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 - Full Text View

Sponsors and Collaborators:	Fox Chase Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00084578

Purpose

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.

Condition	Intervention
Bladder Cancer	Drug: celecoxib Drug: rosiglitazone maleate Procedure: conventional surgery Procedure: neoadjuvant therapy

Genetics Home Reference related topics: bladder cancer

MedlinePlus related topics: Bladder Cancer Cancer

Drug Information available for: Celecoxib 4-(5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide Rosiglitazone Rosiglitazone Maleate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

March 2004

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00084578

Locations

United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497

Sponsors and Collaborators

Fox Chase Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Nancy Lewis, MD

Fox Chase Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000365460, FCCC-03018
Study First Received:	June 10, 2004
Last Updated:	October 12, 2008
ClinicalTrials.gov Identifier:	NCT00084578
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Celecoxib
Cystocele
Urinary Bladder Diseases
Urinary Bladder Neoplasms
Urogenital Neoplasms
Carcinoma, Transitional Cell
Urologic Neoplasms

Transitional cell carcinoma
Carcinoma
Urologic Diseases
Rosiglitazone
Urinary tract neoplasm
Neoplasms, Glandular and Epithelial
Bladder neoplasm

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site

Hypoglycemic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009