Gene Expression Profiling in Predicting Chemotherapy Response in Patients with Localized, Muscle-Invasive Bladder Cancer

Inclusion Criteria

• Patients must have histologically proven urothelial carcinoma of the bladder; those with mixed histology, including a component of urothelial carcinoma, are eligible; small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded
• Patients must have stage cT2-T4a N0 M0 disease; clinical T stage is based on the transurethral resection of bladder tumor (TURBT) sample and imaging studies; patients must undergo cystoscopy and TURBT as part of the staging procedure within 56 days prior to registration; to exclude non-bulky/low-risk tumors and ensure adequate tissue for assessment, subjects must have documented muscle invasion with at least one of the following: * Disease measuring at least 5 mm on cross-sectional imaging or by endoscopic assessment; bladder thickening on imaging without definable tumor is not adequate; pathology verification of >= 0.5 cm of viable tumor (longest diameter) from the biopsy sample and represented on the submitted slides is also acceptable * The presence of tumor-associated hydronephrosis
• Patients must have staging scans with abdominal/pelvic computed tomography (CT) or magnetic resonance imaging (MRI) scan and CT scan or x-ray of the chest within 56 days prior to registration; if alkaline phosphatase is above the treating institution’s upper limit of normal (ULN), presence of suspicious bone pain, or if other clinical suspicion, a whole body bone scan is required within 56 days prior to registration
• Patients must have a Zubrod performance status of 0 or 1
• Patients must be 18 years of age or older
• Patients must not have received previous systemic cytotoxic chemotherapy for urothelial carcinoma
• Patients must not have received previous systemic anthracycline (intravesical anthracycline is allowed)
• Patients must not have peripheral neuropathy >= grade 2
• Patients must not have presence of class III or IV heart failure, according to New York Heart Association classifications, or a known left ventricular ejection fraction of less than 50%; Note: left ventricular ejection fraction (LVEF) evaluation by echocardiogram or multi-gated acquisition scan (MUGA) is not required prior to registration
• Patients must not have a clinically relevant hearing impairment > grade 2
• Calculated creatinine clearance >= 60 mL/min; the serum creatinine value used in the calculation must have been obtained within 28 days prior to registration; use the modified Cockcroft-Gault formula
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (or =< 2.5 x ULN with Gilbert’s disease) (obtained within 28 days prior to registration)
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2 x institutional ULN (obtained within 28 days prior to registration)
• Absolute neutrophil count (ANC) >= 1,500/mcL (obtained within 28 days prior to registration)
• Hemoglobin >= 9 g/dL (obtained within 28 days prior to registration)
• Platelets >= 100,000/mcL (obtained within 28 days prior to registration)
• Patients must not be known to have hypersensitivity to cisplatin, gemcitabine (gemcitabine hydrochloride), doxorubicin (doxorubicin hydrochloride), vinblastine (vinblastine sulfate), methotrexate or filgrastim/pegfilgrastim
• Patients must not have any incidence of or uncontrolled medical illness (e.g. active cardiac symptoms, active systemic infection, etc.) that would limit the patient’s ability to participate in the protocol
• Prestudy history and physical must be obtained within 28 days prior to registration
• Patients must not be pregnant or nursing; women/men of reproductive potential must agree to use an effective contraceptive method during and for 6 months after completing protocol treatment; a negative pregnancy test (either serum or urine) is required within 7 days prior to registration; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years; patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
• Patients must have tumor tissue from transurethral resection of the bladder tumor (TURBT) available for submission that is sufficient for COXEN testing and must agree to submission of 20 (10 micron) slides of formal-fixed paraffin embedded (FFPE) tissue, with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides; the diagnostic TURBT sample must have been obtained within 56 days prior to registration; all sections should be placed on "plus" slides, as is the standard procedure in most pathology units
• Patients must consent, if residual tumor is present at the time of cystectomy, to the submission of 20 (10 micron) unstained slides with 2 (5 micron) slides at the start and stop of the series (total of 22 unstained slides)
• Patients must consent to have voided urine (40-50 mL) submitted prior to initiating chemotherapy (pre-treatment) and after chemotherapy prior to surgery (post-treatment)
• Patients must consent to whole blood (2 x 10 mL) submitted prior to initiating chemotherapy
• Patients must agree to participate in the translational medicine studies
• Patients must be offered the opportunity to participate in the ultra pure Circulating Tumor Cells (upCTCs) study
• Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent prior to any study-related procedures in accordance with institutional and federal guidelines
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of Institutional Review Board approval for this study has been entered in the system