
March 2004
Completion Date:
Related Keywords:
- Bladder Cancer
- 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
- Urinary Bladder Neoplasms
- Carcinoma
- Carcinoma in Situ
Name | Location |
|---|---|
| Fox Chase Cancer Center | Philadelphia, Pennsylvania 19111 |
