Gemcitabine Hydrochloride and Cisplatin Before Surgery in Treating Patients With Muscle Invasive Bladder Cancer

Study Overview
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Brief Summary
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The purpose of this research study is to find out what effects, good and/or bad, dose-dense (every 14 days) chemotherapy with gemcitabine (gemcitabine hydrochloride) and cisplatin given before surgery have on patients and their muscle invasive bladder cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the rate of complete response (pT0) at cystectomy following preoperative dose dense gemcitabine and cisplatin (DD GC) in patients with muscle invasive urothelial carcinoma of the bladder. SECONDARY OBJECTIVES: I. To assess the toxicity profile of DD GC when given in the neoadjuvant setting: To define the number of patients who complete all three cycles of treatment without dose reduction, and to describe the incidence of toxicity. II. To assess the 5 year overall and relapse free survival in patients who receive neoadjuvant DD GC. TERTIARY OBJECTIVES: I. To evaluate tissue specimens from patients to assess for molecular markers that correlate with clinical outcome. OUTLINE: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy. After completion of study treatment, patients are followed up for 5 years.

Official Title
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Phase II Trial of Neoadjuvant Dose Dense Gemcitabine and Cisplatin In Muscle Invasive Bladder Cancer

Conditions
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Distal Urethral Cancer, Proximal Urethral Cancer, Squamous Cell Carcinoma of the Bladder, Stage II Bladder Cancer, Stage III Bladder Cancer, Urethral Cancer Associated With Invasive Bladder Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: cisplatin
* Procedure: therapeutic conventional surgery
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically confirmed urothelial carcinoma of the bladder or urethra; patients with urothelial carcinoma of the prostatic urethra only may be included at primary investigator (PI) discretion; T-stage must be T2 to T4a; patients with radiographic N0 disease or N1 disease are eligible for the study; patients must not have radiographic evidence of metastatic disease; mixed histologies which are predominantly urothelial, such as with squamous or micropapillary differentiation, are allowed so long as there is no component of small cell histology; histology must be confirmed by a pathologist at an institution involved in this study Patients must be candidates for radical cystectomy with the goal of cure Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Leukocytes >= 3,000/mcL Absolute neutrophil count >= 1,500/mcL Platelets >= 100,000/mcL Total bilirubin =< institutional upper limit of normal (ULN) Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN Patients must have adequate renal function defined as creatinine clearance >= 50 mL/min; for eligibility, creatinine clearance may be either calculated using the Cockcroft-Gault formula or measured with 24 hour urine collection; note that 24 hour urine collection is required at baseline, but does not have to be used for eligibility if calculated clearance by Cockcroft-Gault is preferred; nephrostomy or ureteral stent placement in order to achieve adequate creatinine clearance is allowed Women of child-bearing potential (WOCBP) and men with a female partner who is a WOCBP must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting prior to beginning treatment and continuing until at least 3 months after last dose of chemotherapy and surgery; should a woman become pregnant or suspect she is pregnant while participating in this study or if a female partner of a man participating in this study becomes pregnant, the treating physician must be notified immediately; WOCBP must have a negative serum or urine pregnancy test within 7 days prior to initiating study treatment No other active malignancy Ability to understand and the willingness to sign written informed consent and Health Insurance Portability and Accountability Act (HIPAA) documents Exclusion Criteria: Patients who have had intravesicular therapy within 4 weeks of study entry, or those who have not recovered from adverse effects of such agents administered more than 4 weeks earlier Patients may not be receiving any investigational agents within 4 weeks of study entry History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or cisplatin or other agents used in the study Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible Patients who have undergone prior radiation to greater than or equal to 25% of the bone marrow within the past year are excluded Patients who have received any previous systemic chemotherapy or radiation therapy for urothelial carcinoma within 1 year of study entry are ineligible

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (gemcitabine hydrochloride, cisplatin, surgery)<br>Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy. | Drug: gemcitabine hydrochloride<br>* Given IV<br>* Other names: Gemzar;Drug: cisplatin<br>* Given IV<br>* Other names: DDP;Procedure: therapeutic conventional surgery<br>* Undergo radical cystectomy<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response Rate Following Chemotherapy Before Surgery | Pathological response rate following neoadjuvant chemotherapy was assessed by TNM staging at the time of radical cystectomy | Up to 5 years |