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

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

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.

Study Overview

• Status: Terminated
• Conditions: Stage III Bladder Cancer; Distal Urethral Cancer; Proximal Urethral Cancer; Squamous Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer; Stage II Bladder Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: gemcitabine hydrochloride; Drug: cisplatin; Procedure: therapeutic conventional surgery

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University, Kimmel Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (gemcitabine hydrochloride, cisplatin, 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.	Other: laboratory biomarker analysis; Correlative studies; Drug: gemcitabine hydrochloride; Given IV; Other Names: Gemzar; gemcitabine; dFdC; difluorodeoxycytidine hydrochloride; Drug: cisplatin; Given IV; Other Names: CDDP; DDP; CACP; CPDD; Procedure: therapeutic conventional surgery; Undergo radical cystectomy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fox Chase Cancer Center
• Investigators: Principal Investigator: Elizabeth Plimack, Fox Chase Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2012
• Primary Completion (Actual): July 12, 2013
• Study Completion (Actual): January 22, 2019

Study Registration Dates

• First Submitted: May 30, 2012
• First Submitted That Met QC Criteria: June 4, 2012
• First Posted (Estimate): June 5, 2012

Study Record Updates

• Last Update Posted (Actual): July 29, 2019
• Last Update Submitted That Met QC Criteria: July 26, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urethral Diseases; Urinary Bladder Neoplasms; Urethral Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: ERP-GU-052 (Other Identifier: Fox Chase Cancer Center); NCI-2012-00906 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); IRB#12-015 (Other Identifier: Fox Chase Cancer Center)