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

Phase 2

Terminated

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

Interventions: Drug: gemcitabine hydrochloride
Drug: cisplatin
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis

Registration Number: NCT01611662

Lead Sponsor: Fox Chase Cancer Center

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 32

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (gemcitabine hydrochloride, cisplatin, surgery)	gemcitabine hydrochloride	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.
Treatment (gemcitabine hydrochloride, cisplatin, surgery)	therapeutic conventional surgery	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.
Treatment (gemcitabine hydrochloride, cisplatin, surgery)	laboratory biomarker analysis	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.
Treatment (gemcitabine hydrochloride, cisplatin, surgery)	cisplatin	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.

Primary Outcome Measures

Name	Time	Method
Pathological Complete Response Rate Following Chemotherapy Before Surgery	Up to 5 years	Pathological response rate following neoadjuvant chemotherapy was assessed by TNM staging at the time of radical cystectomy

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (2): Thomas Jefferson University, Kimmel Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States