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The purpose of this study is to compare patient tumor tissue before and after treatment with chemotherapy plus celecoxib. Investigators will look at gene expression, to see what effect celecoxib may have on tumor cells.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Celecoxib plus Gemcitabine/Cisplatin chemo | Experimental | Celecoxib plus Gemcitabine/Cisplatin neoadjuvant chemotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Celecoxib | Drug | Celecoxib (100 mg daily) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| mRNA expression in pre- and post-chemotherapy tissues | Up to four 21-day cycles of chemotherapy. | |
| Number and severity of adverse events | Until 30 days after last treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Pathological disease stage at cystectomy, including the rate of pT0 and the rate of < pT2. | At surgery, within 70 days after completing chemotherapy | |
| Two-year progression free survival | Up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Changes Cytokeratin 14 and phospho-histone H3 (proliferation markers) | Correlative Objective | Between baseline and treatment completion, up to 154 days |
| Changes in COX2 IHC staining | Correlative Objective |
Inclusion Criteria:
To exclude non-bulky/low-risk tumors, subjects must have documented muscle invasion with at least one of the following:
i. Disease measuring at least 10 mm on cross-sectional imaging. Bladder thickening on imaging, by itself, is not adequate.
ii. The presence of tumor-associated hydronephrosis.
Patients must have staging scans with abdominal/pelvic CT or MRI scan, and CT scan or x-ray of the chest within 56 days prior to registration. If the alkaline phosphatase is > 1.5 x upper limit of normal (ULN), there is a presence of suspicious bone pain, or if there is other clinical suspicion of bone metastases, a whole body bone scan is required within 56 days prior to registration.
Patients must have a Zubrod performance status of 0, 1 or 2.
Patients must be 18 years of age or older.
Patients must have adequate renal function as evidenced by calculated creatinine clearance ≥ 50 mL/min. The serum creatinine value used in the calculation must have been obtained within 28 days prior to registration.
Patients must have adequate hepatic function (within 28 days prior to registration), defined as:
i. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 2.5 x ULN with Gilbert's disease); and ii. SGOT (AST) ≤ 2 x institutional ULN; and iii. SGPT (ALT) ≤ 2 x institutional ULN.
Patients must have adequate hematologic function (within 28 days prior to registration), defined as:
i. Absolute neutrophil count (ANC) ≥ 1,500/μL; and ii. Hemoglobin ≥ 9 g/dL; and iii. Platelets ≥ 100,000/μL.
Patients must have tumor tissues from transurethral resection of the bladder tumor (TURBT) that is within 120 days of registration and available for submission. Tissue sample must be sufficient for IHC testing; that is,it must be sufficient tumor tissues for correlative science after pathologic diagnosis [i.e., enough tumor tissue to pass the staging criteria in 4c].
Patients must consent to the submission of FFPE blocks and/or unstained slides.
Exclusion Criteria:
Patients who have experienced a deep venous thrombosis or pulmonary embolus within the past 6 months must be on stable therapeutic anticoagulation to be enrolled to this study.
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| Name | Affiliation | Role |
|---|---|---|
| Aihua Edward Yen, MD | Baylor College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Baylor Clinic | Houston | Texas | 77030 | United States | ||
| Harris Health System - Smith Clinic |
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| ID | Term |
|---|---|
| D001749 | Urinary Bladder Neoplasms |
| ID | Term |
|---|---|
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000068579 | Celecoxib |
| D000093542 | Gemcitabine |
| D002945 | Cisplatin |
| ID | Term |
|---|---|
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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| Gemcitabine |
| Drug |
1,000 mg/m2 (IV), on Days 1 and 8 of each 21-day cycle. Up to 4 cycles. |
|
| Cisplatin | Drug | 70 mg/m2 (IV), on Day 1 of each 21-day cycle. Up to 4 cycles. |
|
| Two-year overall survival | Up to 2 years |
| Through treatment completion, up to 154 days |
| Changes in gene expression signatures in association with therapeutic response | correlative objective | Through treatment completion, up to 154 days |
| Houston |
| Texas |
| 77054 |
| United States |
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D001745 | Urinary Bladder Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
| D001555 |
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |